Abnormal development of the suprachiasmatic nuclei of the hypothalamus in a strain of genetically anophthalmic mice. In the anophthalmic mutant of the mouse the optic primordia are "genetically enucleated" well before the usual emergence of retinal ganglion cell axons (Silver and Hughes, '74). In eyeless animals, a portion of the mediobasal hypothalamus and one of its constituent nuclear pairs, nucleus suprachiasmaticus (SCN), were markedly abnormal in the embryo and adult. It has been reported that the ventral portion of the SCN receives a substantial, direct retinal innervation (Moore and Lenn, '72) and that these nuclei may mediate several light-induced hormonal and behavioral circadian rhythms (Stetson and Whitmyre, '76). During day 13 of mutant embryogenesis, just prior to the time of optic chiasm formation in normal animals, a large portion of ependyma and adjacent brain tissue herniated into the lumen of the would-be suprachiasmatic region of the third ventricle. In 70% of the animals examined histologically during the latter phase of development and as adults, regulation occurred and the brains were largely comparable with those of controls. However, in the remaining mutant mice, the overall size of either, or sometimse both, SCN was much reduced. The basal (but not the apical) dendrites of SCN neurons failed to develop fully. Some basal dendrites normally invade the optic chiasm below. In several mutant animals one or the other SCN had greatly increased numbers of cells, while the contralateral one had diminished numbers. These observations suggest that regular formation of the suprachiasmatic region of the hypothalamus and especially the suprachiasmatic nuclei, may depend during development upon the presence of the eye or the subjacent optic axons.


Ultrastructural basis of impulse propagation failure in a nonbranching axon. The morphological basis of intermittent conduction failure in the excitor axon innervating the crayfish opener and stretcher muscles was investigated using the electron microscope. The connective tissue component of the sheath surrounding the axon was found consistently to be thinner in the region at which blocking occurs than in control regions located one cm either proximally or distally, at which blocking does not occur. Otherwise in these regions differences in the width of the periaxonal spaces, the length or width of the mesaxons, the density of mitochondria, the width of the adaxonal glial cell layer, or the structure of lamination of the sheath are not observed. Because of the thinner connective tissue component of the sheath in the joint region, neighboring axons are distributed more densely around the excitor, and the volume of the extracellular space is reduced. The possibility that the reduced extracellular space might allow excessive accumulation of potassium during repetitive discharge, causing conduction block, is discussed. Alternative mechanisms consistent with this morphology are also considered.


Hyperphagia and obesity produced by parasagittal and coronal hypothalamic knife cuts: further evidence for a longitudinal feeding inhibitory pathway. Hyperphagia and obesity are produced both by parasagittal knife cuts through the medial hypothalamus and by coronal knife cuts through the posterior hypothalamus. The results of this study indicate that the two types of cuts produce their overeating effect by severing the same neural pathway. Experiment 1 demonstrated that unilateral parasagittal knife cuts combined with contralateral coronal cuts in either the posterior hypothalamus or the midbrain significantly increase food intake and body weight. Experiment 2 revealed that bilateral parasagittal cuts and bilateral coronal cuts in the hypothalamus produce qualitatively similar effects on food intake, diurnal ingestive pattern, finickiness, and amphetamine anorexia. The two types of cuts differentially altered water intake, however. In Experiment 3, coronal cuts in the posterior hypothalamus, like parasagittal cuts in the medial hypothalamus, were found to increase the food intake and body weight of rats previously given bilateral parasagittal transections through the lateral perifornical region. The neuroanatomy and neurochemistry of the longitudinal feeding inhibitory pathway suggested by these results are discussed.


Selenium in milk from feeding small supplements. Supplements of 0, 1, 2, or 5 mg of selenium from sodium selenite fed per cow daily from 90 days prepartum through approximately 6 mo of lactation had no significant effect on selenium in milk of Hereford cows. Selenium in milk was assayed 2 to 3 days postpartum (average of .014 to .023 ppm) and approximately 3 mo post parturition (average of .016 to .021 ppm). The basal diet consisted of medium quality grass-legume hay (.069 mg/kg), ad libitum liquid supplement (.152 mg/kg), and 1.36 kg shelled corn (.018 mg/kg) starting in early lactation. Treatments of selenium were administered via free-choice liquid supplement.


Use of urea by early postpartum Holstein cows. Thirty-nine lactating Holstein cows were fed high-energy complete rations ad libitum with crude protein: 1) 11.7% (negative control); 2) 13.9% (1% urea); 3) 16.6% (1% urea); or 4) 16.6% (positive control) in a continuous 12-wk study beginning at wk 5 postpartum. Milk production of 27.7, 31.8, 34.0, and 30.4 kg/day showed the use of urea nitrogen by groups 2 and probably 3. Two digestion-nitrogen balance trials with each cow also provided evidence that urea nitrogen was used for milk secretion. Energy digestibility averaged 59.4, 64.2, 65.4, and 65.8; and lower for the negative control diet. Nitrogen solubility in the diets was 28, 36, 32, and 21%, which reflects the objective of selecting ingredients with low nitrogen solubility for use in urea diets. Concentrations of ammonia nitrogen before and after feeding were 1.1, 3.3, 3.5, 4.2, and 2.2, 11.2, 11.9, and 9.3 mg/100 ml of rumen fluid. The prefeeding amounts were probably too low for maximum microbial growth. Urea-nitrogen concentrations in plasma were 8.65, 10.32, 18.00, and 17.03 mg/100 ml. These results lend support to the postulate that lactating cows in early lactation can use urea nitrogen when high-energy complete rations with ingredients of low nitrogen solubility are fed ad libitum.


Behavior of lactating dairy cows during total confinement. Daytime activity of four lactating Holstein cows housed in total confinement in stanchion stalls for about 14 wk was observed continuously, and activities such as eating, drinking, resting, ruminating, and socializing were recorded. Observations were by closed-circuit television and a switch panel connected to an event recorder. During the 15 h of daytime, the cows spent an average of 45% of the time lying, 26% eating, 22% ruminating, 1% drinking, and 2% socializing. Most eating occurred during standing (98.4%) while most rumination occurred during lying (59%). The distribution of these activities by time of day was similar to that of pastured dairy cows. Periods of eating, drinking, and social activity were most intense during and shortly after the morning and afternoon milking and feeding times. Conversely, periods of greatest recumbency, rumination, and rest occurred between feeding time from midday to late afternoon. Thus, in spite of prolonged total confinement, the four cows continued to exhibit behavioral activities (duration and distribution) which are typical of less confined cattle.


A technique for measurement of methylmalonic acid in cattle urine. Methylmalonic acid was measured in cattle urine by decarboxylating it to propionate with sulfuric acid and heat and quantifying the propionate so formed by gas-liquid chromatography. Crystalline methylmalonic acid added to cow urine was recovered quantitatively.


Tumor conference No. 13. Fatal amelanotic nodular melanoma in a 15-year old girl. The patient was a 15-year-old girl who was found to have a amelanotic nodular melanoma on a leg. The local malignancy was widely excised and an elective lymph node dissection was performed. On microscopic examination of the removed inguinal lymph nodes, one showed metastatic involvement. She was free of obvious disease for slightly more than one year at which time a subcutaneous metastasis was found on the chest wall. Soon thereafter she suffered dissemination of malignant melanoma and, despite systemic chemotherapy, rapidly deteriorated and died of metastatic melanoma one year later. The salient features of this patient are: (1) the onset of malignant melanoma early in life (age 15); (2) the poorer prognosis of amelanotic melanoma; (3) the often hopeless situation once distant metastases appear.


The management of pressure sores.

The management of pressure sores. The authors review their clinical experience in diagnosis and management of over 2,500 cases of pressure sores, of which more than half (1,351) required surgical operations. Pressure sores have been classified in 4 grades, a classification that the authors believe is helpful in planning treatment. Different conservative regimens of management are given. Surgical operations are tabulated. Pre- and postoperative management is especially stressed.


A practical approach to preparing children for dermatologic surgery. This paper presents a series of stratagems designed to minimize the potential psychological problems of children who require dermatological surgery. After discussing the "normal" critical periods of childhood, the selective approaches to children at different ages are presented. General and specific suggestions are made for pre- and postoperative management for both office and hospital surgical procedures.


Acanthoma fissuratum cutis. Report of a case and a review of previous cases. Acanthoma fissuratum cutis is a benign cutaneous lesion apparently caused by constant minor trauma. In the case here reported it seemed to have been caused by poorly fitting spectacles. Since a lesion of this type may be mistaken for a basal-cell epithelioma, its accurate diagnosis will spare the patient needless surgery and expense.


Unpredictability of theophylline saliva measurements in chronic obstructive pulmonary disease. The use of saliva as an indirect, non-invasive method of theophylline plasma level measurement was evaluated in 23 older men with chronic obstructive pulmonary disease and numerous concurrent medical problems. Simultaneously collected plasma and saliva samples were obtained on two or more occasions and analyzed for theophylline concentration by the Schack and Waxler spectrophotometric method. The mean (+/- SD) plasma:saliva ratio for 84 sample sets was 1.6 (+/- 0.5) with the saliva concentration averaging 64.8% (+/- 20.8%) of the plasma concentration. Multiplying a randomly chosen plasma:saliva ratio from each patient by the saliva concentration of a second randomly selected observation resulted in a predicted plasma concentration that differed by more than 20% of the measured concentrations for 16 of the 23 patients. Thus, use of saliva theophylline measurements obtained by the Schack and Waxler method to adjust dosage regimens cannot be recommended in these patients.


The uniqueness of hair transplantation in black patients. The author presents his own observations on hair transplant procedures in black patients. With slight modifications in the manner of obtaining donor autografts, the integrity of the hair shafts and papillae are maintained. Genrally, the aesthetic results are comparable to those obtained in white patients and often are achieved with considerably fewer autografts.


Extirpation of warts by a loop electrode and cutting current. Warts are a common dermatologic problem. Electrodesiccation has been the recommended surgical approach for therapy. An alternate method utilizing a wire loop electrode and cutting current is presented. The authors feel it is the surgical treatment of choice for most warts.


