Chemotherapy on Harding-Passey melanoma with gladenine. Part I. The effect of Gladenine, an oncolytic antibiotic produced by a newly discovered fungus, Paecilomyces todicus, nov. sp. was investigated on Harding-Passey, hard tumor, melanoma. A long-term screening technique was used in the investigation. 15 mg/100 gm. wt/mouse was injected I.P. starting 10-14 days after transplant, when all tumors were well pronounced, and continuing for 18-34 days. The majority of mice did not lose weight. Tumors were absent on the average in about 33% of the mice and average T/C was .16. Combining Cladenine with Hydrazine sulfate, either 1.5 mg. or 2.5 mg./100 gm. wt./mouse, using the same screening technique, resulted in 60-100% of mice free of tumors, and still remaining so several months later. Average T/C was .06. Combined therapy with Gladenine and Hydrazine sulfate at 3.75 mg./100 gm. wt./mouse gave less satisfactory results. Repeated screening tests using the same long term techniques, gave similar or identical results. It appears that Harding-Passey melanoma is susceptible to the chemotherapy of Gladenine alone and/or combined with small doses of Hydrazine sulfate.


Hand skeletal development among Ecuadorians living under conditions of iodine deficiency and endemic goiter. Hand radiographic assessment has revealed the pattern of skeletal growth and maturation among Ecuadorian Indian villagers where iodine deficiency has resulted in an endemia of goiter and cretinism. This is intended to provide base line information for future attempts to learn about physical impairment among people living under inadequate iodine nutriture.


Model for initial vascular patterns in melanoma transplants. In this paper we present a simple mathematical model that adequately accounts for at least the initial vasculature that is established in a melanoma transplant. It is assumed that the tumor produces a substance (tumor angiogenesis factor--TAF) that elicits capillary sprouts from the vascular bed of the host. These sprouts then invade the tumor along the gradient of TAF and cross-connect forming a vascular pathway that is similar to the experimental patterns observed in a hamster cheek pouch. This model is then extended to include the migration of loops. The rupture and formation of sprouts from these loops is assumed to depend on the strength of the stimulus (TAF). Under the assumption that the production of TAF is significantly reduced in a neighborhood of an established vessel, the network formed by the vessels in the tumor corresponds to the observed arboreal patterns.


Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. The frequency of HLA-A3 and HLA-B14 antigens was significantly higher in a series of 51 patients with idiopathic haemochromatosis than in a control group, being respectively 78-4 versus 27-0% and 25-5 versus 3-4%. This finding strongly supports the suggestion that idiopathic haemochromatosis is a genetic disease and suggests that the gene(s) responsible for the disease may be linked to the histocompatibility genes.


Effect of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome. The influence of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome was studied in 29 patients. After a period on a normal diet (10 MJ) an intravenous infusion of 40% glucose (8-4 MJ) together with a 1-6 MJ oral diet for two days resulted in an increment in plasma bilirubin concentration of 127 +/- 18% (mean +/- SEM) above the basal level. Both the administration of intravenous Intralipid 20% and the return to a normal diet caused a prompt reversal of this glucose effect. An increment of 135 +/- 10% in plasma bilirubin concentration was obtained when a standard "fasting" diet (1-6 MJ) was given for two days. When the lipid content of this "fasting" diet was increased from 33% to 85%, the rise in plasma bilirubin was only 49 +/- 19%. A 10 MJ oral diet for three days, which contained most of its energy content as carbohydrate and only 0-6% as lipid, produced a 76 +/- 12% increase in plasma bilirubin concentration. When the lipid content of the diet was increased to 9% of the energy intake no significant change from the basal level was observed. These findings support the hypothesis that the hyperbilirubinaemia associated with both carbohydrate feeding and fasting is attributable, at least in part, to lipid withdrawal. Although a restricted dietary intake or the parenteral administration of lipid-free solutions has a marked effect on the hyperbilirubinaemia of patients with Gilbert's syndrome, normal daily variation in dietary composition is unlikely to cause a significant change. The influence of different feeding regimes on neonatal hyperbilirubinaemia requires investigation.


Altered elimination of antipyrine in patients with acute viral hepatitis. The plasma half-life and clearance of antipyrine was investigated in patients during the acute phase and again during the recovery phase of viral hepatitis. Each patient served as his own control, thereby eliminating genetic factors and minimising environmental factors that cause large interindividual variations in antipyrine elimination rates. Liver function tests, antipyrine, half-life, plasma clearance, and the apparent volume of distribution were determined in the acute and recovery period. It was found that the appaarent volume of distribution of antipyrine did not change in five of six patients as they recovered. Five of the six patients showed prolonged plasma half-lives and decreased plasma clearance of the drug at the time of acute illness and these parameters reached normal values during recovery. The plasma half-life and clearance of the drug did not correlate with biochemical indices of liver function in the recovery phase. This demonstration supports the concept that drug metabolism is frequently impaired in liver disease.


Effect of diazepam and hyoscine butylbromide on response to secretin and cholecystokinin-pancreozymin in man. Ten subjects received secretin and cholecystokinin or, in duplicate tests, the two hormones together with either diazepam or diazepam plus hyoscine butylbromide in order to determine whether these drugs, which are often used during retrograde endoscopic cannulation of the pancreatic duct, affect pancreatic and biliary secretion in response to the hormones. Diazepam with hyoscine butylbromide reduced the secretion of trypsin into the duodenum and delayed the appearance of both trypsin and bilirubin in duodenal aspirate. These effects must be taken into account when interpreting pancreatic and biliary responses measured during direct cannulation of the pancreatic duct.


Small intestinal permeability. 1. Effects of ischaemia and exposure to acetyl salicylate. Permeability of the small intestinal mucosa was estimated using a perfusion technique after either a period of ischaemia or exposure to acetyl salicylate. It was shown that these procedures increased the passive permeability of the mucosa to macromolecules while maintaining normal mucosal selectivity. Histologically, there was derangment of the epithelial cell layer of the villous tips without damage to the epithelial basement membrane or subepithelial structures. It is concluded that the epithelial cell layer is purely limiting with no selective function and that the role of selectivity must be ascribed to either or both of the other mucosal barriers, the capillary and the epithelial basement membrane.


Effects of 13-nle-motilin on the electrical and mechanical activity of the isolated perfused canine stomach and duodenum. Synthetic 13-norleucine-motilin (13-nle-motilin), structural and biological analogue of the naturally-occurring duodenal polypeptide, motilin, is known to stimulate antral and duodenal motor activity in vitro, but delays gastric emptying in man. In this study the direct actions of the synthetic polypeptide on myoelectrical activity and intraluminal pressure have been studied in the isolated vascular-perfused canine stomach and duodenum. 13-nle-motilin increased intraluminal pressure in the pylorus and duodenum, and dose-response analysis showed the duodenum to be twice as sensitive as the pylorus to the polypeptide. Pressure changes in the antrum were small and not dose-related, but, whereas the basic electrical rhythm in the duodenum was not altered, slow wave frequency, rhythm, and propagation in the antrum were disturbed. Electronic analysis of the duodenal spike increase which accompanied pressure rises demonstrated correlations between increases in spikes, intraluminal pressure, and dose. These results show that the direct effect of the polypeptide on adjacent organs may explain the combination of increased motor activity with delayed gastric emptying as a consequence of disturbance in the co-ordination between antrum, pylorus, and duodenum.


Serum pyridoxal in patients with gastric pathology. Fasting serum pyridoxal was assayed by an automated microbiological system in 60 patients investigated for dyspepsia, patients with active peptic ulceration being excluded from the study. Gastritis was present in 30 patients, gastric carcinoma in 16, six patients had benign polyps, and, in eight patients, radiology, endoscopy, and biopsy failed to shown any abnormality. Of the 52 patients with gastric pathology, 44 had a low serum pyridoxal.


Evaluation of specific value of endoscopic biopsies and brush cytology for malignancies of the oesophagus and stomach. The value of multiple biopsies and brush cytology at oesophago-gastroscopy was assessed in relation to macroscopy and localization on 100 verified tumours in a prospective study. The cumulative accuracy achieved was 96%. This was significantly better (P less than 0-01) than that of biopsy (83%) and of cytology (85%). While the reliability of both procedures was not significantly different in malignancies of the oesophagus, the gastric body, and the antrum, cytoloty was significantly more accurate in cancers of the cardia (90% and 55% respectively, P less than 0-05). Cytology was also more reliable in stenosing tumours (92%/72%,P less than 0-05). In polypoid malignancies a positive but not significant trend was found in favour of multiple biopsies (94%/64%). One of the two early cancers was only diagnosed by cytology. The results confirm the high diagnostic accuracy of multiple endoscopic biopsies combined with brush cytology and demonstrate the value of cytology in stenosing tumours, especially in those of the cardia.


Capillariids (Nematoda: Capillariidae) from passeriform birds of Nepal). A total of 83 hosts of the order Passeriformes from Nepal were examined for nematodes. Nine of them were found to be infected with 4 nematode species, Capillaria exilis, C. ovopunctata, Capillaria sp. and Thominx rigidula. The last species is redescribed in detail. Three of the definitive hosts are new for the above-mentioned nematode species and this is the first recorded from Nepal.