A study of some innovations in hair transplanting. The value of 1) cooling of plugs to induce a shorter "resting phase", 2) power-driven punches to produce a greater yield of hair per graft; and 3) larger grafts to produce a greater yield of hair has been studied. Cooling does not appear to shorten the "resting phase." Power-driven punches produce an insignificant increase in the number of hairs yielded per graft. Using larger "standard" grafts does not lead to an increased yield of hair per graft and results in an overall decrease in yield from donor areas.


Asthma in the South Bronx: clinical and epidemiologic characteristics. This study of the adult emergency room asthma population in an urban poverty area was performed to assess and enhance the effectiveness of medical treatment and community health care delivery. The number of visits for acute asthma decreased during the 3-yr period of observation despite an annual increase in the total number of emergency room visits. This was attributed to fewer multiple visits and earlier hospitalization. An analysis of adult and pediatric patients hospitalized for asthma was also performed and revealed that asthma was responsible for 25% of pediatric and 13% of adult female medical admissions. An asthma registry of 1,329 adult patients, compiled over a 12-mo period showed a 7:3 female to male ratio of 60% Puerto Rican predominance. The identification of patients usually refractory to outpatient treatment was hindered by the constant flux in the population base as illustrated by an 85% increase in the asthma registry over the succeeding 12-mo period. Since many of these patients were previously cared for at other metropolitan institutions the creation of a centralized data system making such records available to all emergency care facilities would allow for the rapid identification of refractory patients and enhance the management of their acute episodes.


Contribution of foodservice programs in preschool centers to children's nutritional needs. Seven-day nutrient intakes of 517 Head Start and day care children participating in USDA's Special Food Service Programs for Children in Nebraska, Kansas, and Texas were assessed. Protein, vitamin A, and ascorbic acid levels from diets served at the centers were judged to be adequate, while calories and B vitamins were below recommendations but proportional to each other. Calcium intake from center diets did not increase proportionately as the number of meals and snacks increased. Nutrient contributions were only slightly greater from center diets when two meals and two snacks were provided than when one meal and one snack were served. Home diets made substantial contributions to the diets of all children, resulting in little difference in total nutrient intakes between children receiving fewer or more meals and snacks at the centers. Iron was the nutrient supplied in least amount in relation to recommendations, when intakes from home and center were combined.


Nutritional indexes of clients in a maternity and infant care project. I. The target population. The Detroit Maternity and Infant Care Project (DMICP) is funded under Title V of the Social Security Act. Records of 198 pregnant women and their infants seen by a project nutritionist in fiscal 1971-72 were studied. The women were predominantly young (below twenty years of age), black, and not enrolled in school. Most were pregnant for the first time. About a third were overweight. Mean scores on the APGAR scale for the infants at birth were high (7 to 10). More than half of these young mothers brought their infants to the project center for check-ups six to ten times during the first year.


Nutritional indexes of clients in a maternity and infant care project. II. Dietary, anthropometric, and hematologic indexes of pregnant women and their infants. Low intakes by 198 pregnant women of milk, fruit, and vegetables are reported: consumption of meat and bread and cereals was satisfactory. However, mean hemoglobin and hematocrit values were within acceptable ranges for these women, indicating that supplementation apparently compensated in part for poor dietary habits. Protein intake of the infants of these mothers was above recommendations, the advisability of which is questioned. Height and weight of the male and female infants at birth were above and below the 10th percentile, respectively. By the age of four months, however, all infants were equal to or above this level. Mean hemoglobin levels were above acceptable levels.


Nutritional indexes of clients in a maternity and infant care project. III. Relationships between developmental, medical, and nutritional variables. Nutritional and medical records of the infants of 198 women of a low socioeconomic group were correlated with results of the Denver Developmental Screening Test. At one year, the infants' developmental age was above the norm. In addition, selected medical, nutritional, and developmental variables, as indicated by charts of the Detroit Maternity and Infant Care Project, were statistically analyzed for interrelationships. No correlation was found between hemoglobin levels, even though they were low for some infants, and developmental indexes. Prenatal weight gain of the mothers was statistically significant in relation to their infants' birth weight, height, and head circumference. Thus periodic monitoring of weight throughout pregnancy is recommended.


Meat-buying practices of Caucasians, Mexican-Americans, and Negroes. Meat purchases were observed at supermarket checkout counters, socioeconomic data were obtained by questioning shoppers, and card questionnaires were given to 600 shoppers. Two supermarket chains in each of the three ethnic areas of Lubbock, Texas, were used on two days. Ethnic group was significantly related to the choice of half of the twelve meat cuts bought by the greastest number of shoppers and accounted for more significant effects on meat-buying variables than did chain, area, and day. Returned card questionnaires were 77 per cent accurate concerning meat-buying data.


Conventional vs. formulated foods in school lunches. II. Cost of food served, eaten, and wasted. School lunches containing all conventional foods were designed to provide one-third or one-half the recommended allowances for elementary students. The same nutrient levels were planned in meals containing some formulated items. Each type of meal was served for five days, and total food costs and costs of food served, consumed, and wasted were calculated. At the same nutritional level, mean preparation costs of partially formulated meals were lower than for meals composed of all conventional foods. Meals providing one-half the allowances and containing formulated items cost slightly less than totally conventional meals which provided one-third of the allowances. Cost of waste was lower with partially formulated meals.


Three score and ten plus more.

Three score and ten plus more. The elderly in our society are required to make many social and psychologic adjustments. In addition, they have to cope with the inevitable physiologic changes associated with the aging process. These alterations in lifestyle and in body functioning call for modified dietary patterns during this phase of life. In particular, older persons should reduce caloric intake while maintaining a highly nourishing diet. Other recommended dietary modifications include a shift toward smaller meals eaten more frequently, and the use of generous amounts of fiber and liquid to avoid constipation. As a result of growing community awareness, some programs have been started to assist the elderly in overcoming problems that may cause poor nourishment.


Relation of long-term electronic cardiac pacing to mental status and adaptation in the institutional aged. The long-term effects of cardiac pacemakers on the mental status and adjustment of an aged population were investigated. In an institution for the aged, 25 residents (average age, 85) in whom pacemakers had been implanted for an average of 53 months were compared to 18 residents of the same age and sex who had a slow heart rate. A semistructured interview was given to determine mental status, affective condition, perceived health, and other concerns. Cardiac status was rated for all subjects according to the criteria of the New York Heart Association. By the measures of adjustment and mental status, no differences were found between pacemaker patients and those with a slow heart rate. Cardiac status was somewhat poorer in the pacemaker group. When comparison was made between the pacemaker patients with uncompromised or only slightly compromised cardiac status and subjects with a slow heart rate and similar cardiac status, no significant differences were found in the foregoing measures. These findings suggest that although there may be changes in functioning in the acute phase following implantation of a pacemaker, there are no long-term effects on adjustment in subjects of advanced age. Adaptation in an institution for the aged may be more related to personality factors than to specific health problems.


Testing as a component of continuing education programs: evaluation of conference presentations by this method. As a means of evaluating the effect of each presentation at a national medical conference and of the meeting as a whole, the scheduled lecturers were asked to supply the testers with several questions that summarized the most important points of their talks. Audience participants at the meeting were given tests drawn from these questions--one test before the beginning of the meeting, and another at the end. The results were compared for the answers to each lecturer's 3-question group, and for the complete tests. All scores were better at the end than at the beginning of each lecture. A follow-up survey of the attitudes of participants showed a positive reaction to the use of such testing at future meetings.


Perceptions of urban versus rural hospital patients about return to their communities. During a two-month period in 1976, male patients scheduled to be discharged from two Veterans Administration Hospitals, who were aged 55 or older, chronically ill, able to communicate rationally, and had been hospitalized at least a week for the current illness, were interviewed prior to discharge. Information was sought regarding their feelings about admission and discharge, the availability of and their need for 13 related health-related services at home, and the informal support systems available to them in their local communities. Comparisons were made between patients from distinctly rural settings (communities with less than 5,000 population) and those from larger towns or cities. Both urban and rural patients were modest in assessment of their own health-related needs, especially their need for social and ancillary health services. In almost all instances, the perceived availability exceeded perceived needs. Rural dwellers reported somewhat less apprehension about entering the hospital; they also reported more social contact in their home communities despite the fact that in this sample the rural dwellers were more likely to be older, widowed, and living alone. Rural dwellers were slightly more likely to have their own family doctor.


Pupillary examination.

Pupillary examination. Examination of the pupils is an essential part of the evaluation of patients in optometric practice. In this article, the normal pupil and pupillary reflexes are reviewed, along with a discussion of anisocoria and specific anomalies of the pupils. Explanation of step by step office examination techniques is presented, as well as a discussion of the pathophysiology of abnormal pupils.


Essentials of slit lamp biomicroscopy.

Essentials of slit lamp biomicroscopy. Biomicroscopy is an indispensable part of the ocular health examination performed on every patient. The purpose of this paper is to briefly review the basic illumination technique so that the examiner thoroughly understands their uses and develops for himself a specific investigative procedure. This testing may progress from the lids and lashes to the anterior vitreous in a coordinated manner.


Tonometry in optometric practice -- the current status. The past two decades have seen enhanced optometric interest in tonometry and in other techniques to assess the ocular and/or general health status. This probably reflects several factors; an increasing role of the optometrist as a primary health care practitioner, the availability of better instrumentation for tonometry, and a far better understanding of the relationship between intraocular pressure and diseases from the group known as the glaucomas. This paper represents an attempt to provide information which may be helpful to the practitioner in determining what tonometer to use and how to utilize tonometric data most effectively.


Gonioscopy: evaluation and interpretation. Gonioscopy is the ocular health examination technique which offers to the practitioner the means to directly study the anterior chamber angle. Its uses are numerous and include glaucoma classification, predilation angle evaluation, and the presence of iris tumors, foreign bodies and anterior synechiae. Since a meaningful gonioscopic examination depends upon the examiner's recognition of the chamber landmarks, a detailed analysis of each structural element is presented. In addition, the techniques for performing gonioscopy with the popular lens types are viewed as is the system for interpretation and recording.


Fundus contact lens and Hruby lens.

Fundus contact lens and Hruby lens. The fundus contact lens is a much overlooked diagnostic aid that can make difficult diagnosis simple. The combination of binocular vision, great light intensity and a range of magnification powers using the fundus contact lens and the slit lamp give the practitioner an excellent resolution to view the fundus.