Variability of hard parts of opisthaptor of two species of Gyrodactylus nordmann, 1832 (Monogenoidea) from Phoxinus Phoxinus (L.). The morphological and metrical variability of hard parts of opisthaptor was studied in the representatives of local populations of Gyrodactylus aphyae Malmberg, 1957 and G. macronychus Malmberg, 1957. The changes within the range of variability, which were observed during the year, correspond to regular and periodical changes in the environmental temperatures. The hard parts of opisthaptor were much smaller in specimens occurring during warm seasons than in specimens occurring during cold seasons. The temperature of about 8 degrees C forms a boundary between warm and cold seasons. The author assumes that similarly as G. aphyae and G. macronychus also other members of the genus Gyrodactylus living in climatic zones with regular change of seasons will react similarly on the annual variation in the environmental temperatures.


Cestodes of ruminants in Afghanistan.

Cestodes of ruminants in Afghanistan. Five cestode species parasitizing ruminants were found for the first time in Afghanistan: Moniezia benedeni, M. expansa, Avitellina centripunctata, Stilesia globipunctata, and Thysaniezia giardi.


Morphological and histochemical demonstration of hooks in the rostellar region of Cysticercus bovis. Hooklets and early developmental stages of hooks were discovered in the tegument among the microtriches in the rostellar region of 83- and 108-day-old Cysticercus bovis. The cortical layer of hooks consists of proteins with tyrosine and SS groups. The rostellar sac and bulb are distinctly developed in the parenchyma of the rostellar region.


Contribution to the knowledge of synanthropic flies in the Mongolian People's Republic. A survey is given of 23 species of synathropic and synbovine Diptera collected in the years 1968, 1969 and 1972 in the Mongolian People's Republic by J. Minár. Besides the faunistical comments, the species of hygienic-epidemiological or public health importance are discussed.


First record of a cyclopoid host-Mesocyclops leuckarti (Claus) for an acanthocephalous worm-Acanthosentis dattai Podder from Delhi (India). Among seven species of Cyclops encountered in four water ponds kept under observation in Delhi during 1973-74 period, six specimens of Mesocyclops leuckarti (Claus, 1857) were found to harbour juvenile stages of Acanthosentis dattai Podder, 1938, parasite of the freshwater fish of the genus Barbus. This is the first record of members of Cyclopidae as intermediate hosts of Acanthocephala in India. The morphology of hitherto unknown juvenile stage of A. dattai is described in this note.


Rhabdochona minima sp. n. (Nematoda: Spiruroidea) from the loach, Noemacheilus inglisi (Hora), of Nepal. A new nematode species, Rhabdochona minima sp.n., is described from the intestine of Noemacheilus inglisi (HORA) OF Nepal (River Ganges drainage system). Characteristics features of this species (only males were found) are the small size of body, size and type of spicules, shape of tail and arrangement of caudal papillae. On the basis of its morphology, R. minima sp.n. belongs to the subgenus Globochona sensu Moravec, 1975. The species Rhabdochona cavasius Rehana et Bilqees, 1973 is considered to be a synonym of R. mazedi Prassad et Sahay, 1965.


The measurement of blood glucose and the definition of hypoglycemia. Hypoglycemia is a chemical definition and must be distinguished from neuroglycopenia which is a clinical one. Accurate measurement of blood glucose is possible but many methods still in use may yield incorrect and sometimes dangerously misleading results. Various definitions of hypoglycemia are discussed in relation to methodology and technique of blood glucose measurement. The distinction between fasting and reactive hypoglycemia is emphasized.


Hormonal counterregulation in ethanol-induced hypoglycemia-Glucagon and cortisol secretion in pigs. Plasma glucagon and cortisol levels were determined in pigs during ethanol-induced hypoglycemia. This hypoglycemia is due to an inhibition of gluconeogenesis which could be related to an abnormal secretion of gluconeogenetic hormones. In six pigs the infusion of ethanol for seven hours (6 mg/kg/min) induced a significant decrease of plasma glucose which was associated with a significant increase of plasma glucagon in the portal vein, femoral artery and hepatic vein. Corresponding with the period of maximal hypoglycemia, plasma cortisol in the femoral artery was also significantly increased. On the other hand, plasma insulin levels were consistently reduced during hypoglycemia. In a second group of six pigs ethanol was infused along with a glucose infusion (3 mg/kg/min) in order to obtain a relatively constant glucose concentration. In this group ethanol did not produce any significant modification of plasma glucagon and cortisol. Therefore, glucagon and cortisol hypersecretion is related to hypoglycemia induced by ethanol. Both the increase in plasma glucagon and cortisol and the decrease in plasma insulin could represent a protective mechanism against alcohol-hypoglycemia.


Hypoglycemia--real and imaginary.

Hypoglycemia--real and imaginary. Hypoglycemia, and especially esential reactive hypoglycemia, is overdiagnosed in some parts of the world possible because of misplaced zeal on the part of certain clinicians or misinterpretation of laboratory data relating to the prolonged oral glucose test. This hypoglycemia quackerly has given rise to much concern amongst medical scientists, some of whom have felt it necessary to issue a public warning about the danger of misusing the diagnostic label of hypoglycemia.


Studies on the hyperglycemic effect of diphenylhydantoin in normal golden hamsters. Injected intraperitoneally at a dose of 100 mg/kg body weight into normal hamsters, diphenylhydantoin (DPH) induces a marked increase in blood glucose accompanied by a significant decrease in plasma insulin and a significant increase in plasma glucagon. After administration of phentolamine (5 mg/kg), the hyperglycemic effects of DPH is markedly reduced but remains statistically significant, plasma insulin levels are unchanged and the DPH-induced rise in plasma glucagon is significantly inhibited. Propranolol pretreatment (5 mg/kg) does not affect the DPH-induced changes in blood glucose, plasma insulin and plasma glucagon. Previous administration of reserpine (5 mg/kg/day for two days) does not modify the hyperglycemic response to DPH. These data suggest that the hyperglycemic action of DPH results from both a direct inhibitory effect of this compound on insulin secretion by the beta-cells and a direct stimulatory effect on glucagon secretion by the alpha-cells.


The role of enteric hormones in glucose homeostasis. A brief review  is given of the large numbers of hormones in the pancreas and gut. The concept of the 'entero-insular' axis is discussed and a critical appraisal is given of the claims for various proposed insulinotropic gut hormones. Gastric-inhibitory polypeptide appears at the present time to occupy a leading role in the entero-insular axis. Glucagon-like substances and vasoactive intestinal peptide are of importance in glucose homeostasis by having direct effects on carbohydrate metabolism. The study of the release of gut hormones after food ingestion would indicate that pancreatic glucagon exerts control on glucose hemeostasis during food ingestion, whereas gastric-inhibitory polypeptide may regulate insulin secretion after eating.


Studies on the pathogenesis of reactive hypoglycemia: role of insulin and glucagon. Fifty-eight patients with biochemical reactive hypoglycemia (blood glucose 45 mg% or less after a 100 g OGTT) were tested, of whom 11 subjects were obese with normal glucose tolerance, 9 were obese with chemical diabetes, 9 had chemical diabetes without obesity, 6 had undergone gastrectomy, 7 had renal glycosuria and 16 were apparently isolated. An exaggerated insulin response to oral glucose was associated with reactive hypoglycemia in the post-gastrectomy syndrome, in normal-weight patients with chemical diabetes and 44% of the patients with the isolated syndrome. In contrast, plasma-insulin values cannot account for the reactive hypoglycemia observed in obese patients (with or without chemical diabetes), in subjects with renal glycosuira and in 56% of the patients with the isolated syndrome. A study of pancreatic-glucagon secretion in a group of twelve subjects with "isolated normoinsulinemic reactive hypoglycemia" failed to demonstrate any significant abnormality in the secretion of this hormone during oral glucose tolerance test or intravenous insulin tolerance test. As suggested by Permutt et al. (1973) biguanide therapy may be useful in the treatment of patients presenting severe and symptomatic reactive hypoglycemia which does not respond to classical dietary management.


Alcohol hypoglycemia: hormonal changes.

Alcohol hypoglycemia: hormonal changes. Changes in hormonal (insulin, glucagon, cortisol and growth hormone), glucose and FFA levels in blood were studied in four young, normal subjects during, and following, alcohol infusion after 12 hours' fasting. Similar studies were made during and after saline infusions in the same subjects after a comparable period of fasting. At the end of the infusions of alcohol or saline an arginine test was performed in order to compare insular and pituitary responses. The same investigations were performed in another three young, healthy subjects after 36 hours' fasting. A chronic alcoholic suffering from hypoglycemia was studied after a 12 hours' fast when he was first seen and again nine months after alcohol withdrawal. The results are in keeping with the hypothesis that alcohol has a priming effect on islet alpha and beta cells when there is no substrate defect. When glycogen stores are exhausted hypoglycemia ensues. An adrenergic reaction supervenes and consequently FFA, cortisol and glucagon rise to high levels. The growth-hormone response to an arginine stimulus was lower after alcohol than after saline in all subjects. In the chronic alcoholic patient the plasma growth-hormone response was initially very poor to all of the stimuli, but after nine months' alcohol withdrawal pituitary activity had returned to normal.