A suggested perimetric procedure for optometrists. Perimetry is one of the most important optometric tests for the detection of pathology associated with the visual system. The fact that perimetry may be the only means of discovering certain serious abnormal conditions dictates its routine use on every patient. Suggested procedures for central and peripheral field charting as well as screening techniques are given for some selected commonly used instruments in perimetry.


Photodocumentation.

Photodocumentation. Ocular photography is an invaluable adjunct to complete, clinical optometric care. It is an easy and accurate method of documenting and following ocular anomalies and contact lens patients. This article describes the basic types of ocular photographic systems and their uses.


Sphygmomanometry.

Sphygmomanometry. Hypertension is a major health problem in America today, affecting one in every six adults. The problem is that one-third of those with the disease do not know it. Optometry's role as a primary provider of health care must include screening procedures (sphygmomanometry) for hypertension.


A rapid GC method of monitoring Mesurol (4-(methylthio)-3,5-xylyl-N-methyl carbamate) and its sulfoxide and sulfone metabolites and their persistence in lowbush blueberries. A facile analytical procedure was developed for determining Mesurol (4-(methylthio)-3,5-xylyl-N-methyl carbamate) and its oxidation products in blueberries. It involved blending with acetone, partition with chloroform and derivatization with trifluoroacetic anhydride and quantitation by gas chromatography/flame photometric detector (GC/FPD). The method showed good recoveries for Mesurol and its sulfoxide at the 0.1 ppm level and Mesurol sulfone at the 0.3 ppm level with a 25 g sample. It was applied to monitor levels of the insecticide and its oxidation products on field-treated blueberries. The sensitivity of the method may be increased 5-fold by the inclusion of a clean-up step. The optimal conditions for the detection of Mesurol TFA by the modified Bendix sulphur/phosphorus emission detector operating in the sulphur mode required an oxygen/hydrogen ratio of 0.38, for a column flow of 60 ml/min. The minimum detectable amounts of the TFA derivatives of Mesurol, its sulfoxide and sulfone were calculated as 1.3, 2.3 and 5.8 X 10(-11) g/sec, respectively.


The vascularization of human flexor tendons within the digital synovial sheath region--structureal and functional aspects. The intrinsic vascularization of human flexor tendons within the digital sheath region was studied on fresh amputation specimens with the aid of angiographic and histochemical techniques. In the flexor digitorum profundus tendon, three separate vascular systems of various origin and with no or very little communication could be verified. In the flexor digitorum superficialis tendon, two such systems were observed. The volar surface of both tendons is more or less devoid of vessels. Moreover, at the proximal interphalangeal joint level, the flexor digitorum profundus tendon has a volar avascular zone, constituting about 1 mm, i.e., about one-third to one-fourth of the thickness of the tendon. It is assumed that the synovial fluid is of importance for the nutrition of the tendons and that therefore the synovial sheath should be preserved as much as possible.


Primary tendon healing: a review.

Primary tendon healing: a review. Clinical and experimental studies on primary tendon healing are reviewed and correlated. Emphasis is placed on the importance of blending the extratendinous and intratendinous elements of tendon healing to obtain optimal functional results. Studies which demonstrate the ability of tendon cells to metabolize, proliferate, and secrete collagen when isolated from paratendinous tissue are cited along with those which demonstrate the importance of the microcirculation of the tendon in tendon healing. Those factors which interfere with intratendinous healing are discussed, such as invasive suture techniques, tension on the area of repair, and interference with segmental blood supply within zone II. The importance of the synovial sheath and synovial fluid in nourishing tendon cells and the effect of ischemia in stimulating the ingrowth of adhesions are brought out. Discussion includes such factors involved in the postoperative management of tendon repairs as those which affect the strength of tendon repairs and quantitative and qualitative methods of modifying adhesion formation.


Flexor tendon graft through intact superficialis tendon. During a 14-year period, the flexor profundus mechanism was reconstructed with a free tendon graft in 25 fingers. The graft was passed either through or alongside the intact superficialis tendon. Five of the profundus tendons had ruptured, and 21 had been severed. One patient was under 10 years of age and only three were over 21 years of age. The result was considered to be satisfactory if the finger flexed to 3.2 cm or less of the mid-palm, had at lease 20 degrees of voluntary flexion of the distal joint, and lacked no more than 30 degrees of extension of the proximal interphalangeal joint. Additionally, to be satisfactory, the combined loss of extension of the proximal interphalangeal and distal interphalangeal joints ahd to be 40 degrees or less for an index or middle finger, and 60 degrees or less for a ring or little finger. Using these criteria, 20 patients were satisfactory, four were unsatisfactory, and one was unchanged. Selected patients who are between the ages of 10 and 21 years will benefit from this operation, providing that the finger had limber joints and minimal scar, and the superficialis tendon flexes the proximal interphalangeal joint at least 80 degrees.


The role of flexor tenolysis in the palm and digits. Seventy-seven digitis in 70 patients undergoing a technique of thorough flexor tenolysis, with instillation of local triamcinolone, and immediate motion were studied. Classification of the results utilized a method which determined the percentage of passive joint flexion potential actively achieved and by a second system which graded the results in the finger as a whole. A further categorization into three patient groups, depending on the etiology of the tendon adhesions, was carried out. Using these classifications 84% or the proximal interphalangeal joints, 86% of the distal interphalangeal joints, and 80% of the fingers as a whole were improved by this procedure. These results were comparable or superior to those of other published reports. Improvement in digital flexion was consistent, often with restoration of near-normal function. The incidence of tendon rupture, infection, and delayed wound healing have not been great.


Transmetacarpal amputation of the index finger: a clinical assessment of hand strength and complications. A clinical study of hand strength and complications in 41 patients with a transmetacarpal amputation of the index finger found that the average prehension strength was reduced by 20% and stability of grip by almost 50%. Tendon transfers or other operative modifications did not affect the results. The most disabling complication, hyperesthesia, or painful sensitivity to light touch, in the thumb--long-finger web was present in 59% of patients and interfered with hand function in 37%.


Radial artery cannulation in 1,000 patients: precautions and complications. A review of 1,000 radial artery cannulations performed over a 2-year period showed that, with careful selection of patients, by means of the Allen test and Doppler studies, and with the apparatus used, only two serious complications were encountered; embolectomy was necessary in one and arterial reconstruction in another. Twenty-four percent of patients had evidence of diminution of flow, but in none did it persist for more than 2 weeks. Critical factors in reducing complications were a short period of cannulation, use of a Teflon catheter, and a continuous arterial line flush system.


Strain differences in the prealbumin serum esterases of JAX rabbits. The serum prealbumin esterase phenotypes were determined for 431 adult rabbits representing the majority of the breeding stock of the genetically defined JAX rabbits. Uniform phenotypes were observed in 8 of the 15 strains where adequate samples were obtained. In all of the phenotypes where uniformity was observed, the Est-2F gene was lacking. Also, all 431 rabbits lacked the Est-3D allele commonly observed in Europe. A sex difference was seen in the f' zone, which was darker in females than in males when the staining process was twice the normal length of time.


Characterization of antral gastrin cells with region-specific antisera. A number of gastrin antisera, which in radioimmunoassay systems showed no or negligible cross-reactivity towards the structurally and functionally related peptide cholecystokinin were found to react with both gastrin and cholecystokinin cells when used for immunocytochemistry. This discrepancy was shown to be due either to reactivity against a COOH-terminal region common to gastrin and cholecystokinin or to the occurrence of heterogenous antibody populations in the antisera. By differential absorptions the latter type of antisera could be rendered specific for gastrin. Antisera reactive against the NH2-terminal, middle or COOH-terminal regions of human heptadecapeptide gastrin were prepared and together with a specific cholecystokinin antiserum used for the characterization of antral gastrin cells of different species. The results indicate that only the COOH-terminal region of gastrin is conserved during evolution.


Response of the lysosomal system of the corneal epithelium to tyrosine-induced cell injury. Rats fed excess tyrosine develop corneal epithelial disease which parallels that found in humans with tyrosine aminotransferase deficiency (tyrosinosis). In the rat, focal lesions develop within the central epithelium and contain crystals (presumably tyrosine) that disrupt cells. We have studied these lesions and localized acid phosphatase and aryl sulfatase at the electron microscope level. Within 60 hr after initiation of diet, cells within the lesions showed an increase in lysosomal enzyme activity. This activity was localized inside some of the crystal ghosts and in numerous lysosomes, including autophagic vacuoles and multivesicular bodies. After 84 hr on diet the entire central corneal epithelium was disrupted and polymorphonuclear leukocytes had infiltrated the area. Crystals were phagocytosed by or developed within polymorphonuclear leukocytes. We hypothesize that crystals form within epithelial cells, disrupt first their lysosomes, and then cells, leading to externalization of lysosomal enzymes. This extracellular lysosomal enzyme release may be responsible for the acute inflammatory response that ensues.


Studies of the human sex ratio and factors influencing family size in Botucatu, Brazil. During 1974--75, data on sex and family size were obtained from approximately 500 Brazilian college students and their parents. Sex ratios for the immediate and parental generations were 107:100 and 106:100, respectively. Correlation coefficients were calculated between sexes of various children in families of the immediate generation. A significant positive relationship was found between sexes of the first two children in families of two or more children. The overall correlation between sexes of successive births was positive but not significant. Correlation coefficients between sexes separated by one or more births were not significant. The observed frequencies of combinations of sexes within the various family sizes did not differ from expected frequencies. Average numbers of children per family were 4.39 and 6.80 for the immediate and parental generations, respectively. Average family sizes decreased as the formal educational level of the parents increased. If the parents' desired both sexes of children, such preferences had no measurable influence on family size.


Electron microscope immunohistochemical localization of substance P in the central nervous system of the rat. Substance P is an undecapeptide that is distributed in many areas of the central nervous system. In order to clearly identify the structures and organelles containing substance P, an immunohistochemical localization of this peptide was performed at the ultrastructural level. Substance P was detected in dense core vesicles of many nerve endings in both the amygdaloid nucleus and the substantia gelatinosa of the spinal cord. These findings support the hypothesis that substance P could act as a neurotransmitter.