A day treatment program for severely disturbed young children. An Illinois mental health center operates a day treatment program for young children, who have severe emotional disturbances, often accompanied by profound functional retardation of neurological impairment or both. The primary therapists are child-development specialists; most of the treatment is provided in a classroom setting, through small groups. The author reports on a study of 67 young children who had been treated and discharged, including their psychiatric diagnoses and psychological status at intake and discharge, family characteristics, and treatment outcome an average of two years and seven months after discharge. At that time all but four of the children were living at home. Fifty-two of them attended public school, most in regular classes, and the rest were in therapeutic day schools.


Irrational determinants of the place of psychiatric treatment. Observations of 392 women admitted to a psychiatric hospital indicated that 24 were well suited to treatment in a day center and that 208 could feasibly be treated there. However, only 59, or 28 per cent of those for whom day care was feasible, were able to take advantage of that alternative. The others were excluded by financial limitations, refusal to accept the day center option, administrative delays, and inaccurate classification of treatment setting. The authors believe that underuse of the day center was due as much to doctors' inexperience, personal biases, and unfamiliarity with the facilities as it was to psychopathology and financial realities. They found that many clinicians were not aware of the factors that affect their decisions about the use of a partial hospitalization setting.


Family coping with the mentally ill: an unanticipated problem of deinstitutionalization. The author studied 125 families to determine the effect of the current movement toward returning mental patients to their homes. From interviews with and attitudinal tests of those families, he reports that they will generally care for the former patient in their home, often with little shame or embarrassment, and usually without rehospitalizing him. But the former patient's presence, especially when severe psychotic symptoms persist, often puts heavy emotional and social strains on the families. He warns that although families accept the physical presence of the patients, the accompanying social rejection could have serious consequences for the community mental health movement.


Community families: an alternative to psychiatric hospital intensive care. For the past four years Southwest Denver Community Mental Health Services, Inc., has had a system of alternative families who take one or two psychiatric patients who need intensive treatment into their homes; the clients' average stay is ten days. Thus far approximately 220 client placements have been effectively carried out in a network of five homes. Clients who receive psychotropic medication have its effects monitored by a staff psychiatrist, medical nurse coordinator, and nurse clinician. A study conducted by independent researchers over the initial two-year period indicates that the homes are more effective in certain respects than a psychiatric hospital in providing intensive care.


Computerized system analyzes epidemiological data. The computer is a valuable tool in helping to analyze epidemiological data that are collected through the infection surveillance system. The computerized system described has many significant advantages over the manual system of infection surveillance: quick assimilation, computation, and dissemination of the nosocomial infection summary report (within seven working days of the month's end); identification of infection problems and problem areas; and ability to retrieve data necessary for a complete establishment of a hypothesis regarding cause and effect implicated by an epidemiological investigation. Above all, timely and accurate infection data must be obtained in order for the reports to be beneficial in the decision-making process used by the infection control committee. Manual systems of month-to-month correlation of infection data are difficult and extremely time consuming for the surveillance person. Often the infection control committee cannot act intelligently and quickly because it is not knowledgeable of current trends occurring within the hospital. The computer has a number of limitations, and any computerized surveillance system should be approached with caution, especially during the developmental stages. The computer uses input data, follows instructions, and thus formulates output. If the computer is given either inadequate input data or inaccurately programmed instructions, the output will be erroneous. Therefore, a close working relationship should be established between the epidemiologist and the hospital's data processing department. The goals of the system must be clearly defined and understood by both areas. Once the system is established, the output is only as good as the data supplied by the epidemiologist. If this system is properly utilized, valuable information can be obtained that would have been difficult to obtain using a manual surveillance method.


A review of prescription pricing and a call for equitable payment. All of these systems are designed in order than a fair and equitable profit may be included for pharmaceutical services but this profit need not be excessive. For many years, the pharmacy has been considered a profit generator to offset the losses in other services departments. However, because of increased consumer awareness of prices and the close scrutiny of third party payers, including the federal government, this practice appears to be diminishing. With enactment of a comprehensive national health insurance, it is unlikely that the government will allow the type of cost accounting whereby one department generates profit to offset a deficit in other departments. Therefore, hospitals must develop a fair, equitable, and efficient pricing system. It is believed that the per diem charge system may be the most suitable for several reasons. First, it provides a mechanism for the charging of services not associated with the dispensing of pharmaceuticals. Second, this system appears to be more efficient because it eliminates the need to price individual prescriptions, which may result in an annual savings of $20 per bed as reported in one study. Third, the per diem mechanism promotes cost efficiency by focusing attention on the actual daily operating cost of providing pharmaceutical services. It is obvious that the general public is aware of the expense of health care, including pharmaceuticals. Hospital pharmacy has enjoyed a relative period of immunity from such public scrutiny  for many years. We must, therefore, make every effort to encourage a pricing system that is equitable to both the hospital and the patient. In viewing these four mechanisms of payment, it is believed that the per diem rate for pharmaceutical services can and will be utilized to a much greater extent. When one considers its advantages along with the imminence of some form of a national health insurance program, this system appears to be the reimbursement mechanism of the future.


Effects of active and passive immunization on Mycoplasma pulmonis-induced pneumonia in mice. Parenteral immunization of C3H mice with viable Mycoplasma pulmonis organisms protected them from pneumonia induced by intranasal inoculation of these organisms. Spleen cells obtained from immunized mice were ineffective in preventing syngeneic recipients from developint respiratory disease. In contrast, convalescent-phase serum enhanced the clearance of mycoplasmas from the respiratory tract of mice challenged with a small number of organisms. Further, although 'immune' serum had no detectable effect on the number of mycoplasmas in the respiratory tract of mice challenged with a large number of organisms, such animals did not develop pneumonia. Since the pneumonia appears to be the results of the host's immune response to the mycoplasma, it is suggested that the transferred 'immune' serum may act by suppressing the immune response so that mice develop less severe lung lesions. This suggestion is supported by the observation that the complement-fixing antibody response of passively immunized mice was suppressed.


The effect of Leishmania tropica on stimulation of lymphocytes with phytohaemagglutinin. Cell-mediated immune (CMI) responses are important in the immunity against leishmanial infections. However, infection persists in the presence of CMI for unknown reasons. Evidence is presented that L. tropica and its products are capable of inhibition of the stimulation of lymphocytes by PHA. This inhibition is dose dependent, and not dependent on competition for nutrients in the medium, nor on neutralization of PHA. The inhibition is observed on the lymphocytes of species susceptible to leishmanial infection, and not operative in resistant species. The mechanisms of the lymphocyte suppression are discussed.


Decline of passively acquired antibodies in young and adult rats. The rate of decline (half-life) of passively acquired antibodies was studied in young and adult rats. There was a wide variation in half-life when varying concentrations of diphtheria or tetanus antibody were administered by intraperitoneal injection; half-lives ranged from 1-2 to 12-0 days in both age groups. When different concentrations of diphtheria and tetanus antibody were administered together by the same route, significant differences in half-lives were demonstrated in individuals of each group. Each of the curves describing the relationship between initial antibody titre and half-life took the shape of a rectangular hyperbola; individuals with high initial titres had short half-lifes, whereas in animals with low initial titres antibody declined at a slower rate. The results are in agreement with those previously reported for the decline of maternally acquired antibodies in infants and young rats and for the catabolism of IgG.


Experience with the dynamic compression plate (DCP) in 418 recent fractures of the tibial shaft. A consecutive series of 435 fresh fractures of the tibial shaft was internally fixed by the new dynamic compression plate (ASIF-DCP). All but 2 cases could be reviewed personally within 1-2 years after operation, while 15 patients had died. The functional results and postoperative complications are reported separately for the 334 closed and 101 open fractures. In spite of a higher rate of complication in the open fractures, their functional results were about as good as in the closed cases. In our experience the new dynamic compression plate proved to be very satisfactory for internal fixation of fractures of the tibia.


Lactic dehydrogenase isoenzymes following head injury. Serial levels of lactic dehydrogenase (LDH) isoenzymes have been measured in 92 neurosurgical patients with damaged brains, including 77 suffering from head injury. Serum LDH isoenzymes 1 and 2 rise in the injured group and generally reflect the degree of parenchymal brain damage. The method has possible diagnostic applications, as well as some prognostic use.


The importance of the ulnar side of the wrist in fractures of the distal end of the radius. In a series of 81 fractures of the distal end of the radius, 20% had unsatisfactory results. Damage to the ulnar collateral mechanism adversely affects the clinical result despite a good anatomical result. Immobilization of injuries to the ulnar collateral mechanism should be in pronation and ulnar deviation even when there is no significant radial displacement.


Treatment of fracture-dislocation of the hip with complete destruction of the proximal end of femur by total hip arthroplasty. A case of fracture-dislocation of the hip with loss of bone from the proximal part of the femur due to a war injury is described. It is concluded that a total hip arthroplasty after 3 months is a suitable treatment.