Male preference and family size.

Male preference and family size. The influence on family size of the sex of the first children was studied in a sample of 1851 families of students in Sevilla University. Significantly more families limited family size to two or three children when the two or three children were of the same sex than in the opposite case. Significantly more families limited family size to three children when not all the three first children were females. The frequency of families having more than three children is not increased to a larger extent when the three first children are males than in the other cases.


Morphogenesis and morphology of the brain stem nuclei of Cetacea. I. The hypoglossal nucleus. 1. The hypoglossal nucleus of whalebone whales is composed of four major subdivisions, forming four parallel columns, here called the dorsomedial, the dorsolateral, the ventromedial and the ventrolateral XII columns. 2. The ventromedial XII column extends throughout the hypoglossal nucleus, forming in whalebone whales the rostral as well as the caudal end of the nucleus. 3. The ventrolateral XII column is lamelliformed and splits into a dorsomedial and a ventrolateral part, the former intimately related topographically to the dorsomedial column. 4. The dorsomedial XII column is torpedo-shaped, tapering in rostral direction and terminating a little short of the rostral end of the ventromedial XII column, while the blunt end terminates immediately caudal to the obex. 5. The dorsolateral XII column is the shortest subdivision, approximately one fourth of the length of the entire hypoglossal nucleus. The blunt rostral end of the torpedo-shaped column blends with the dorsomedial XII column, its tapering caudal end terminating rostral to the obex. 6. The cells of the hypoglossal nucleus vary in size from small to medium-sized and large, the small ones dominating in the dorsomedial, the large ones in the dorsolateral and ventromedial XII columns. The ventrolateral column is characterized by spindle-shaped cells. 7. In the toothed whale Phocaena communis the differentiation of the hypoglossal nucleus is less clearcut than in whalebone whales, but a similar structural priniciple is recognizable.


Failure of chronic exposure to nonthermal FM radio waves to mutate Drosophila. A stock of Drosophila sc VI - YS/y ac oc ptg - YL/y ac oc ptg - YL/y sc S1 B In49 ct ns v sc8 that accumulated the recessive lethals on the X chromosome was exposed to a frequency of 98.5 MHz (wave length 3.35 m) and a field strength of 0.3 V/m. The flies were kept near the base of the 300-ft antenna of a 50,000 watt transmitter for 32 weeks. There was no significant difference in the percentage of lethals between the stock exposed to 4,020 hours of nonthermal FM radio waves and the controls.


[Investigations on the basal dendritic tree of lamina-V-pyramidal cells in the visual cortex of rats after destruction of the lateral geniculate body and after dark raising (author's transl)]. The basal dendritic trees of the lamina-V-pyramidal cells of rats were investigated after 1th unilateral destruction of the dorsal lateral geniculate body (Cgld) 2nd dark raising I. Animals with destroyed Cgld. Comparing the data of free dendritic terminations (FDE), branching points (VZP), number of segments (AdD) and length of segments (LdD) no significant differences have been remarked between--controls of the same litter (non-influenced side),--influenced sides of animals of the same litter. A significant difference between the ipsi- and contralateral hemispheres of animals with unilateral geniculate destruction. II. Dark raised animals There were no significant differences between dark raised animals, their controls and between dark raised animals and controls. The causes of postoperative changings have been discussed. Mainly retrograde degeneration effects may be responsible for the ascertained differences.


The effect of public policies on the demand for higher education. A binomial logit model is fitted to the college attendance behavior of 27,046 male high-school juniors in 1960, divided into 20 subgroups defined by student ability and family income. Tuition, high admissions standards, travel costs, and room and board costs all have significant negative effects on attendance. The highest elasticities of demand are found to occur in the low-income strata and lower-middle ability quartile, suggesting that an efficient subsidy program should focus on these groups. Coefficients of forgone earnings and measures of the local payoff to college attendance are small but generally have the expected sign.


The antipoverty effectiveness of in-kind transfers. In recording its poverty statistics, the U.S. Census Bureau ignores the impact of in-kind transfers on the extent of poverty. In this paper, we estimate that when in-kind food, housing, and medical care transfers are counted and measured at their cash-equivalent value, and when Census income is adjusted for underreporting, federal taxes, and intrahousehold income-sharing, the 1972 poverty count and the poverty gap are halved. In addition, we find that in-kind transfers are relatively inefficient devices for reducing income poverty, delivering only about 31 cents of anitpoverty effect per dollar of program cost.


Population genetics of Aa and Ab immunoglobulin allotypes in wild rabbits of south-eastern Australia. I. Allotype frequencies. Aa and Ab allotype frequencies have been investigated in wild rabbit populations throughout Victoria and South-east South Australia. The overall mean allele frequencies for thirty-three populations are 0-53:0-12:0-36 for a1:a2:a3 and 0-72:0-22:0-05 for b4:b5:b9. The b6 allele was not found anywhere. The a1 frequency has been found to increase in proportion to increases in mean annual rainfall. While considerable variations exist in allotype and allele frequencies from area to area, the relationships a1 greater than a3 greater than a2 and b4 greater than b5 greater than b9 are almost always observed. The results are discussed in terms of the historical origins of Australian wild rabbits and possible genetic mechanisms to explain the maintenance of allotype 'hierarchies' in large populations breeding at random.


Segregation of HLA haplotypes in 100 families with a myasthenia gravis patient. An analysis of the HLA data of 100 myasthenia gravis (MG) patients and their first degree relatives and spouses is presented. The family studies confirmed the excess of B8 in the myasthenia gravis patients and showed that the excess was not limited to the A1, B8 haplotype. An excess of B8 homozygous patients was found from the matings of two B8 heterozygous parents, suggesting the existence of a dominant B8 linked MG susceptibility. B8 homozygous individuals run a 4-7 times higher risk of acquiring myasthenia gravis than B8 heterozygous individuals.


Gene expression of a region of chromosome 17 during murine spermatogenesis. The presence of H-2-linked gene products on spermatozoa and their time of appearance during spermatogenesis was determined. Thymus leukaemia antigen specificities 1, 2 and 3 could not be detected on spermatozoa by absorption of the antisera. Immunofluorescent studies with anti-Slp sera did not reveal any specific reactivity with target spermatozoa. In contrast, H-2D antigens were present on somatic as well as germ line components in testes so the time of their first appearance during spermatogenesis could not be precisely specified. Cell separation experiments indicate that H-2D antigens are present on pachytene spermatocytes and increased in quantity on spermatids. The sperm-specific isoenzyme of phosphoglycerate kinase, Pgk-2, appears at a later stage of spermatogenesis than do the H-2 region antigens.


PGM3 locus and its genetic polymorphism in lymphocytes of the pig. PGM3 activity was investigated by means of horizontal starch gel electrophoresis. In the pig of the German Landrace three different phenotypes have been recognized: F, S and FS. Family studies suggest the occurrence of at least two alleles--PGM3F and the PGM3S at an autosomal locus.


Rates of plasma porphyrin disappearance in fluorescent vs. red incandescent light exposure. The rates of porphyrin disappearance in plasma specimens were assessed during exposure to standard fluorescent room lighting. Protoporphyrin half-life in specimens from patients with erythropoietic protoporphyria appeared to be less than 30 min under these conditions. Uroporphyrin-coproporphyrin mixtures in plasmas of patients with porphyria cutanea tarda were more photostable, with half-lives measurable in terms of hours. All plasma porphyrins could be protected for several days from similar photodegradation by performing all blood drawing, processing, and assay procedures under ordinary red-incandescent illumination, and by storage in the dark.


Potentiation of itch and flare responses in human skin by prostaglandins E2 and H2 and a prostaglandin endoperoxide analog. The itch and erythematous responses induced by intradermal injection of prostaglandin E2 (PGE2), the unstable prostaglandin endoperoxide PGH2 (t1/2 approximately 5 min at 37 degrees C) and the stable endoperoxide analog (15S)-hydroxy-9alpha, 11alpha-(epoxymethano)prosta-5,13-dienoic acid (EPA) were studied in volunteers. The compounds were given alone or in combination with histamine. All the compounds produced flare reaction in the skin; the order of potency was PGE2 greater than PGH2 greater than EPA. PGE2 and PGH2 evoked a sensation of itch in about half of the subjects whereas the same doses of EPA gave no itch response. In combination with histamine all compounds elicited itch of longer duration and flare of larger area than could be accounted for by simple additive effects of any released histamine. The results indicate that the PGs and PG intermediates formed in skin may potentiate the pruritogenic and flare-inducing effects of inflammagens in man.


Induction of hyphae in cultures of Pityrosporum by cholesterol and cholesterol esters. The effect of cholesterol and cholesterol esters on Pityrosporum cultures has been studied. A mixture of 0.25% to 2.0% of cholesterol:cholesteryl stearate:glyceryl monostearate (2.0:1.5:2.0) added to Bacto Yeast Morphology Agar plus oleic acid was able to induce hyphae in cultures of both Pityrosporum orbiculare and P. ovale. This result is discussed with respect to the cholesterol effect on cell membranes and to the occurrence of cholesterol and cholesterol esters in the scaling patches of Pityriasis versicolor.


In vitro studies on the protoporphyrin uptake and photosensitivity of normal skin fibroblasts and fibroblasts from patients with erythropoietic protoporphyria. Fibroblasts derived from patients with erythropoietic protoporphyria (EPP) are not sensitive to violet light and do not contain an excess of protoporphyrin (PP). Fibroblasts from both normal individuals and patients with EPP can take up very low concentrations of PP from culture medium. Cells grown in PP-containing medium showed a gradually increasing but limited uptake of PP and also an increased sensitivity to light. A sensitive scanning microfluorometric method has made it possible to demonstrate that the PP is mainly localized in the perinuclear granules. After exposure to violet light, cells photosensitized by PP in a culture medium showed increased membrane permeability as well as reduced reproductive capacity. Both of these photodamage effects can be repaired during postirradiation incubation in culture medium at 37 degrees C.


Evaluation of a UDP-glucose-4-epimeraseless mutant of Salmonella typhi as a liver oral vaccine. A mutant (Ty21a) of Salmonella typhi, which lacks the enzyme uridine 5'-diphosphate-glucose-4-epimerase, was evaluated in volunteers for use as a live attenuated oral typhoid vaccine. Five to eight doses of vaccine (containing 3-10(10) viable organisms per dose) were given to 155 men without significant side effects. The rate of excretion of the vaccine strain in stools was low, and the majority of isolations occurred on day 1 after vaccination. Revertants able to fement galactose were not found in any of 958 stool isolates tested. The mutant, strain Ty21a, grown in brain-heart infusion broth (BHIB) with 0.1% galactose, produces more O side chain than the same vaccine strain cultivated without galactose. Volunteers vaccinated with strain Ty21a grown in galactose and then challenged with 10(5) virulen S. typhi were significantly protected from disease and also had decreased stool carriage of S. typhi as compared with controls. Strain Ty21a grown without galactose did not provide vaccinees significant protection nor decrease fecal excretion of S. typhi as compared with controls. Strain Ty21a, when grown in BHIB with 0.1% galactose, results in a safe, stable and protective oral vaccine that warrants further study in field trials.


Antileishmanial effect of allopurinol. II. Relationship of adenine metabolism in Leishmania species to the action of allopurinol. Allopurinol was shown to be effective in vitro against Leishmania mexicana and Leishmania donovani as well as against Leishmania braziliensis. The major metabolic derivative of allopurinol in humans, oxipurinol, also is antileishmanial for L. donovani. The antileishmanial effect of allopurinol and oxipurinol can be specifically reversed by adenine, and its metabolic precursors and derivatives, but by no other purines or their derivative. It is proposed that the adenylosuccinate synthetase or the adenine phosphoribosyltransferase may be sites of action for these agents.


Immunoepidemiology of meningococcal disease in military recruits. II. Blocking of serum bactericidal activity by circulating IgA early in the course of invasive disease. The potential role of IgA antibody to Neisseria meningitidis, which blocks bacteriolysis by IgG and IgM, in producing the susceptible state in military recruits, a population at greater than expected risk, was investigated in 28 patients with meningococcal disease. IgA was removed from acute-phase sera by immunoadsorption; IgG was separated by ion-exchange, and IgM by gel-filtration chromatography. The bactericidal activity of acute-phase sera, before and after removal of IgA, and of IgG and IgM fractions from the sera, was tested against each of the homologous infecting strains. Bactericidal activity, the correlate of protective immunity, was deficient in 24 of 28 unabsorbed sera, but uniformly present after the removal of IgA in a median titer of 1:16. IgM accounted for all or nearly all of the bactericidal activity. IgG was largely inactive. Susceptibility to meningococcal disease may be affected by the blocking of bactericidal IgM by circulating IgA.


Efficacy of live attenuated influenza A/Scotland/74 (H3N2) virus vaccine against challenge with influenza A/Victoria/3/75 (H3N2) virus. For evaluation of heterologous protection by live attenuated influenza virus vaccine, 42 healthy volunteers with low titers of or no antibody to A/Scotland/74  (H3N2) and A/Victoria/3/75 (H3N2) influenza viruses were given live attenuated A/Scotland/74 (H3N2) virus vaccine or placebo by the intranasal route with no resultant vaccine-related illness. Seventeen of 21 vaccine recipients and none of 21 placebo recipients developed antibody conversion. Thirty-seven days after administration of vaccine or placebo, all subjects were challenged intranasally with wild-type A/Victoria/3/75 influenza virus. Five placebo recipients and no vaccine recipients developed moderately severe illness, whereas 10 vaccine recipients and three placebo recipients developed no illness (p less than 0.025). Although 16 of 21 vaccine recipients fulfilled criteria of infection with the challenge virus, shedding of virus was significantly less frequent, less prolonged, and of significantly lower magnitude than that in the placebo recipients. Thus, live attenuated influenza virus vaccine showed a significant protective effect against illness following challenge with heterologous wild-type virus. The protective effect and the negligible side effects of this vaccine merit consideration of its use in a large-scale field trial.


Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics. A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins. At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol. Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus. Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described.


Effect of hemoperfusion of clearance of gentamicin, cephalothin, and clindamycon from plasma of normal dogs. Nine normal dogs were divided into three groups of three. Group 1 was given an overdose of gentamicin; group 2, cephalothin; and group 3, clindamycin. Group 1 had hemoperfusion with Amberlite XE-336, and groups 2 and 3 with Amberlite XAD-4 resin adsorbents, for 6 hr with a blood flow rate of 300 ml/min. The plasma clearance and removal rates of antibiotics by the hemoperfusion columns were high. The clearance rate of gentamicin from plasma (mean +/- standard deviation) ranged from 59 +/- 30 to 199 +/- 6 ml/min, of cephalothin from 66 +/- 14 to 157 +/- 8 ml/min, and of clindamycin from 55 +/- 9 to 125 +/- 16 ml/min. Of the total dose of antibiotic administered, the hemoperfusion columns removed 67% from theplasma in group 1, 41% in group 2, and 18% in group 3. The fact that antibiotics may be rapidly removed from the blood during hemoperfusion should be considered in calculation of the therapeutic dose of antibiotic required for patients who receive this preocedure. Also, hemoperfusion can effectively and rapidly remove certain antibiotics from the blood of patients who have had a potentially toxic overdose.


Characterization of pyruvate kinase from the liver of a patient with aberrant erythrocyte pyruvate kinase, PK Nagasaki. The characterization of the L-type PK were made of PK extracted from the liver of a patient with congenital hemolytic anemia associated with an erythrocyte PK variant, PK Nagasaki. The L-type PK of PK Nagasaki showed the following parameters: slow migration on electrophoresis, high Km for PEP without F-1,6-P2, less activation by F-1,6-P2, normal Km for ADP, high utilization of UDP, acidic pH optimum, and instability to urea and heat. These tests served to differentiate this L-type PK variant from the other variants previously reported. At the same time, both the Km for PEP with F-1,6-P2 saturation and the electrophoretic mobility of L-type PK were found to be different from those of the erythrocyte PK and PK Nagasaki. Though the liver cell, with regard to L-type PK, has only the less functional and less stable mutant L-type PK there is no evidence of liver dysfunction or damage, although there is chronic hemolytic anemia.


Enhancement of K transfer to intracellular fluid by cerebral artery K-loading. Intact, UL, and pancreatectomized UL dogs were loaded with K by administration of 2 mEq KCl/kg/hr through a cerebral (vertebral) artery. K transfer to ICF was calculated and compared with that computed in control animals K-loaded through a PV. At the same rate of K administration, the change of route from PV to VA markedly increased transmembrane K transfer, even in the absence of insulin; the increase seems a specific response to K. KCl administration via a VA, with a resulting abrupt rise in the serum K concentration of cerebral blood, activates a K transfer mechanism (possibly by stimulation of a K-sensitive CNS receptor) that is strikingly unlike the insulin-mediated one stimulated by intravenous KCl. Hyperkalemic dogs may have more than one mechanism for maintaining K homeostasis, depending on the rate at which K enters the circulation.


Effects of ethinyl estradiol on hepatic microsomal proteins and the turnover of cytochrome P-450. The effect of ethinyl estradiol, a steroid commonly used in birth control pills and possibly associated with impaired drug metabolism in humans, on the activity of and turnover of components of the hepatic microsomal mixed-function oxidase system was studied in male rats. After 5 days of ethinyl estradiol, 5 mg/kg/day, there was a significant decrease in the activity of ethylmorphine-N-demethylase and in cytochrome P-450, cytochrome b2, and NADPH cytochrome c reductase. Cytochrome P-450 apoproteins were identified within an SDS-polyacrylamide gel system, and the rate of turnover of cytochrome P-450 apoproteins was studied by double-isotope labeling techniques. After 5 days of ethinyl estradiol administration, the rate of degradation of cytochrome P-450 apoprotein was reduced (half-life of 50 hr compared to 24 hr in control), and their relative rate of synthesis was likewise reduced, indicating that a new steady state of protein turnover associated with reduced synthesis rate had been reached. This was confirmed by studies of the effect of ethinyl estradiol on the level of microsomal cytochrome P-450 over a 10-day period.


Serum urate levels between ages 10 and 14: changes in sex trends. Urate levels were assayed in sera of 292 subjects between 10 and 14 years of age identified through a probability sample of a natural population. The sex trends in serum urate concentrations characteristic of childhood were seen to continue into early adolescence, with girls maintaining slightly higher means. Between 10 and 14 years there was first an overlap of male and female values followed by a reversal of trends, with much higher means in boys. Serum urate concentrations peaked in girls at age 11 and gradually stabilized at lower levels. Boys, on the other hand, showed little age variation in serum urate at 10 and 11 years but by age 12 showed sharp upward trends which continued throughout adolescence. Since age and body weight are known to be important covariates of serum urate, boys were matched to girls of the same age and body weight. Significant sex differences in urate levels persisted (after matching) only for 14-year-old adolescents and thus at this age could not be ascribed to weight differentials. The study highlights a peripubertal phenomenon whose mechanism might be endocrine related.


Retardation in the development of spontaneous hypertension in SH rats by gonadectomy. Young normotensive, male and female rats which develop hypertension spontaneously as they mature were gonadectomized when they were 30 days old. With time, intact controls and sham-operated controls showed a progressive increase in their blood pressure, attaining systolic pressure levels of 180 to 200 mm Hg when they were 120 days old. During this same period, the gonadectomized animals manifested a slight increase in blood pressure without becoming hypertensive. In keeping with their normotensive levels, the gonadectomized rats did not develop any cardiac or renal enlargement. Orchiectomy was associated with retardation of growth, an increase in the ratio of adrenal weight/body weight, concomitant with increased circulating levels of DOC in males vs. reduced DOC levels in females. There was no change in aldosterone levels in either sex. Cmpd. B levels were increased in the gonadectomized males and were slightly reduced in the gonadectomized females. The changes in Cmpd. B, DOC, and aldosterone in these gonadectomized animals cannot account for the inhibition of the spontaneously developing hypertension.


Nasal polyps in cystic fibrosis.