The risk of deep-vein thrombosis after operations on a bloodless lower limb. A venographic study. In 17% of 40 patients undergoing operation in a bloodless field on the lower limb, thrombosis was diagnosed phlebographically. Phlebography was performed between the second and eighth postoperative day. The incidence of thrombosis in this series was relatively low, considering other reports on postoperative thrombosis and the theoretical dangers of thrombosis involved in the use of a tourniquet. Factors which could explain the relatively low frequency of postoperative thrombosis are discussed.


Non-union in fractures of the humeral shaft. Twenty-nine patients with non-union of the humeral shaft, who were treated in 3 major Vancouver hospitals, were studied. Reasons for non-union, effectiveness of various treatment methods, and complications are discussed. Fractures occurring in the middle third of the humeral shaft, comminuted or open fractures and those treated early by open reduction, are more prone to non-union. Nearly 50% of the patients with non-union were chronic alcoholics. Compression plating with cancellous bone grafting gave the best rate of healing. However, both early and late operative treatment gave a relatively high complication rate.


Medical planning for disaster in Israel. Evaluation of the military surgical experience in the October 1973 War, and implications for the organization of the civilian disaster services. During its 27 years of existence, Israel has experienced four wars and dozens of mass casualty situations from various causes. This experience has led to the development of a plan for the management of mass casualties. This plan was put to the test in the October War of 1973 and proved successful. Although disasters and procedures vary widely in time and location certain principles of organization and management apply to most of them. In this paper the organization of the evacuation and management of the casualties in the October War is evaluated and its implications in the organization of civilian disaster services discussed.


Hang gliding injuries. A preliminary report. Six cases of injury associated with hang gliding are reported. The history and technique of the sport are briefly described. Fractures of the spine and limbs are the commonest injuries encountered in this high risk activity and many of them could be avoided or reduced in severity by simple safety precautions.


Hepatic trauma involving the hepatic veins and vena cava. The control of massive haemorrhage in major hepatic injury with caval damage is extremely difficult. Our experience with 5 such patients is reported. The management and operative techniques involved are discussed. In 3 patients control was obtained and repair effected without recourse to internal caval shunting. One of these patients survived in spite of extensive injuries.


An unusual seat-belt injury in a doctor. The personal experience of a general practitioner who sustained a fracture-dislocation of the atlanto-axial joint is recorded. The inefficient application of an unyielding (non-inertial) lap and diagonal seat belt permitted this injury, although one does not know what other injuries might have occurred had the belt not been worn.


Interactions of antisera, sera, and oral fluid with glucosyltransferases. Partially purified glucosyltransferases (GTF) isolated from Streptococcus mutans OMZ 176 and respective rabbit antisera were used to study enzyme-antibody interactions. A comparison between sensitive serological techniques and a functional inhibition test based on a radioenzyme assay demonstrated that the latter test system was the only one that discriminated between different antisera. Positive reactions in high dilutions in the former test systems were explained by the involvement of non-GTF contaminants and/or antibodies against enzyme regions distant to the  catalytic site. The minute cross-reactions between two enzyme fractions and the respective antisera in the functional inhibition test indicated that the two immunogens contained mainly GTF that differed in the structure of their catalytic region. Control rabbit sera, rat oral fluid, and insoluble and soluble glucans considerably activated the GTF eluted with a 0.5 M phosphate buffer from hydroxapatite. It is suggested that these enzymes had additional binding sites for macromolecules inherent to rabbit sera and rat oral fluid, respectively, and that the observed increase in enzyme activity was due to a more stable enzyme conformation. Possibly the stimulation of GTF by the soluble glucan fraction was caused by a primer and/or acceptor function; however, this was not the case of the insoluble glucan. A stable complex was formed in the absence of the enzyme substrate, sucrose, the activity of which was not readily enhanced. It is concluded that the GTF of strain OMZ 176 are composed of multiple, multi-reactive molecules that enable these enzymes to act as cross-linking agents.


Production of highly cross-reactive hemagglutination-inhibiting influenza antibodies in ferrets. Ferrets were sequentially infected at time intervals of 3 weeks with different influenza virus A strains. It was found that secondary infection can result in the appearance of antibodies highly cross-reacting with a virus strain closely related to the strain of first infection. Such highly cross-reacting antibodies were designated as HCR antibodies. Evidence is presented that HCR antibodies were not antineuraminidase antibodies and, in addition, were not specifically oriented to the strain with which the crossing was observed. When using time intervals of 3 weeks between infections, no increase after secondary infection of antibodies oriented to the strain of first infection was recorded. However, when time intervals of 4 to 5 months between infections were used, secondary infections resulted in an increase of antibodies oriented to the strain of first infection ("original antigenic sin") but not in the appearance of HCR antibodies. In addition, antibodies combining specifically with both  infecting strains, designated as doubly specific antibodies, were found. Thus, the conclusion was reached that the original antigenic sin phenomenon and the appearance of HCR antibodies are mutually exclusive events.


Purification of complement-fixing antigens of Rickettsia sennetsu by ether treatment. Soluble and particulate complement-fixing antigens of Rickettsia sennetsu were prepared from spleen suspensions of mice infected with the rickettsia and treated with cyclophosphamide. The medium used during purification of antigens, a solution consisting of equal volumes of phosphate-glutamate-sucrose buffer and veronal-buffered saline, was suitable for obtaining antigens with high titers and no anti-complementary activity. By heat treatment, it was demonstrated that the soluble antigen was heat labile and the particulate antigen was heat stable. The soluble antigen was precipitated by 80% saturation with ammonium sulfate. Cross-complement fixation tests using both soluble and particulate antigens revealed that there was no antigenic difference among strains of R. Sennetsu. On the other hand, no cross-activity was observed between R. sennetsu and R. orientalis.


Role of Agrobacterium cell envelope lipopolysaccharide in infection site attachment. Lipopolysaccharide (LPS) isolated from Agrobacterium tumefaciens inhibited tumor induction by virulent bacteria. LPS from site-binding strains was not effective if added to the plant wound shortly after the bacteria, and LPS from avirulent, non-site-binding strains of Agrobacterium was not inhibitory regardless of the order of addition. However, LPS and whole cells of avirulent strains NT1 and IIBNV6, which lack of Agrobacterim virulence plasmid, were inhibitory. Chromosomal deoxyribonucleic acid thus determines specificity of this essential component of the Agrobacterium infection process.


Presence and subcellular localization of two distinct mitogenic fractions in the cells of Nocardia rubra and Nocardia opaca: preparation of soluble mitogenic peptidoglycan fractions. Fractionation of cells of Nocardia rubra and Nocardia opaca led to the separation of the cell wall and a "cytoplasmic" fraction. Both fractions were mitogenic for the splenocytes of AKR and nude mice and of rabbits. The peptidoglycan was the active part of the cell wall fraction. The products solubilized by the action of Streptomyces albus G peptidases on the peptidoglycan of N. rubra were mitogenic, but the products solubilized by lysoyme were not. Tentative structures are proposed for these fractions. The most active part of the cytoplasmic fractions could be sedimented by centrifugation and seemed to be related to the cytoplasmic membrane.


Demonstration of macrophage chemotactic factors in the aqueous humor during experimental immunogenic uveitis in rabbits. Factors in the queous humor capable of increasing the random migration and chemotaxis of monocytes were demonstrated during experimental uveitis in the rabbit. Injection of endotoxin-free human serum albumin into the vitreous produced a severe inflammation detectable after 7 days and maximal between 12 to 21 days. Aqueous humor was measured for chemotactic activity with a modified Boyden chamber, which permitted the use of volumes of less than 0.025 ml. Chematactic activity was measurable during the primary inflammation and remained elevated for a short period of time after clinical inflammation and anterior chamber cellular reaction had decreased. A severe reinduction uveitis could be initiated by the intravenous injection of human serum albumin after day 30. Chemotactic factors could be measured at high titers by 8 h after this intravenous challenge.


Complement system in pneumococcal infections. The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection.


Relationship of the cell wall composition of group H streptococci and Streptococcus sanguis to their serological properties. Previous studies indicated the a antigen was widely distributed among strains of Streptococcus sanguis and the group H streptococci. The cell walls of strains containing this antigen had moderate to large quantities of rhamnose, small amounts of phosphorus, and little to no ribitol. The molar ratios of the peptidoglycan amino acids and hexosamines suggested a di-alanyl cross bridge. The homogeneity of the walls of these strains suggested that serological group H can be considered synonymous with S. sanguis. In contrast those strains that did not contain the a antigen had only small amounts of rhamnose in their cell walls, galactosamine and ribitol were always detected, and large quantitites of phosphorus were present. The molar ratios of peptidoglycan components in the latter strains suggested a direct alanyl-lysl cross bridge. Although many of these strains had been classified either as S. sanguis or group H streptococci because of minor serological cross-reactions and similar biochemical properties, the distinct differences between the composition of their cell walls and those of S. sanguis and group H streptococci indicate that they do not belong in this species or group. The cell walls of strains containing the a antigen are relatively homogeneous and therefore it is suggested that cells containing this antigen be considered Lancefield serological group H.