Nasal polyps in cystic fibrosis. In II polyps from patients with cystic fibrosis of the pancreas, the density, shape, and architecture of mucous glands were studied by the whole-mount method and compared with 102 non-cystic-fibrosis polyps. There were no differences in density which was in most polyps less than 0.5 gland/mm.2. The shape and architecture as well as other histological appearances of the polyp were also alike in both groups of polyps which could not be distinguished. The pathogenesis of nasal polyps in cystic fibrosis is discussed. Apparently, it is the same as that of non-cystic-fibrosis polyps.


Nasal polyps, nasal polypectomy, asthma, and aspirin sensitivity. Their association in 445 cases of nasal polyps. In a retrospective study of 445 patients with nasal polyps, 95 (21 per cent) had asthma. Forty-two (44 per cent) of the patients with asthma had been skin tested and 27 (60 per cent) had positive reactions. Nasal polyps were twice as common in men as women, though a woman with nasal polyps was twice as likely to have asthma as a man. The average age of onset of polyps was 39 years and of asthma was 38 years. No significant difference was found in the age of onset of polyps or asthma in various groups of patients. Two per cent of all the patients in the series had nasal polyps, asthma and hypersensitivity to aspirin (the ASA triad). Ten per cent of those with polyps and asthma were hypersensitive to aspirin and thus had the full triad. Overall, 6 per cent of all the patients in the series were recorded as being allergic to aspirin. Asthma developed more commonly before polypectomy than after in the ratio of 2.5:1. Around 1 per cent of first polypectomies and 0.5 per cent of all polypectomies were followed by the development of asthma within a few months. The onset of asthma was found to occur most frequently just before or just after the first polypectomy. Those who developed asthma after polypectomy had significantly more polypectomies than both non-asthmatics and those whose asthma preceded their polyps. Though it is possible polypectomy may on rare occasions precipitate asthma, it is felt that it does not cause it.


The larynx in the cri du chat syndrome.

The larynx in the cri du chat syndrome. The Cri du Chat Syndrome which is caused by a chromosome abnormality is described. A summary of the laryngeal features found by various authors has been made. The characteristic cat-like cry is probably central in origin. The larynx in this condition may be normal or abnormal. If abnormal it is just another clinical manifestation of the syndrome.


A case of aneurysm of the internal jugular vein. A case of swelling of the neck is presented which was clinically diagnosed as an external laryngocele but at operation was found to be an aneurysm of the internal jugular vein.


Iodoform toxicity following the use of B.I.P.P.: a potential hazard. 1. A case of severe iodoform toxicity is presented in a patient after a total maxillectomy whose cavity was packed with B.I.P.P. The patient subsequently recovered after removal of the B.I.P.P. pack. 2. A simple spectrophotometric method for measuring plasma iodine concentration is described. Plasma iodine determinations were carried out on the toxic patient and three others with iodoform containing packs. The concentrations found correspond well with the presence or absence of iodoform toxicity. 3. From the clinical and biochemical evidence presented we suggest that B.I.P.P. gauze is a satisfactory packing for small operative cavities, but that caution should be exercised if large cavities, such as those following maxillectomies, are to be packed with the material. Another iodoform containing mixture, Whitehead's varnish, is a safer alternative to B.I.P.P. gauze.


Intra-articular steroid injection in acute rheumatoid arthritis of the larynx. A case of stridor due to rheumatoid arthritis of the cricoarytenoid joints is presented, with special emphasis on a new line of treatment by local intra-articular steroid injection.


Surface tonsillar microflora versus deep tonsillar microflora in recurrent acute tonsillitis. One hundred patients suffering from recurrent acute tonsillitis were studied. One hundred tonsils were cultured. Surface bacteria were compared to deep bacteria. In 48 per cent of the cases a different pathogen was cultured from the interior of the tonsil as compared to the surface culture. This fact may explain recurrence of tonsillitis and makes the reliability of the conventional tonsillar culture questionable. Surgical extirpation of the tonsils seems to be the only treatment since deep bacteria remain unidentified and resist the antibiotic therapy that may affect only the surface microflora.


Radioimmunoassay of unsulfated lithocholates. A simple, rapid, precise radioimmunoassay for total unsulfate species of lithocholate (lithocholyglycine, lithocholyltaurine, and lithocholate) in serum is described. Antiserum was raised in rabbits by injection of lithocholylglycine coupled to bovine serum albumin (prepared by a carbodiimide method) and emulsified in complete Freund's adjuvant; antisera capable of measuring 40-120 pmol at 1:400 dilution were obtained. The tracer was [11, 12-3[H]lithocholyglycine. The radioimmunoassay featured a 2-hr binding step at 42 decrease C and a 1-hr separation step using polyethylene glycol. The antibody had the following relative specificities: lithocholyglycine and lithocholytaurine, 1; lithocholate, 1.5; chenodeoxycholyglycine, 20; and deoxycholylglycine, 55. There was no binding of various other free or conjugated sulfated and unsulfated bile acids. The mean fasting-state level in 50 healthy subjects was 0.3 mu mol/l (0.14 microgram/ml), but 11 of the 50 subjects had level too low to measure by this technique.


Radioimmunoassay of sulfated lithocholates. A sensitive, rapid radioimmunoassay for sulfated species of lithocholic acid (sulfolithocholyglycine, sulfolithocholyltaurine, and sulfolithocholic acid) was developed and used to measure the total concentration of sulfated lithocholates in serum from healthy human subjects. Sulfolithocholylglycine was conjugated to bovine serum albumin by a carbodiimide procedure, and the reaction product, emulsified in Freund's adjuvant, was injected into rabbits. The antiserum obtained was capable to binding 40% of [3H]sulfolithocholylglycine at 1:1000 dilution. The assay featured a 2-hr binding step at 42 degrees C followed by precipitation of bound tracer with polyethylene glycol at 4 degrees C. The assay can be used with 0.1 ml of serum and was reproducible. The antibody had little affinity for the 3-sulfate of cholic or chenodeoxycholic acid, a number of steroid sulfates, or unsulfated bile acids. In 50 healthy subjects, mean (+/-SE) fasting-state serum levels of immunoreactive sulfated lithocholyl conjugates (+sulfated lithocholate) was 1.6 +/- 0.1 micrometer; based on results with a separate radioimmunoassay for unsulfated lithocholyl conjugates, most of the lithocholate in serum in healthy man is present in sulfated form.


Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats. The aim of the present investigation was to study the influence of cholesterol feeding on cholesterol synthesis and fecal excretion of bile acids in germfree rats. Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 +/- 6.6 (mean +/- SEM) to 9.1 +/- 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and beta-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 +/- 0.2 to 9.9 +/- 1.2 mg/kg body weight per day and beta-muricholic acid from 6.6 +/- 0.5 to 21.8 +/- 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 +/- 1.1 to 31.2 +/- 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of beta-muricholic acid) is stimulated to a greater extent than that of cholic acid.


3-Hydroxy-3-methylglutaryl coenzyme A reductase in isolated villous and crypt cells of the rat ileum. The localization of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34) in the villous and crypt cells of the small intestine was accomplished after separating these cells from the mucosal layer by sequential dissociation in a "dual-buffer" system. Consistent separation was demonstrated by using the marker enzymes alkaline phosphatase, specific to the villous cell, and thymidine kinase, specific to the crypt cell. Cells obtained were 95-100% viable, and no relative difference in lability was observed, as evidenced by the equal distribution of acid phosphatase. This method of cell separation was an improvement over the "scraping" technique which damaged cells severely and produced villous preparations that contained little or no reductase activity. The HMG-CoA reductase specific activity in whole cell homogenates of the ileal villi was 0.47 and of the crypts was 0.27 nmol/min per mg of protein, considerably higher values than have been reported earlier. Also in comparison to the crypts, the villi incorporated 1.5-fold more [(14)C]-acetate into sterols, a ratio similar to that describing the distribution of HMG-CoA reductase in the two cell populations. These results unequivocally establish that the villi have higher HMG-CoA reductase activity than the crypts and confirm an earlier report from this laboratory that the villi are a major site of sterol synthesis. The sterol bio-synthetic capacity of the small intestine was highest in the ileum and decreased towards the jejunum. The HMG-CoA reductase specific activity of the ileum averaged 0.30 and that of the jejunum 0.10 nmol/min per mg of protein; however, the cholesterol content of the ileum was slightly lower than the jejunum. These results are discussed to suggest the possibility that the sterol content of the ileum may largely be due to in situ synthesis.


Puromycin inhibition of cholesterol absorption in the rat. The effect of puromycin on the intestinal absorption of cholesterol has been studied in rats with indwelling catheters in the left thoracic lymphatic duct. Puromycin administration to female rats produced a marked depression of cholesterol absorption under conditions where the absorption of simultaneously administered fatty acid was also dramatically inhibited. The same treatment of male rats also produced a significant depression in cholesterol absorption, but was without effect on absorption of the fatty acid. Despite the depressions of lipid absorption in puromycin-treated animals, there was no accumlation of either cholesterol or fatty acid in the intestinal mucosa of either sex. Actinomycin D treatment of fasting male and female rats, receiving constant infusions of saline, had no effect on the rate of lymph production. This suggest that altered lymph production was not responsible for the depressed lipid absorption observed in fed animals treated with protein synthesis inhibitors. The selective inhibition of cholesterol absorption in male rats also precludes the possibility that the major effect of the inhibitor is on delayed gastric emptying.


Suitability of [11, 12-3H2]chenodeoxycholic acid and [11, 12-3H2]lithocholic acid for isotope dilution studies of bile acid metabolism in man. Studies were carried out to assess the stability of the label in [11,12-(3)H(2)]chenodeoxycholic acid and [11,12-(3)H(2)]lithocholic acid during enterohepatic cycling and thus define the suitability of these tracers for isotope dilution studies of bile acids in man. To do this, [11,12-(3)H(2)]-chenodeoxycholic acid and [24-(14)C]chenodeoxycholic acid were administered simultaneously to six healthy adults. The (3)H/(14)C ratio of biliary chenodeoxycholic acid and the specific activity of biliary chenodeoxycholic acid were determined to permit calculation of pool size and turnover rate by the conventional isotope dilution procedure of Lindstedt (1957. Acta Physiol. Scand. 40: 1). Excretion of label in urine was measured as well as the (3)H/(14)C ratio of fecal bile acids. Similar studies were carried out with [11,12-(3)H(2)]lithocholic acid and [24-(14)C]lithocholic acid. With [11,12-(3)H(2)]chenodeoxycholic acid, 10-15% of the label was lost during the first 24 hours, after which the (3)H/(14)C ratio of biliary chenodeoxycholic acid remained constant. The loss of (3)H caused a consistent overestimate of pool size by 10-15%, but since the fractional turnover rate of the two isotopes was identical, the calculated rate of synthesis was 10-15% greater when determined using (3)H. The loss of (3)H was attributed to the presence of (3)H in positions other than 11 and 12 occurring during the labeling procedure when the unsaturated precursor was exposed to carrier-free tritium gas. The (3)H/(14)C ratio of feces was consistently below that of bile, suggesting bacterial removal of additional (3)H during distal intestinal passage. In contrast, [11,12-(3)H(2)]lithocholic acid lost (3)H continuously, so that by 2 days after administration, the (3)H/(14)C ratio had fallen to nearly half of that of the administered mixture. It is concluded that isotope dilution studies may be carried out with one preparation of [11,12-(3)H(2)]chenodeoxycholic acid with an error of 10-15%; possibly a more stable preparation can be prepared with a gentler tritiation procedure. One preparation of [11,12-(3)H(2)]lithocholic acid was unsatisfactory for isotope dilution studies in man.


Fractionation of human serum lipoproteins by single-spin gradient ultracentrifugation: quantification of apolipoproteins B and A-1 and lipid components. A sensitive and reproducible method has been developed for separation of the major serum lipoproteins from 1 ml or less of human serum by isopycnic density gradient ultracentrifugation. The serum, applied to a step gradient (total volume 12.8 ml), was spun for 48 hr at 38,000 rpm at 10 degrees C and, in each of the fractions, apolipoproteins B and A-I were quantified by the respective radioimmunoassays. The markers for lipid distribution used were [4-(14)C]cholesterol and [U-(14)C]lecithin, each incubated with an aliquot of serum at 20 degrees C for 75 min prior to ultracentrifugation. In control sera, three main fractions, very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins were clearly separated from a bottom fraction. Their flotational, electrophoretic, and chemical properties were in good agreement with those reported for the corresponding lipoproteins separated by conventional ultracentrifugation. Both apo B and apo A-I were fully recovered. Essentially all of the apo B was found in VLDL (9.3 +/- 3.5%) and LDL (87 +/- 4.6%); of the apo A-I, 81.0 +/- 5.7% was in HDL and the remainder (17.0 +/- 5.8%) was in the bottom fraction. The peak activities of [(14)C]cholesterol coincided with the peak of apo B in both LDL and VLDL, and with the peak of apo A-I in HDL. The results with the radiolabeled cholesterol were in good agreement with those obtained by chemical analyses. Carbon 14-labeled lecithin, although fully recovered, was not an accurate marker of phospholipid distribution because, under our experimental conditions, a significant amount of the lecithin was converted into its lyso derivative. The mechanism of the conversion was not established; it appeared to be unrelated to the activities of either lecithin-cholesterol acyl transferase or a Ca(2+)-dependent phospholipase. Besides its validity in the study of control sera, our method also proved successful in the separation of the serum lipoproteins of the few patients with dyslipoproteinemia (abetalipoproteinemia and familial hypercholesterolemia) who were examined. However, the applicability of the method to all dyslipoproteinemias was not assessed. Taken together, the results indicate that the single-spin method could be useful in clinical studies as a complement to other established techniques.


Identification of an adipose tissue-like lipoprotein lipase in perfusates of chicken liver. The nature of the lipolytic activity released from chicken livers perfused with Krebs-Ringer buffer (pH 7.0) containing heparin (50 or 10 U/ml), fraction V albumin (3%), and glycerol (20%) was investigated. The nonrecirculating perfusates contained both previously described NaCl-resistant "liver lipase" as well as an apoLp-Gluactivated lipoprotein lipase (LPL). Crude perfusate lipolytic activity was separated on heparin-Sepharose columns into two enzymatic peaks which were eluted at mean NaCl molarities of 0.75 M (liver lipase) and 1.2 M (LPL). The liver LPL activity was stimulated 7-fold by human apoLp-Glu (half maximal activity at 1.5 microgram/ml) and inhibited by apoLp-Ala, apoLp-Ser, apoLp-GlnI, and apoLP-GlnII. Liver LPL was fully inhibited by anti-adipose LPL immunoglobulins. The "liver lipase" was not affected by apoLp-Glu (3-34 microgram/ml) or anti-adipose LPL immunoglobulins. The data demonstrate the presence in liver perfusates of a LPL with properties similar to adipose tissue lipoprotein lipase.


Storing covariance with nonlinearly interacting neurons. A time-dependent, nonlinear model of neuronal interaction which was probabilistically analyzed in a previous article is shown here to be a natural generalization of the Hartline-Ratliff model of the Limulus retina. Although the primary physical variables in the model are the membrane potentials of neurons, the equations which govern the means and covariances of the membrane potentials are coupled through the average firing rates; as a consequence, the average firing rates control the selective storage and retrieval of covariance information. Motor learning in the cerebellar cortex is treated as a problem of covariance storage, and a predicition is made for the underlying synaptic plasticity: the change in synaptic strength between a parallel fiber and a Purkinje cell should be proportional to the covariance between discharges in the parallel fiber and the climbing fiber. Unlike previous proposals for synaptic plasticity, this prediction requires both facilitation and depression to occur (under different conditions) at the same synapse.


A model for the spatial spread of an epidemic. We set up a deterministic model for the spatial spread of an epidemic. Essentially, the model consists of a nonlinear integral equation which has an unique solution. We show that this solution has a temporally asymptotic limit which describes the final state of the epidemic and is the minimal solution of another nonlinear integral equation. We outline the asymptotic behaviour of this minimal solution at a great distance from the epidemic's origin and generalize D. G. Kendall's pandemic threshold theorem (1957).


Wiener-like system identification in physiology. Applications of Wiener-like identification methods to biological systems have revealed several limitations of this technique. These practical limitations correspond to conceptual and mathematical problems intrinsic to this kind of identification of nonlinear systems.


Photoperiodic control of gonadotrophin secretion in the ram: a detailed study of the temporal changes in plasma levels of follicle-stimulating hormone, luteinizing hormone and testosterone following an abrupt switch from long to short days. Six adult Soay rams were housed under artificial lighting conditions of long days (16 h light:8 h darkness) for 4 months and this caused the animals to lapse into a state of reproductive quiescence with low levels of gonadotrophins in the circulation and regressed testes secreting very low amounts of testosterone. The photoperiod was changed abruptly to short days (8 h light:16 h darkness) to induce a resurgence of sexual activity, and a detailed study was made of the pituitary and testicular responses over the first 100 days. Plasma levels of LH and FSH first began to increase between days 6 and 12 of short days, and rose progressively until days 33-54 before declining again. Testicular growth of the rams began on days 19-26 and continued for most of the remaining period of study. Plasma testosterone levels rose in parallel with the growth of the testes, and were greatly increased by day 100 when gonadotrophin levels were reduced. At most stages there were short-term fluctuations in the plasma levels of FSH, LH and testosterone indicative of episodic secretion. Peaks in plasma levels of LH were especially conspicuous and from the changes in frequency and amplitude of these peaks it was possible to predict the way in which photoperiod influenced gonadotrophin secretion by its effect on hypothalamic LH-RH secretion. A slight 24 h rhythm in the plasma levels of all three hormones was observed, and the significance of this in relation to the photoperiodic response is discussed.


Measurement of free and occupied cytoplasmic and nuclear androgen receptor sites in rat ventral prostate gland. A method has been developed which allows the estimation of occupied and unoccupied androgen receptor sites in both cytoplasmic and nuclear fractions of rat ventral prostate. The procedure involves precipitation of receptor proteins and incubation of precipitates with labelled 5alpha-dihydrotestosterone. Uptake of 3H-labelled steroid at 0--4 degrees C gives an indication of free receptor, whereas binding at a raised temperature (15 degrees C) allows estimation of occupied receptor. Non-specific binding was measured in the presence of a 100-fold excess of unlabelled 5alpha-dilhydrotestosterone. The exchange method was specific for androgens, and specific binding was detected only in fractions of androgen-dependent tissues. The method can be applied to cytosol, whole nuclei, chromatin and salt-extractable and salt-resistant protein preparations from nuclear fractions, and gives a reliable estimate of total receptor sites when occupied as compared with control measurements of unoccupied sites.


Physiological actions of human follicle-stimulating hormone and its beta-subunit in reptiles. The actions of human follicle-stimulating hormone (hFSH) and its beta-subunit were examined in several assays in reptiles, including effects on lizard testicular activity (growth and androgen production) in vivo, and stimulation of androgen production by snake testes and competition for binding of 125I-labeled hFSH in lizards and snakes in vitro. Binding was also examined with mammalian tissues. The hFSH was highly steroidogenic in the snake and lizard; otherwise results were similar to those observed in mammals. In all cases, the potency of the beta-subunit was only a few per cent of the intact hormone. The potency of hFSH in vivo compared with NIH-FSH ovine standards was several 100 times greater than in vitro. Results for stimulation of androgen production in vivo closely paralleled those for binding assays in both reptiles and mammals. In contrast to previous results for ovine FSH beta-subunit, human FSH beta-subunit has little if any FSH biological activity in reptiles.


Immunological studies on parathyroid hormone: characterization of antisera against synthetic 1-34 human parathyroid hormone and evidence that position 30 in human parathyroid hormone is aspartic acid. Radioimmunoassays for the measurement of the 1--34 human parathyroid hormone fragment (1--34 hPTH) were developed using antisera raised in rabbits against synthetic 1--34 hPTH-N (amino acid sequence proposed by Niall). Binding of 125I-labelled 1--34 hPTH-N to these antisera was optimal at pH 5-5. Limits of detection varied between 25 and 200 pg/ml. Cross-reactivity of 1--34 bovine PTH was substantial in all assays; 1--34 hPTH-B (structure proposed by Brewer), 1--84 hPTH and 1--29 hPTH cross-reacted only with antisera from one animal. 1--29 Human PTH was obtained from partial hydrolysis of both 1--84 hPTH and 1--34 hPTH-N. Production of 1--29 hPTH from 1--84 hPTH was demonstrated by comparison of the elution profiles of the reaction product and 1--29 bovine PTH on Sephadex G-50. Thus, evidence was obtained that position 30 in native hPTH is occupied by an aspartic acid residue.