Ontogeny of human cell-mediated immunity: age-related variation of in vitro infantile lymphocyte transformation. Thymidine uptake of unstimulated and of phytohemagglutinin (PHA)-, streptokinase-streptodornase (SK-SD)- and candida extract (candida)-stimulated lymphocytes of normal infants less than 20 months old was evaluated. Thymidine uptake of unstimulated and PHA-stimulated young infants' lymphocytes was avid, resembling that of newborn cells. Over periods of weeks to months, infantile lymphocytes demonstrated transition in unstimulated and PHA-induced thymidine uptake from response patterns like cord blood cells to ones more characteristic of adult lymphocytes. Candida- and SK-SD-induced thymidine uptake of lymphocytes from very young infants was likewise apparently quite avid, resembling cord blood cells. However, factoring out high unstimulated thymidine uptake by conversion of data to stimulation indexes clarified differing paces of acquisition of transformation responsiveness of the two naturally acquired infectious antigens. Specific lymphocytes reactivity to SK-SD was quite low in all groups of infants compared with candida-induced transformation, which in some infants acquired adult proportions.


Dextran-mediated interbacterial aggregation between dextran-synthesizing streptococci and Actinomyces viscosus. Streptococcus sanguis and Streptococcus mutans bind to the surface of Actinomyces viscosus, producing large microbial aggregates. Aggregates form rapidly and are not easily dissociated by vigorous mixing. The binding is mediated by dextran. Glucose-grown streptococci will not aggregate unless they are first mixed with high-molecular-weight dextran. Aggregation is induced with dextrans isolated from Leuconostoc, S. sanguis, or S. mutans. Sucrose-grown streptococci will adhere to A. viscosus without the addition of an exogenous source of dextran. A. viscosus will bind dextran and then bind glucose-grown streptococci. Aggregation occurs over a wide pH range and is dependent on cations. The aggregating activity of A. viscosus is both protease and heat sensitive. The aggregating activity of S. sanguis is heat stable but sensitive to dextranase.


Establishment of cutaneous Leishmania enriettii infection in hamsters. A model of a self-healing type of cutaneous leishmaniasis was established in hamsters using the guinea pig parasite Leishmania enriettii. L. enriettii was passaged several times in hamsters without losing its infectivity for guinea pigs or for hamsters. The course of the infection in hamsters resembled that of guinea pigs, with the exception that the lesion at the site of parasite inoculation did not ulcerate and no metastatic lesions developed spontaneously. Moreover, unlike guinea pigs, infected or recovered hamsters were skin test unresponsive to various preparations of L. enriettii antigens. However, histological examination of draining lymph nodes showed features of a cell-mediated immune response, and in vitro inhibition of macrophage migration was demonstrable using peritoneal exudate cells from recovered animals and specific leishmanial antigen. Antibody was demonstrable by indirect immunofluorescence starting 1 week after infection. Recovered animals were immune to reinfection; however, the passive transfer of peritoneal exudate cells or serum from recovered animals did not confer protection against L. enriettii infection in normal animals.


Interferon preparations enhance phagocytosis in vivo. Previous studies have shown that interferon (IF) preparations enhance phagocytic activity in cultured mouse peritoneal macrophages. It is shown here that cell culture fluids containing large amounts of IF, which had been treated with acid and clarified of the inducer, Newcastle disease virus, enhanced phagocytic activity when injected into mice. Enhanced phagocytic activity also was observed after injection of Newcastle disease virus into mice, but the contribution of IF to this event was unclear. The kinetics of the phagocytic response to inducers in vivo were biphasic. Depression of phagocytosis occurred around 16 to 18 h after injection of Newcastle disease virus. The observed enhancement began about 12 h later and lasted for at least 60 h more. It was concluded that the complexity of the response of mice to an inducer makes analysis of the role of IF in the ensuing events difficult. However, because of documented phagocytosis-enhancing effects of IF in vitro, it is very likely that the in vivo effects observed here are to some degree mediated by IF. On this basis, the concept of the activity of IF as a lymphokine is potentially expanded.


Presence of pili in species of human and animal parasites and pathogens of the genuscorynebacterium. The presence of pili in human and animal parasites and pathogens of the genus Corynebacterium was examined. C. kutscheri, C. diphtheriae, and C. pseudodiphtheriticum possessed a fairly large number of pili, ranging from dozens to more than a hundred, in 91 to 100% of the bacterial cells. C. equi, C. hoagii, C. xerosis, C. pyogenes, and C. murisepticum had only a small number of pili in 10 to 37% of the bacterial cells. In C. bovis, C. striatum, and C. pseudotuberculosis, pili were detected in only 0.5% to 3% of the bacterial cells. The pili were similar to each other and to those of C. renale; they were not rigid and had a tendency to form bundles. The length of pili usually ranged from 0.2 to 3 mum, and their diameter was within a 2- to 6-nm range.


Ampicillin polymers as elicitors of passive cutaneous anaphylaxis. The ability of ampicillin polymers to elicit passive cutaneous anaphylaxis (PCA) reactions in guinea pigs was analyzed. Mediating antibodies were raised in rabbits against a crude preparation of 6-aminopenicillanic acid (6-APA). It was found that large ampicillin polymers were potent elicitors, 1,000-fold better than benzylpenicillin polymers. Small polymers in high concentrations did not elicit PCA reactions but inhibited the activity of the larger polymers. This inhibition was more pronounced that that of ampicillin monomer. High molecular weight of ampicillin polymer in the amount of 0.1% in an ampicillin solution manifested its PCA activity. The tendency of ampicillin to polymerize, particularly when kept in solution, makes this observation worth considering. The PCA reactions described were penicilloyl-specific as verified by immunosorbent experiments.


Effect of season of immunization of the induction of delayed contact sensitivity in the guinea pig. The degree of delayed contact sensitivity induced in guinea pigs was greater when sensitization was attempted in winter than when attempted in spring and summer.


Allergen extract of horse hair and dandruff. Quantitative immunoelectrophoretic characterization of the antigens. Freeze-dried extract of horse hair and dandruff was obtained by extraction, centrifugation, dialysis and freeze-drying. Quantitative immunoelectrophoresis using rabbit antibodies revealed the extract to be composed of 25 antigens of which some were mutually partial identical; 4 were serum-specific and non showed partial identity to solubilized hair proteins. Partial identity to antigens to serum and extract from hair and dandruff of cow, dog, cat, guinea pig, and of extract from house duct was demonstrated. After subjecting the extract to dialysis, ultrafiltration, freeze-drying and storage below 37degreesC for not more than 24 h the antigenic stability and the allergenic activity were unaffected. The effect of enzymatic degradation of the individual proteins with regard to antigenic stability and allergenic activity was also examined.


Identification of allergens in extract of horse hair and dandruff by means of crossed radioimmunoelectrophoresis. Sera from 26 patients and 4 normals were examined for specific IgE binding to antigens of extract of horse hair and dandruff by means of CRIE. 22 of the patients were RAST- and intracutaneous-positive to horse extract. 4 more of the patients were RAST-negative to horse allergens, but showed allergies to extract of allergens from sources other than horse. The remaining four sera from controls were RAST-negative to horse and had no history of allergy. Antigens of horse hair and dandruff showed a significantly higher degree of binding to specific IgE in the sera from the first group of patients than was the case for the two other groups. A linear correlation between specific IgE binding in RAST and in CRIE was found for the first group of patients. On the basis of these results the major allergens of the examined extract of horse hair and dandruff were identified.


Isolation and partial characterization of three major allergens of horse hair and dandruff. Three major allergens of horse hair and dandruff have been isolated. The fractionation procedures involved various combinations, described in detail, of ethanol precipitation below --5degreesC, cation- and anion-exchange chromatography, and gel filtration. UV absorption, quantitative immunoelectrophoresis and RAST inhibition were used to monitor the separations. Protein impurities constituted less than 5% in all cases. The molecular weights of the isolated proteins were 1.9 X 10(4), 5.1 X 10(4) and 3.1 X 10(4) daltons, respectively. The pIs were determined as 4.1, 3.8 and 3.9, respectively. The amino acid analysis of the isolated allergens revealed large variations in their amino acid composition which might explain different reactivities in RAST experiments. The allergenic activities of the isolated antigens were determined by RAST inhibition and prick tests.


A solid-phase radioassay for the detection of anti-thyroglobulin antibodies in different immunoglobulin classes. A convenient technique suitable for the routine estimation of IgG and IgA anti-thyroglobulin antibodies has been devised. The assay involves the binding of anti-thyroglobulin to human thyroglobulin linked to the surface of plastic tubes; the amount of antibody bound is then determined by adding radiolabelled anti-human IgG or IgA. IgG antibody was raised in virtually all patients and significantly elevated levels of IgA antibody were also found in some patients. The test should prove helpful in diagnosis and provide quantitative evaluation of research studies.


Role of sensitized cells in antitubular basement membrane interstitial nephritis. The pathogenic effect of antitubular basement membrane (TBM) antibodies in anti-TBM interstitial nephritis has been demonstrated. To determine the relative role of sensitized cells in inducing this lesion, lymph node cells (LNC) alone or a combination of LNC and peritoneal exudate cells were transferred from Brown Norway (BN) rats, previously immunized with TBM into unimmunized BN-recipient rats. Cells were transferred directly under the recipients' renal capsules. Although significant tubular lesions were induced by the cells, the lesions were usually mild and always focal. Hence, sensitized cells do not appear to be central to the pathogenesis of anti-TBM nephritis.