Release of neurophysins I and II during and after parturition in cows. Bovine neurophysin I and neurophysin II (bNpI and bNpII) have been assayed by radioimmunoassay in the jugular venous blood of cows during parturition. In general, low bNpI levels were detected on the day before labour began and during the first stage of labour. Neurophysin I was present in appreciable quantities in blood taken during the second stage of labour and in most cows the concentrations rose to a maximum during the expulsive stage. After delivery, the concentration of bNpI in the blood diminished. This pattern of release is similar to that reported for oxytocin at parturition in cows. As with bNpI, maximum levels of bNpII occurred during the expulsive stage of labour in some animals. In others, bNpII concentrations were very low or absent. Low concentrations of bNpII were found at the other stages of labour. Examination of the results from individual animals indicated that the release of the two neurophysins can be independent.


Venous drainage and functional control of the canine prostate gland. The venous drainage of the canine prostate gland has been studied in nine dogs after post-mortem intravenous injection of a coloured suspension of latex. A submucosal cavernous plexus of the prostatic urethra continuous with that of the penis, and a previously unnamed vessel that drains this plexus into the prostatico-vesical vein are described. The eferential vein was found to open variably, but always into the prostatic venous system. The data support the concept that a very small retrograde blood flow would take androgen-rich blood from the deferential vein into the prostate gland.


Action of rat prolactin on plasma somatomedin levels in the rat and on somatomedin release from perfused rat liver. Rat prolactin at a concentration of 50 ng/ml perfusion medium stimulated the production of somatomedin-like activity (SLA) from the perfused liver of normal rats. The effect was demonstrable in perfusions performed at 11.00 h in which rat prolactin caused a mean (+/- S.E.M.) increase in the uptake of [35S]sulphate into rat costal cartilage in vitro of 64 +/- 14% in comparison with controls, but at 15.00 h no effect was observed. No effect or rat prolactin on hypophysectomized rat liver was detectable at 11.00 h. Hypophysectomized and sham-operated rats were given five intravenous injections of 50 microgram rat prolactin or a similar volume of hormone solvent at 12 h intervals. Plasma somatomedin activity (SMA) and cartilage metabolism, measured by the uptake of radioactive sulphate and thymidine by costal cartilage in vitro, were similar in hypophysectomized animals given rat prolactin or hormone solvent. Sham-operated rats given rat prolactin showed a significant increase of plasma SMA and cartilage metabolism compared with control animals. The production of SLA by rat liver in response to rat prolactin may be related to the density of specific hepatic lactogenic receptors, since these are absent or present only in low numbers in hypophysectomized animals.


The delayed anovulation syndrome: influence of hormones and correlation with behaviour. Experiments were conducted to assess the influence of the ovary and various steroid treatments on the development of the delayed anovulatory syndrome (DAS) in female rats. The influence of neonatally administered androgen on the development of ovarian function and female sexual behaviour was studied. It was found that neither the presence of the ovary nor the administration of oestrogen or androgen affected the time-course of the DAS. Doses of androgen which produced the DAS had little effect on female sexual behaviour and there was no evidence of time-dependent changes in sexual behaviour comparable to the time-dependent changes of ovarian physiology observed during the DAS.


Lactogenic activity in the serum of rabbits during pregnancy and early lactation. The levels of lactogenic activity in the serum of rabbits during pregnancy and early lactation have been determined. The accuracy and sensitivity of the radioreceptor assay used were increased by several technical improvements. Lactogenic activity remained low throughout pregnancy and increased at parturition; the highest values were reached on day 5 of lactation. No lactogenic activity was detected in placental extracts of rabbits, suggesting that the lactogenic activity measured in the serum is solely of pituitary origin. These results are discussed in relation to the main stages of development of rabbit mammary glands.


Changes in steroid concentration in the ovaries of immature rats treated with pregnant mare serum gonadotrophin and human chorionic gonadotrophin. The concentrations of testosterone, progesterone and 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) were measured in the ovaries of immature rats in which ovulation was induced by treatment with pregnant mare serum gonadotrophin (PMSG) and, 48 h later, with human chorionic gonadotrophin (HCG). The concentration of testosterone in the tissue increased significantly 48 h after treatment with PMSG, reached a peak 4 h after the administration of HCG and declined to the basal level 4 h later. Increases in the levels of progesterone and 20alpha-OHP were observed 4 h after the administration of HCG. Whereas the level of 20alpha-OHP continued to rise during the subsequent 30 h, progesterone levels declined near the presumed time of ovulation (12 h after administration of HCG). It is concluded that 20alpha-hydroxysteroid dehydrogenase activity is present in the immature rat ovary before ovulation and that an increase in the production of testosterone in the ovaries of rats treated with PMSG and HCG precedes increased production of progesterone and 20alpha-OHP in these ovaries.


Homologous radioimmunoassay for canine prolactin and its application in various physiological states. The purification of canine prolactin and the development of an homologous radioimmunoassay including several physiological studies in the Beagle dog are described. The assay measured immunoreactive canine prolactin with a sensitivity limit of 0-6 ng/ml. Purified canine luteinizing hormone gave no significant inhibition in the assay whereas purified canine growth hormone inhibited the binding of 125I-labelled canine prolactin to antiserum only at very high dose levels. In Beagle dogs. basal serum prolactin concentrations were in the range 1-2 ng/ml in normal male, normal female (metoestrus and anoestrus) and oophorectomized-hysterectomized female dogs. The prolactin concentration in one sample of amniotic fluid was in the same range, while in hypophysectomized male dogs no serum prolactin could be detected by our assay system. Serum prolactin concentrations tended to increase during late pregnancy and parturition, remaining high during the first 9 days of lactation. In consequence, a negative correlation was suggested between serum prolactin and serum progesterone concentrations.


Suppression of ethanol-reinforced lever pressing by delaying food availability. When food was initially available to rats under a fixed-interval 26-second schedule and each liquid-reinforced lever press delayed food availability 8 seconds, suppression of liquid-reinforced lever pressing and liquid consumption occurred when the liquid presented was 4, 8, 16, 32, and 0% ethanol. Suppression did not occur in yoked-control animals, which received food coincidentally with experimental animals but were not directly exposed to the delay dependency. After exposure to the food schedule, each ethanol solution served as a reinforcer in the absence of food presentation. Delaying food availability for increasingly long periods (8 to 2048 seconds) suppressed ethanol-reinforced lever pressing and consumption relative to baseline levels, with the maximum decrease being below the level maintained in the absence of food. However, degree of suppression did not increase monotonically with delay length. Liquid-reinforced performance of yoked-control animals indicated that suppression did not result from changes in the sequencing of food presentation alone.


Passive transfer of autoimmune disease with isologous IgG1 and IgG2 antibodies to the tubular basement membrane in strain XIII guinea pigs: loss of self-tolerance induced by autoantibodies. Initiation of an autoimmune tubulointerstitial disease was achieved in strain XIII guinea pigs by passive transfer of functionally pure IgG1 or IgG2 fractions of isologous anti-tubular basement membrane (TBM) serum. IgG2 appeared to be somewhat more effective than IgG1. The immunopathologic features in the IgG1 and IgG2 recipients were similar at the time of sacrifice, 14 days after transfer. The recipients that developed disease had higher than expected anti-TBM titers at 14 days. Furthermore, anti-TBM antibodies were of both IgG isotypes. In contrast, simultaneously administered IgG1 or IgG2 anti-BGG antibodies declined in titer in the recipients and were never found in the isotype fraction that had not been transferred. These findings indicate that the recipients of anti-TBM antibodies of either IgG1 or IgG2 isotype were stimulated to produce anti-TBM autoantibodies, which participated in the pathogenesis of the renal disease. The model demonstrates that autoantibodies may provide a mechanism (autoimmune amplification) for the intensification and perpetuation of antibody-mediated autoimmune diseases.


Enzymes of heme metabolism in the kidney: regulation by trace metals which do not form heme complexes. The in vivo regulation by metal ions of the enzymes of heme metabolism in kidney-particularly of ALAS, the rate-limiting enzyme in heine formation- was investigated. Ni(2+) and Pt(4+), metals which do not enzymatically form metalloporphyrins, were found to regulate ALAS in kidney as they do in liver. The pattern of this regulation was generally similar to that observed with heme and metal ions in liver, i.e., a late increase in enzyme activity after an early period in which ALAS activity was unaltered or inhibited. The metals did not interact with the enzyme in vitro to alter its activity. In this study no direct reciprocal relationship between ALAS activity and total cellular heine content was demonstrated. The metal ions, particularly Pt(4+), also altered the activity of other enzymes of heme biosynthesis in kidney. Pt(4+) severely inhibited the activity of ALAD and UROS. Ni(2+) and Pt(4+) were potent inducers of heme oxygenase, the initial and rate-limiting enzyme in heine degradation. It is proposed that the physiological regulation of ALAS is mediated through the action of metal ions, rather than by the cellular content of heine, and that the regulation of ALAS by heine reflects the action of the central metal ion of heme rather than that of the entire metalloporphyrin complex. In this proposed mechanism for metal ion regulation of ALAS, the tetrapyrrole moiety of heine is considered to function principally as an efficient carrier of metal to the regulatory site for ALAS production, inasmuch as the tetrapyrrole ring itself has been shown in earlier studies not to have any effect on ALAS activity. The production of heine oxygenase is believed to be similarly regulated.


Neutralization of reovirus: the gene responsible for the neutralization antigen. The S1 genome segment of reovirus is linked to type specificity as determined by neutralization antibody. This gene segment codes for a minor outer capsid polypeptide (sigma1). Therefore, sigma1 is the peptide responsible for induction of neutralization antibody and confers type specificity. This biologic property of reovirus was defined using hybrid recombinants clones between reovirus types 1 and 3 and 2 and 3.