Inflammation-inducing factors from human lymphocytes. Correlation with polymorphonuclear leucocyte migration enhancement of inhibition. Factors capable of inducing inflammatory reactions in the skin of normal guinea pigs have been demonstrated in culture supernatants from PPD-stimulated human mononuclear cells from tuberculin-positive donors. The reaction is characterised by erythema, induration and infiltration with mononuclear cells and some polymorphonuclear leucocytes. These supernatants either enhance or do not affect polymorph migration in the leucocyte migration test. Supernatants that inhibit migration in vitro produce a marked polymorph infiltration upon intradermal injection.


Adjuvant effect of lysolecithin analogues on the development of contact sensitivity in mice. The influence of two lysolecithin analogues on the development of contact sensitivity (CS) to picryl chloride in mice was studied. Both substances were shown to have an adjuvant effect on the primary CS response, but depending on dosage of adjuvant and antigen, the timing of adjuvant injection, and the strain of mice employed, the relative activities of the two substances varied considerably. Large amounts of one of the adjuvants were less stimulatory than small amounts. Both substances had a suppressive effect on the development of CS following repeated administration of picryl chloride. The results are discussed in relation to hypotheses on the cellular targets for, and mode of action of, immunological adjuvants.


Modulation of the immune response by passive antibodies. II. Effects of passive anti-hapten and anti-carrier antibodies on the immune response to a sustained antigenic stimulation. The present work is an attempt at understanding the modulating effects of passive antibodies on the immune response to a sustained antigenic stimulation. Passive anti-carrier and anti-hapten antibodies were injected 24 h before immunization with the hapten carrier conjugate into guinea pigs subsequently injected intradermally with the carrier alone on days 11 and 23. The results showed that passive anti-carrier antibodies blocked the effects of intradermal injections of carrier, i.e., desensitization and increase of antibody synthesis to the carrier. Passive anti-hapten antibodies did not prevent desensitization and delayed antibody synthesis to the carrier. The mechanisms whereby passive antibodies modulate the response to a sustained antigenic stimulation are discussed.


Binding of morphine by serum globulins from morphine-treated rabbits. I. Induction and measurement of binding. Treatment of rabbits with morphine under conditions defined in this report leads to significant and reproducible increases in the binding of morphine by serum globulins. Complexes formed are readily dissociable so that the conditions employed in measuring binding become critical. The data presented document the effects of several variables upon the results of binding measurements. Also described are treatments that lead either to "priming" or to the inhibition of a subsequent response.


Heterogeneity of rabbit homologous skin sensitizing antibodies: IgE and a new subclass IgGa. Homologous skin sensitizing antibodies in the rabbit can be differentiated by their requirement for complement in expressing the passive cutaneous anaphylactic reaction as complement dependent (CD) or complement independent (CI). CI antibodies are representative of the IgE class, while the CD antibodies belong to a proposed new subclass of IgG designated IgGa (a = anaphylaxis). The following are characteristics of CI (IgE) antibodies: elution at 0.05 M on DEAE at pH 8.1 migration ahead of 7S in ultracentrifugation, molecular weight 215,000 daltons by Sephadex G-200, fast gamma-electrophoretic mobility, isoelectric point, pI = 4.98 (5.68-4.58), 85-95% heat sensitivity, sensitivity to reduction plus alkylation and option at 0.01 M on DEAE, 7S in ultracentrifugation, MW 138,000 daltons, slow gamma-electrophoretic mobility pI = 6.90 (8.30-5.70), resistance to heating and to reduction plus alkylation and 1-day optimal SP. CI antibodies could be absorbed by anti-Fab, anti-epsilon, the homologous antigen and were not absorbed by anti-gamma, anti-alpha, or heterologous antigens. The CD antibodies were absorbed by anti-Fab, anti-gamma and not absorbed by anti-epsilon, anti-alpha, or heterologous antigens.


Receptors for antibody-opsonic adherence on the eosinophils of guinea pigs. Eosinophils have recently been implicated in antibody-dependent cell-mediated damage to schistosomula. Because of this, eosinophils of the guinea pig have been examined for surface receptors capable of giving antibody opsonic adherence; a rosetting reaction has been used. The eosinophils were shown to possess Fc receptors for homologous immunoglobulin. No selective difference between IgG1 and IgG2 was observed. In marked contrast to macrophages, guinea pig eosinophils failed to show opsonic adherence to red cells sensitized to a comparable degree with rabbit antibody. With red cell antibodies made in the pig, however, the reciprocal situation held, namely opsonic adherence was stronger with eosinophils than with macrophages.


In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease. In vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A- and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA.


Imitation in the family: a study of older parents and their adult sons. Older parents and their adult sons (fifteen father-mother-son triads) participated in this study which investigated whether imitative behavior is prominent in these families and whether interpersonal perceptions are related to the degree of imitation. Both perceptual and moral imitation tasks were used and personality descriptions were obtained on dimensions of activity, potency, and evaluation. Adult sons were found to imitate their parents on both tasks and particularly their fathers on moral issues. Older parents also were found to imitate their sons in a possible "reversal" of the direction of identification. Differential patterns of interpersonal perceptions were related to imitation for the three groups. Potential theoretical explanations are discussed.


The ecology of adaptation to a new environment. The intrainstitutional room transfer of 48 elderly residents was studied by direct behavior-mapping techniques. Data were obtained on the physical location, body position, and behavior of both residents and staff on a large number of tours of residential floors preceding and following the move. About half of the hypotheses suggesting that greater passivity and restriction in social space would occur following the move were supported. These responses were seen as adaptive in allowing the individual to comprehend the new environment prior to moving out more actively.


The impact of housing relocation on the elderly: an alternative methodological approach. This article examines the impact of housing relocation on the patterns of interaction and life satisfaction of a sample of older, married adults living in an urban area of central Arkansas. Interviews were conducted with 115 individuals residing in congregate housing and with a matched sample of 105 persons living in independent residential units. Respondents in the two settings fail to demonstrate significant differences in frequencies of social interaction. Patterns of interaction in five specific areas also reveal no appreciable variation. In addition, the time-related effects of congregate dwelling are suggestive but not confirming of negative changes in both interaction and satisfaction. On the other hand, regardless of residential duration, health, sex or age, independent residents exhibit higher life satisfaction. The data suggest the congregate setting to possess insufficient resources to offset the objective and subjective decrements of old age.


The health status and the health care problems of the aged in an Italian community. This study had the purpose of identifying the health needs of the elderly population of a small urban Italian community for the purpose of planning sociomedical services. The data were collected by interviewing a stratified random sample of 1291 individuals over sixty years of age. About one third sample reported poor health. However, health complaints, both physical and mental, were particularly common among the persons living in disadvantaged social and economic conditions. The great majority of the respondents were found to be self-sufficient, and ambulatory. The results indicate that the present health needs of the elderly living in the community require new health services, such as home care, which will permit the elderly to avoid future hospitalization.


Age, anxiety, and self-reported health.

Age, anxiety, and self-reported health. A sample of 472 normal males ranging in age from twenty-five to eighty-two was divided into anxious and adjusted groups on the basis of a cluster analysis of the Cattell 16PF test, and compared for scores on a self-report measure of health. While the anxious men reported more symptoms than the adjusted in the young and middle age groups, there was no difference in the old group. Although anxiety was found to be unrelated to health as evaluated by physicians' examinations, the anxious men indeed reported more health problems in eight major areas of health concern than was warranted by their actual physical health status. This relation also did not hold in the old group. Anxious men seemed to be more vagilant about their health in young and middle age groups, but not in the old group. This was interpreted as a defensive denial of symptoms in the old anxious group; for a person with trait anxiety, anxiety about approaching death and increasing health problems is just too much to bear, and he resorts to denying symptoms in an effort to diminish his anxiety.


". . . Change and sameness . . ." reconsidered. This paper acknowledges and responds to Jack Block's statistical critique of the author's previously reported study of changes and sameness in personality development. The critique was apt, and calls attention to the difficulty of working appropriately with numerous, multiply-assessed variables. A re-analysis of the data is presented here. The general pattern of findings remains consistent with the original interpretations, but the re-analysis produced some differences as well.


Resistance to isolation among elderly widows. The widow's ability to resist isolation in old age-to either maintain the involvement of earlier years or develop new social networks-may be conditioned by a number of different factors. Drawing upon a survey of 409 widows, age sixty-five and older, from the Piedmont region of South Carolina, this study concludes that good health and the availability of economic resources are the primary factors which facilitate involvement with family, neighbors and friends, and participation in a number and variety of daily activities. In addition, those widows who were more educated participated in more activities; those living in small towns and rural areas were more involved with family and friends; and white widows saw more of their children, while black respondents were more active and knew more of their neighbors. Finally, the availability and degree of contact with children was unrelated to other activities, while friendship and neighboring was positively associated with taking walks, shopping, and attendance at religious services and other organizational meetings.


The increase in working years due to elimination of cancer as a cause of death. The relative significance of various forms of cancer in terms of causing death is analysed by estimation of the increase in person-years of working age (20-64 years) following elimination of the disease. Methods based upon the theory of competing risks are applied to the statistics on causes of death in Finland during the years 1966-70. It is estimated that if there were no lung cancer (the commonest type of cancer in both morbidity and mortality statistics in males in Finland) the annual deaths saved would yield 5,900 working years (both sexes combined). Leukaemia and cancer of the stomach would be next in rank order, with figures of respectively 4,000 and 3,900 working years more. Female cancer with the highest incidence, that of the breast, would be characterized by 2,900 additional working years. The significance of types of cancer that affect young people is stressed in these calculations: leukaemia, brain tumours and lymphomas (both sexes combined) are 6th, 12th and 11th respectively in the statistics of cancer causes of death, but 2nd, 4th and 6th respectively in the list of additional working years to be gained by elimination of the disease. On the other hand, cancer of the prostate, 3rd in males according to the annual numbers of cancer deaths, would take the 15th position for the increase in working years in males. If no risk of cancer existed, the annual deaths saved would produce 36,000 working years, a figure exceeded only by those for cardiovascular diseases (55,000 working years) and accidents (51,000 working years). The results indicate that no practical differences exist between the results derived under the assumptions of various models for competing risks, but that the exclusion of competing risks may result in considerable degrees of bias in estimation if the population has a high general mortality.


Concanavalin A receptors on the surface membrane of lymphocytes from patients with African Burkitt's lymphoma and lymphoma cell lines. Lymphocytes isolated from the peripheral blood and from tumor tissues of patients with African Burkitt's lymphoma have been studied for cap formation and agglutinability by Concanavalin A (Con A). Peripheral blood from healthy adult persons served as a normal control and blood from patients with carcinoma served as a non-lymphoma control. These studies included 29 patients with Burkitt's lymphoma, 93 with carcinoma, and 105 healthy adult persons, as well as tumor tissues from 13 patients with Burkitt's lymphoma. The great majority of the carcinomas were from the face and neck regions. Lymphocytes from the blood of the majority of patients with Burkitt's lymphoma, as well as those from tumor tissues, exhibited a reduced cap-forming ability (2-6%) and increased Con-A-induced agglutinability compared to lymphocytes from healthy normal donors and from patients with carcinoma, although some of the lymphocytes from patients with carcinoma had a somewhat lower range of cap formation than the lymphocytes from healthy donors. No difference was observed in the interaction with Con A of lymphocytes from the different types of carcinoma studied. Eight lymphoid cell lines were established in our laboratory from the tumor tissues of patients with Burkitt's lymphoma. The cap-forming ability and agglutinability by Con A of these lines was examined and compared to those of the "classical" lymphoma lines: Raji, Daudi and P3HR1. All cell lines exhibited an increased Con-A-induced agglutinability and a reduced cap-forming ability compared to normal lymphocytes, except for P3HR1 cells which exhibited a cap-forming ability of 15-20%. These findings are discussed in relation to the association of the lymphocytes with malignancy and as a possible aid in the differential diagnosis between malignant lymphomas and other diseases.


Relapse in Burkitt's lymphoma.

Relapse in Burkitt's lymphoma. Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty-five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p less than 0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration less than 12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration greater than 12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed.


Experimental studies on betel nut and tobacco carcinogenicity. Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis.


Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats. An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p less than 0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment.


Ainhum: treatment with intralesional steroids. Ainhum is a rare constricting band disease, usually affecting digits and resulting in spontaneous amputation. Prompt symptomatic relief and latter partial resolution of the fibrotic band followed intralesional steroid injection in the case presented.


Deep mycoses prevalent in the Igbos of Nigeria. During a 3-year period, 6 cases of Africal histoplasmosis, 6 of phycomycosis and 5 of mycetoma were recognized histologically in 0.4 per cent of 4,307 surgical specimens removed from Nigerian Igbos and examined at a central laboratory. Undoubtedly, these cases are but the representatives of the mycological iceberg existing in this part of the world. Our experience suggests that collaboration between physicians, pathologists and mycologists should bring about increased international awareness of the deep mycoses.


Straight-hair nevus syndrome: a case report with scanning electron microscopic findings of hair morphology. Straight-hair nevus of the scalp is a distinct clinical entity. A case is reported and 2 other cases from the literature are reviewed. In our patient, specific morphology of the hair shown by scanning electron microscopy suggested a disorder in keratogenesis from loss of cuticular cells. Straight-hair nevus is probably a form of localized trichodysplasia.


Thermodynamic parameters of transfer of N-acetyl ethyl esters of different amino acids from organic solvents to water. The distribution coefficients of N-acetyl ethyl esters of glycine, diglycine, beta-alanine, alanine, valine, norvaline, leucine and norleucine between water and different organic solvents have been measured at different temperatures. Similar distribution coefficients have been measured for simple amides, urea, formamide, acetamide and N-methyl acetamide. From the distribution measurements, deltaGtr, the free energy of transfer of the solutes from organic solvents to water has been calculated. The temperature dependence of the distribution coefficient values has been utilised to determine the enthalpy of transfer, deltaHtr, and entropy of transfer deltaStr for the above process. From these results similar thermodynamic parameters for the transfer of different nonpolar side chains and peptide groups have been determined and compared with the available data in the literature.


Cleavage of human serum transferrin with N-bromosuccinimide. Human serum transferrin was fragmented by N-bromosuccinimide and reduction-alkylation. It was observed that there were at least two each of tryptophanyl-serine and tryptophanyl-aspartic acid, and one each of tryptophanyl-alanine and tryptophanyl-glutamic acid bonds. The size of fragments detected by polyacrylamide gel electrophoresis ranged from 8,000 to 70,000 daltons. Several of the fragments were isolated in a homogeneous form with respect to molecular weight, but were shown to be mixtures of at least five molecular species each by end group analysis.


The primary structure of muskrat pancreatic ribonuclease. Pancreatic ribonuclease from muskrat (Ondatra zibethica) was isolated and its amino acid sequence was determined from tryptic digests of the performic acid-oxidized and the reduced and aminoethylated enzyme. The peptides have been positioned in the sequence by homology with other ribonucleases. This could be done unambiguously for all peptides except Arg-Arg (tentative position 32-33) and Ser-Arg (tentative position 75-76). The amino acid sequences of the peptides were determined by the dansyl-Edman method, with the exception of residues 23-25 and 99-102, which were positioned by homology. The enzyme differs in 38 positions from the enzyme from rat and in 31-42 positions from other mammalian pancreatic ribonucleases, while rat ribonuclease differs at 44-52 positions from the other enzymes. These data point to a common ancestry of the enzymes from muskrat and rat and an increased evolution rate of rat ribonuclease after divergence of the ancestors of both species. Muskrat ribonuclease contains no carbohydrate, although the enzyme possesses a recognition site for carbohydrate attachment in the sequence Asn-Val-Thr (62-64).


Proton magnetic relaxation dispersion in human fluoromethaemoglobin solutions. The solvent proton spin-lattice relaxation time of high spin Fe3+ (S=5/2) human A fluoromethaemoglobin aqueous solutions was measured at 14 Larmor frequencies in the range from 2.2 to 96 MHz. The observed paramagnetic relaxation rates are analysed in terms of the Solomon-Bloembergen theory, with the g-tensor value of 2 based on the consideration of the protein tertiary structure. From the H2O (pH 6) haemoprotein solution relaxation data, tau(c)  =(9.3+/-0.3) X 10(-10) sec. If the total relaxation rates are corrected for the "outer-sphere" paramagnetic contribution, tau(c)=(6.5+/-0.4) X 10(-10) sec. The latter correction is obtained from the p.m.r. of the non-exchangeable aliphatic protons of C2H4(OD)2 added to the D2O-solution of fluoromethaemoglobin. Assuming that single proton transfer is taking place through the protein channel along the axis normal to the haem (g=2), the protein "binding" site is at a distance of 3.93 to 3.98 A from the haem Fe3+ ion.


Silver-enhanced radial immunodiffusion assay of plasma apolipoproteins. Silver-staining of immunoprecipitates extends the sensitivity of the radial immunodiffusion assay by tenfold. This modification permits the quantification of apolipoproteins A-I, A-II, C, and E at levels of 0.2-1.0 mg/dl in plasma samples at a sensitivity threshold of 10 ng. The silver-enhanced radial immunodiffusion method is readily adapted from the standard method, simple and inexpensive to perform, and does not require costly instrumentation. These advantages make the modified RID assay an attractive alternative to other forms of immunoassay.


Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction. We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.


Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies. The objective of this study was to investigate how a conformational change in lipoprotein lipase (LPL) affects its molecular functions. Monoclonal antibodies (MAbs) were raised against purified bovine milk lipoprotein lipase. MAb 5D2 bound to human and bovine LPL both before and after denaturation of LPL. MAb 5F9 also recognized LPL from both species, but only after denaturation of the antigen, suggesting that a conformational change led to exposure of a previously hidden epitope. The MAbs were used in two sandwich enzyme-linked immunosorbent assays (ELISAs). One ELISA used the same MAb (5D2) to coat the plate and detect the bound antigen. This ELISA thus required the same epitope to be present in duplicate for detection (as would be the case with a dimeric antigen). The second ELISA used MAb 5F9 to coat the plate and MAb 5D2 to detect the antigen. This ELISA detected LPL only after it had been denatured. By measuring the same sample before and after denaturation with guanidine hydrochloride (GuHCl) in the 5F9 ELISA, and subtracting one from the other, a measure of native LPL was obtained. In inactivation experiments using human LPL, activity and the measure of LPL mass obtained in the 5D2 ELISA decreased and were related inversely to the measured mass obtained in the 5F9 ELISA which increased, indicating that loss of activity is closely linked to dimer dissociation and loss of native conformation. The effect of conformation and dimeric structure on LPL-heparin interaction was studied by heparin-Sepharose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)


The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery. Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery.


Comparison of specific immunoassays for detection of the beta-core human chorionic gonadotrophin fragment in body fluids. We have validated two new methods, one radioimmunoassay (RIA) and one immunoradiometric assay (IRMA), for the detection of beta-core hCG fragment (beta C-hCG) in body fluids. In addition, we have compared their performance with two other assays designed for beta C-hCG quantification. The RIA uses a rabbit polyclonal antibody raised against pure beta C-hCG which has a high affinity constant, is sensitive to 5 pmol/l, and has significant cross-reaction only with the free beta LH subunit. The IRMA, designed in a liquid phase, uses the same polyclonal antibody associated with a 125I-labelled mouse monoclonal antibody (32H2) raised against beta hCG, is sensitive to 1.5 pmol/l, and does not cross-react significantly with any related glycoprotein. Comparison between these two assays and two others previously published was made by measuring beta C-hCG in urine from healthy pregnant women (n = 47) and gave correlation coefficients higher than r = 0.960 with any combination. Analysis of beta C-hCG in urine of non-pregnant subjects (n = 238) showed measurable beta C-hCG in 8.8% (levels ranged from 5 to 34 pmol/l) with the IRMA and 88.3% with the RIA (n = 30; ranging from 28.4 to 228 pmol/l) (P = 0.05). We concluded that, despite different affinities of the antibody involved and different cross-reactivities with related glycoproteins, the four assays we examined may be equally employed to detect beta C-hCG in pregnancy urine. However, the IRMA appears to be more appropriate for beta C-hCG analysis in non-pregnant individuals, specifically in postmenopausal women because of the high cross-reactivity of the RIA with free beta LH or beta fragments of other glycoproteins. These studies have significance for our understanding of the physiology of beta C-hCG in cancer, pregnancy and after the menopause.


Distribution of the beta-core human chorionic gonadotrophin fragment in human body fluids. The origins of a fragment of the human chorionic gonadotrophin (hCG) molecule, beta-core (beta C-hCG) were studied by analysis of beta C-hCG concentrations in biological fluids. In addition, the ability of the placenta to produce the fragment and the metabolism of hCG to beta C-hCG by human granulosa cells was determined in tissue culture. Finally the conversion of exogenous hCG to beta C-hCG was studied in vivo. The fragment was present in pregnancy urine as well as that from premenopausal and postmenopausal subjects. The highest concentrations were found in pregnant women. Ratios of beta C-hCG to intact hCG were higher in pregnancy urine when radioimmunoassay (RIA) was used compared with immunoradiometric assay (IRMA) (0.67 and 0.37 respectively). Concentrations of beta C-hCG were higher in postmenopausal urine than in premenopausal specimens. A significant amount of a high molecular weight beta C-hCG immunoreactive material was found in serum samples after size separation, and the molar ratio of beta C-hCG/hCG was estimated as 0.019. Amniotic fluid also contained small quantities of two forms of immunoreactive beta C-hCG and the ratio of 0.01 for authentic beta C-hCG/hCG increased to 0.026 when the high molecular weight form was considered. Cultured trophoblastic tissue released material with beta C-hCG immunoreactivity in the medium and chromatographic separation revealed that the majority of this material was of higher molecular weight compared with the authentic beta C-hCG form. beta C-hCG was the principal glycoprotein found in follicular fluid after hyperstimulated folliculogenesis and intramuscular injection of 5000 IU hCG. We also demonstrated that 26% of follicular fluid samples (n = 50) were positive for beta C-hCG; levels ranged from 5.2 to 23.0 pmol/l (13.1 +/- 5.7); S.D.) when a specific IRMA was used. The RIA could detect beta C-hCG in 48 samples (96%), levels ranging from 7.0 to 28.5 pmol/l (19.4 +/- 5.2). Moreover, granulosa cells cultured in the presence of hCG were able to degrade the intact molecule to both high molecular weight and authentic immunoreactive forms of beta C-hCG. After gel filtration, material of molecular weight over a wide range and immunoreactive for beta C-hCG was present in human seminal plasma. Assaying 74 samples of this fluid by IRMA, beta C-hCG was detected in 42 (56.7%), levels ranging between 5.5 and 59.5 pmol/l (24.9 +/- 15.2).(ABSTRACT TRUNCATED AT 400 WORDS)


Delayed root canal therapy: an analysis of treatment over time. A retrospective study of 898 teeth receiving root canal therapy was performed to document the sequelae of delayed completion of root canal treatment. Teeth were categorized into a prompt treatment group and a delayed treatment group. Comparisons of prompt and delayed treatment groups were made with regard to preoperative pain, interappointment emergencies, postobturation pain, and final treatment. Findings from this study show that a palliative endodontic procedure is an extremely effective treatment. However, 56% of teeth with incomplete root canal therapy eventually were extracted compared with 2 to 3% for the root canal filling treatment groups. By emphasizing the potential loss of the tooth rather than the potential of interappointment emergencies, the clinician may be more effective in achieving compliance among patients receiving delayed treatment.


Monoclonal antibody ST1 identifies an antigen that is abundant in the axolotl and newt limb stump but is absent from the undifferentiated regenerate. Monoclonal antibodies (mAb) utilized in regeneration studies to date identify antigens that are up-regulated in the blastema. We obtained a monoclonal antibody, designated ST1 (Stump 1), that is reactive to an extracellular matrix (ECM) antigen exhibiting the opposite distribution; ST1 is an abundant antigen of the limb stump soft tissues but is absent from within the blastema. The border between abundance and absence of mAb ST1 reactivity was sharp and extended as a concavity into the stump. This distinct dichotomy led to further studies relevant to understanding how this extracellular matrix antigen is modulated during regeneration. mAb ST1 reactivity decreased in the internal tissues at the distal end of the limb prior to blastema formation and remained absent until the onset of differentiation. The initial decrease in mAb ST1 reactivity was dependent on the combined effects of injury and the wound epithelium but was nerve independent. At blastema stages of regeneration, the distribution of tenascin, ascertained by mAb MT1 reactivity, closely matched the area without reactivity to mAb ST1. The spatial and temporal distribution of the ST1 antigen in unamputated limbs and during regeneration did not correspond to any previously described ECM component.


Divalent cation conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum. The conduction properties of the alkaline earth divalent cations were determined in the purified sheep cardiac sarcoplasmic reticulum ryanodine receptor channel after reconstitution into planar phospholipid bilayers. Under bi-ionic conditions there was little difference in permeability among Ba2+, Ca2+, Sr2+, and Mg2+. However, there was a significant difference between the divalent cations and K+, with the divalent cations between 5.8- and 6.7-fold more permeant. Single-channel conductances were determined under symmetrical ionic conditions with 210 mM Ba2+ and Sr2+ and from the single-channel current-voltage relationship under bi-ionic conditions with 210 mM divalent cations and 210 mM K+. Single-channel conductance ranged from 202 pS for Ba2+ to 89 pS for Mg2+ and fell in the sequence Ba2+ greater than Sr2+ greater than Ca2+ greater than Mg2+. Near-maximal single-channel conductance is observed at concentrations as low as 2 mM Ba2+. Single-channel conductance and current measurements in mixtures of Ba(2+)-Mg2+ and Ba(2+)-Ca2+ reveal no anomalous behavior as the mole fraction of the ions is varied. The Ca(2+)-K+ reversal potential determined under bi-ionic conditions was independent of the absolute value of the ion concentrations. The data are compatible with the ryanodine receptor channel acting as a high conductance channel displaying moderate discrimination between divalent and monovalent cations. The channel behaves as though ion translocation occurs in single file with at most one ion able to occupy the conduction pathway at a time.


A model for ionic conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum. A model is developed for ionic conduction in the sheep cardiac sarcoplasmic reticulum ryanodine receptor channel based on Eyring rate theory. A simple scheme is proposed founded on single-ion occupancy and an energy profile with four barriers and three binding sites. The model is able to quantitatively predict a large number of conduction properties of the purified and native receptor with monovalent and divalent cations as permeant species. It suggests that discrimination between divalent and monovalent cations is due to a high affinity central binding site and a process that favors the passage of divalent cations between binding sites. Furthermore, differences in conductance among the group Ia cations and among the alkaline earths are largely explained by differing affinity at this putative central binding site.


Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current. The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior.