[Ultrastructure of the cardiomyocytes of the pedicles of the bundle of His in the rat heart]. Light optic and electron microscopic investigation on composition and geometry of His' bundle branching in the upper part of the intraventricular septum was made. Branching of both peduncles of the atrioventricular (AV) bundle were demonstrated to be represented by a single cell type, its ultrastructure was described. Possibility to apply different ultrastructural criteria in order to determine this (III) type of cells in the conducting system of the heart was discussed.


[Architectonics of the capillary bed in the zone of myoneural synapses]. Architectonics of the microcirculatory bed of the motor nerve terminals was studied in the white rat skeletal muscles. The vessels were injected with emulsion of Paris blue combined with impregnation method after Bielschowsky--Gross. Motor nerve terminals were stated to have specialized microvessel bed which ensures hemocirculation and transendothelial metabolism in the zone of their localization. In this zone capillaries form open and closed loops. The open loops, as a rule, are of fork-,horseshoe- and S-like forms. Oval, ring-like and rectangular forms are typical for closed microvessel loops. Interrelations described for the microvessels and the motor nerve terminals determine peculiarities of blood supply in the myoneural synapses at the transition of stimulation from the nerve to the muscle and create certain conditions for adaptation of the terminal sections of microcirculatory bed for changes in metabolic requirements of the myoneural synapses.


[Construction of the microcirculatory bed of the parietal layers of the pleura and peritoneum in newborns]. Structural organization of the microcirculatory bed of the newborn parietal layers in pleura and peritoneum is described as a morphofunctional single whole. Pecularities in the bed construction revealed characterize it as a certain stage in the process of its formation and development. Elucidation of these peculiarities may help to better understanding of disturbances in microcirculatory hemodynamics and tissue metabolism in the newborns and fetuses.


[Nervous apparatus of the 8th pair of cranial nerves after exposure to gravitation loading]. Neural apparatus of epineurium, perineurium and endoneurium of the cat vestibulocochlear nerve was studied by methods of Rasskazova, Bielshowsky--Gross, Kampos, Kuprianov, Gomori, Falck in modification of Chilingarian, Koelle--Gomori, Falck--Hillarp--Govyrin. A single gravitation loading effect was stated to produce reactive, and sometimes destructive changes in the sensitive nervous structures of the intraorganic apparatus of the neural sheaths. The greatest and earliest changes (the first day) were noted in the neural apparatus of epineurium of the vestibulocochlear nerve, the least and latest (the third day) -- in endoneurium.


[Distribution of mineral salts in structures of the compact substance of human bone]. Mineral distribution has been studied in osteoni and intermediate spaces of the compact substance in fibular and occipital human bones. The material has been taken from 34 corpses. Total mineral content was estimated by the contact microroentgenography technique. Calcium, phosphorus and magnium content and distribution were studied by means of X-ray spectral microanalysis. The results obtained characterized bone morphological structure depending on the degree of their miniralization. Peculiarities in calcium and phosphorus distribution along radius osteoni were studied. Quantitative data were obtained on their content in the bone morphological structures. In spite of uneven distribution of some elements in the bone samples, constant molar Ca/P ratio was noted.


[Morphofunctional characteristics of the endocrine cells of the stomach following administration of hydrocortisone and L-thyroxine]. Electron microscopy with application of specific fluorescent histochemical reaction of Falck, as well as some methods of impregnation made it possible to indentify enterochromaffin cells in the stomach of hyperthyroid rats and the rats after cortisone injection under the conditions ox hyperfunction of the thyroid gland. After 20 days of L-thyroxin injection, and after 10 days of hydrocortisone injection, preceded by L-thyroxin, the amount of enterochromaffin cells in the epithelial layer of the gastric mucosa were noted to increase that was accompanied by simultaneous increase of the number of secretory argyrophil granules in their cytoplasm. Simultaneous injection of L-thyroxin and hydrocortisone, while not decreasing statistically significant amount of the cells, produced degradation of their cytoplasm.


[Structural and metabolic disorders in the heart, liver and kidneys in adjuvant disease]. Histochemical changes in the heart, liver and kidneys and ultrastructural disorders in cardiomyocytes were studied in 40 white rats with adjuvant disease. Mucoid lesions, hydropyc dystrophy and necribiosis of muscle cells developed in the heart, diffuse extra-intracapillary glomerulonephritis in combination with nephrosis in the kidneys. In the liver, dyscomplexation of hepatic trabeculas, distention of perisinusoidal spaces were observed; in hepatocytes, the processes of protein synthesis were activated, and signs of hydropyc dystrophy and necrobiosis developed. The activity of enzymes of the aerobic phase of energetic metabolism was reduced and that of lactate dehydrogenase and acid phosphatase increased in cardiomyocytes, hepatocytes, and epithelium of convoluted tubules of the kidneys. Mitochondria of cardiomyocytes were swollen, myofibrilles fragmented.


[Morphologic changes in the nervous system in systemic lupus eryethmatosus]. The central and peripheral nervous systems were examined morphologically in 31 cases of systemic lupus erythematosus (SLE). The lesions of the connective tissue and the vessel walls in the central nervous system are the manifestations of the generalized involvement of the entire connective tissue system in SLE. Morphologic signs relatively specific for SLE, such as fibrinoid necrosis of the connective tissue and vessels, nuclear pathology, as well as myelin changes of pulpous membrnes of nerve fibers and formation of micronecroses in the brain tissue, were observed most frequently in autoimmune crisis conditions. In these cases, a high clinical and immunological activity of the disease was observed.


[Complications of puncture catheterization of the subclavian vein in infants less than 1-year-old]. Autopsies of 61 infants under one year of age with catheterization of subclavian veins revealed in 27 cases complications of catheterization found both isolated and in various combinations. Their nature and frequency differed from those in adults. Noteworthy was a large number of hematomas of anterior mediastinum and parietal thrombi of the right atrium. Severe complications due to the penetration of the catheter into the pleural cavity or to hear perforation were more frequent. Among catheterization complications, emboly of vessels of the greater circulation through patent oval fenestra is possible. The occurrence of severe infectious complications in some cases is associated with the unobservance of the existing contraindications. The high frequency of complications observed at autopsies must be considered in deciding for indications for subclavian vein catheterization in infants under one year of age.


[The thymus in children with brain tumors]. The thymus of 27 children dying with tumors of the central nervous system was studied, most attention being paid to the state of the reticuloepitheilum. Gassal bodies, the presence of pironinophilic cells and lymphoid follicles. The therapy given and the presence of intercurrent infectious diseases were taken into consideration. Morphometry of Gassal bodies followed by statistical treatment of the results was done. The regularity of morphological lesions was found. In the first group of the patients given no specific treatment, the response of the reticuloepithelium to the antigenic stimulation was mostly quite moderate. In the second group where the patients had been operated on and given roentgen and chemotherapy, marked changes in the thymus morphology were observed. In 3 cases of the second group, in addition, lymphoid follicles were found in lobules of the gland.


[Pathologic anatomy of sepsis in children with acute leukemia]. Autopsies of 252 cases of acute leukosis in children dying of sepsis were examined. Except 2, all the children had been in the state of exacerbation of the leukemic process and received current intensive therapy. Sepsis was the immediate cause of death in 68 (26.9%) cases. Most prevalent were such forms of sepsis as sepsis with embolic foci of necrosis in organs (44 cases), septicemia (18), septicopyemia (6). In 40 cases considerable leukemic infiltration of the bone marrow and internal organs, in 18 cases moderate and in 10 poor was observed. The criterian of sepsis in children with acute leukosis is the presence of embolic foci of necrosis, less frequently of metastatic abscesses. All the other signs may be associated both with leukemic and septic processes. The causative agent of sepsis in the majority of cases was hemolytic coagulaso-positive staphylococcus.


[Immunomorphologic criteria of lupoid nephropathy and their value in diagnosing systemic lupus erythematosus]. Immunohistochemical and electron microscopic examinations of 30 kidney bioptates from patients with systemic lupus erythematosus revealed characteristic immunomorphological features of lupoid nephropathy: glomerular immune complexes with the predominance of IgG in combination with other immunoglobulins and fibrin; subendothelial, subepithelial and mesangial depositions in d;fferent combinations found in glomerules; virus-like inclusions in the endothelium of glomerular capillaries. With these signs, the diagnosis of the lupoid nature of nephritis may be established even in those cases where the typical signs of lupus erythematosus are absent or insignificant.


[Light and electron microscopy in determining the histogenesis of vascular tumors]. Six human vascular neoplasms were studied in light and electron microscopes. Electron microscopic examinations revealed specific ultrastructural features of tumour pericytes, cells of smooth-muscle tumours and tumour endothelium. Some tumours were found to be polymorphic in their cellular composition. The electron microscopy method revealed polymorphism of the tumour with diffuse distribution of cell elements (the presence of endothelial strata in hemangiopericytoma or the presence of the pericytic component in an endothelioma) but proved to be of low effectiveness in focal distribution of cell elements. It is concluded from the foregoing that simultaneous utilization of light and electron microscopy is necessary for vertification of such complicated neoplasms as vascular tumours of man.


[Myocardial ultrastructure in fetal rabbits following mechanical trauma]. An area of the myocardium of 23-day-old rabbit fetuses after mechanical tramua was studied electron-microscopically. Six days after trauma in the focus of lesion myocardial cells were found the general submicroscopic organization of which was identical to the ultrastructure of myocardium cells of intact animals and muscle cells of other parts of the left ventricle of the heart of experimental animals. Besides, in the former focus of lesion of the myocardium tissue electron microscopy revealed younger myocardial cells than those in the myocardium of the intact animals as well as cells showing early stages of differentiation. The results indicate that at the site of the lost myocardial tissue in 23-day-old rabbit fetuses 6 days after trauma there appears an intact cross-striated musculature of the heart.


[Postmortem changes in skin color].

[Postmortem changes in skin color]. By the employment of the colorimetric method statistically significant objective data on postmortem changes in the colour of different parts of the skin have first been obtained. Histological and spectrophotometric studies were carried out in order to elucidate the causes of these changes. The colour of the cadavar skin as well as the colour of the human skin in life depends on primary pigments: hemoglobin, melanin, carotene and melanoid. A certain role is likely to be played by the main structural proteins of the derma and epidermis: collagen and keratin. The cadavar skin colour differs in variations of the dominant wave length and reflectance which are associated with postmortem redistribution of the blood under the effect of the gravity and qualitative transformation of oxyhaemoglobin into reduced haemoglobin. The distribution of melanin, carotene, and melanoid does not differ from that in life. The most specific index of the amount of melanin is the purity of colour and not reflectance.


[Corticosteroma and gangliocytic neurilemmoma of the left adrenal associated with diffuse nodular hyperplasia and gangliocytoma of the right adrenal]. In a man of 48 who had suffered for a long time from a high arterial blood pressure, the autopsy revealed corticosteroma of the left and diffuse-nodular hyperplasia of the right adrenal glands. Both adrenals also had tumours of the sympathetic nervous system considered to be a gangliocytoneurilemmoma (angliocytic neurilemmoma) on the left and gangliocytoma on the right. The combination of morphological lesions, clinical data and laboratory examinations permit to state a combination of hypercorticism and hypercatecholaminemia.


[The operative treatment of the spondylolisthesis with compression screws (author's transl)]. The author gives account of a direct osteosynthesis--joining the defect of the interarticular part--made in case of spondylolisthesis in his department. They carry out the operation having modified the method of Buck as they use A-O malleolar compression screw instead of all threaded screw. Applying compression screws the author can ensure a successful osteosynthesis in case of a greater vertebral displacement. This method widens the indication area of the operation. The adventage of the operation over other ones made in spondylolisthesis is the fact that after the wound-healing the patient can get up and the lumbar spine will not be limited in motion. The operation was made in 16 cases until now and operative complication was not observed. They propose to make this operation as early as possible in case of definite spondylolisthesis to prevent the development of further progression.


[Minimal internal fixation of fractures in elder children (author's transl)]. The fractures in elder children (9--17 years) need a special treatment. Regarding the exact reposition they have to be handled like the fractures of adults. Regarding localisation, morphology of the bone and the way of internal fixation they have to be treated like those of smaller children. The "Minimal-Osteosynthesis" primarily means adaptation, refixation and continuous retention. The procedure is less traumatizing, however the indication should be as strictly as in other cases. The minimal osteosynthesis is giving more respect to the growing bone. The material of internal fixation may be removed much earlier than in adults. Stability for early physical exercises is rarely necessary in children. Even different types of minimal internal fixation are possible. A number of cases are demonstrated.


[The extension nail. A new method for lengthening of the femur and tibia (author's transl)]. The paper introduces a new method for limb lengthening using an extension nail. Animal and clinical results are encouraging. Further clinical results and long term observations will be presented soon.


[Complete resection of a vertebral body (author's transl)]. The resection of one or more vertebral bodies is technically difficult and quite demanding for the patient. In cases of solitary metastases to a vertebral body such a procedure may be considered when the general condition of the patient is satisfactory. To mobilise the patient quickly the stabilisation of the spine with bone cement and plates is mandatory. Three of four cases have been treated by two consecutive operations, one patient received a prefabricated ceramic implant. Mobilisation was maintained until four months after surgery. An analysis of previously published reports on complete vertebral body resection shows advantages and disadvantages of several methods.


[Post-operative surveillance and intensive care after orthopedic procedures of the vertebral column (author's transl)]. 113 corrective procedures of the vertebral column by ventral and/or dorsal approach have been analysed. The post-operative findings have been reported, including blood-gas analysis, hemoglobin and hematocrit, electrolytes, and fluid balance. A correlative-statistical analysis of the scoliosis group was carried out according to number of involved segments, degree of curvature, age, length of operative time and total blood loss. The post-operative complications were related to preexisting risk factors.


[Fractures of the neck of femur in juveniles (author's transl)]. The problems of the treatment of femoral neck fractures in young patients are discussed on 22 cases as well as the operative technique, post-operative treatment, late complications and their treatment. We feel that femoral neck fractures in children and young ones should be treated operatively. The three flanged nail should be used for internal fixation, giving a better fixation than K-wires. We have not seen any damage caused by the crossing of the epiphyseal plate with a nail or K-wires. Postoperatively the patient should walk non weight bearing on the fractured hip for 9 months, especially in transcervical fractures. The danger of aseptic necrosis of the femoral head is clearly diminished by this precaution. The late results of femoral neck fractures in juveniles are clearly worse than in children. The femoral neck fracture of the young is to be treated as an emergency. If the therapy is too late or not adequate the consequences for the hip joints of the juveniles can be drastic.


[Pelvic fractures in children: clinic, late results, biomechanic (author's transl)]. From 1917--1976 68 pelvis fractures of children (up to 14 years) were hospitalized at the department of Surgery, University of Göttingen. About 75% were traffic accidents. The lesions prefer the iliosacral joints, symphysis and the biogenic connections. Experimental compressions confirm the clinical fractures. The controls show sufficient subjective results. Because of pelvis dislocation and scoliosis controls are necessary.


[Corrective osteotomy for malalignment of fractures of the distal radius (author's transl)]. Corrective osteotomy is indicated in young manual workers with significant malalignment after fracture of the distal radius without associated degenerative changes in the wrist joint. Chronic pain, limited motion and impaired power can be avoided and the cosmetic appearance of the hand improved, by restoration of the functional anatomy of the wrist. The operation consists of an opening-wedge osteotomy at the fracture site, sometimes combined with resection of the distal ulna. The approach may be dorsal or volar. A small iliac cortico-cancellous bone graft is inserted at the osteotomy site. Fixation is by an AO-small fragment-T-plate allowing early functional after-treatment.


[Immunological aspects of syngenesioplastic bone transplantation in treatment of infantile bone tumors (author's transl)]. Bone transplantations are made often in the treatment of benign bone tumours or tumour like affections. Especially at the appropriate infantile illness the use of an autologous transplant may prove impossible. Homologous and heterologous osseous transplants are largely unsuitable, because of the induction of immunological reactions. So called syngenesioplastic transplants let expect a tolerance of the recipient organism. This is a report of the results of clinical, radiological and especially immunological follow-up-examinations of 11 patients treated from August 1974 to October 1976 with syngenesioplastic spongiosa transplantation.


Hydatid disease in Australia.

Hydatid disease in Australia. Human hydatidosis is caused by infection with the cystic stage of the hydatid tapeworm of dogs, Echinococcus granulosus. Although the disease is entirely preventable, the prevalence of hydatidosis in Australia has not decreased since the first surveys were taken in the early part of this century. Principal reasons for this appear to be a general lack of knowledge of the life history, epidemiology and control methods for E. granulosus, coupled with ineffective community based eradication campaigns. The purpose of this paper is to briefly discuss the important facts relevant to control and eventual eradication of hydatid disease.


Toxocariasis.

Toxocariasis. Human infection with the larvae of the dog roundworm, Toxocara canis, occurs in Australia, especially in children, and though usually not serious, it can cause considerable damage if the larvae get into such organs as the eye.


Hazards of domestic pets. Ringworm and other skin conditions. Domestic pets may be responsible for a number of skin eruptions in man. Whilst ringworm due to Microsporum canis is one of the most common of these conditions in this country, trichophyton infection, flea bite dermatitis, cheyletiella dermatitis, canine scabies and traumatic dermatitis are by no means rare. Less frequently encountered conditions include creeping eruption, favus, fowl-mite dermatitis and allergic dermatitis.


Toxoplasmosis.

Toxoplasmosis. Recent research has shown that Toxoplasma gondii, the cause of human toxoplasmosis, is a protozoan close to the genus Isospora, whose life cycle involves cats as the definitive host, and other mammals, including man, and birds as intermediate hosts. Cats shed oocysts in their faeces; these are infective to the intermediate hosts when ingested. But the non-felid intermediate hosts can also become infected by eating other intermediate hosts. Probably most human infections occur in this manner and result from eating raw or insufficiently cooked meats. Most people become infected during their life time, but most infections are benign and unnoticed. Occasionally the disease picture may simulate infectious mononucleosis. However, in intrauterine or neonatal infections the disease may be most severe and chorioretinitis, encephalomyelitis, hydrocephalus or microcephaly may result. Diagnosis depends upon demonstrating the parasite in biopsy material or through changing titres in serological tests.


Behaviour therapy for psychosexual dysfunction. Behaviour therapy is defined, and the therapeutic approach evolved by Masters and Johnson described. Their key concept of the desirability of treating couples and using co-therapists is evaluated in the light of research findings. It would seem that co-therapy is desirable, but a single therapist can do useful work with a single patient, a couple, or a group of couples using a behaviour therapy framework. Two illustrative cases are described.


Medical problems of the overland route from India or South Africa to Europe. The various problems of the overland traveller are discussed, as are the necessary immunization procedures, the seriousness of falciparum malaria and the various bowel disorders. The necessity for treating minor injuries and abrasions is stressed. Psychological problems, veneral disease and the problem of drug abuse are mentioned.


The diagnosis and management of acute viral hepatitis. While there is a declining incidence of many infectious diseases, viral hepatitis persists as a major problem. In fact, there would appear to be an increasing incidence of hepatitis B paralleling the rising problem of drug addiction. The discovery of Australia antigen, now called hepatitis B surface antigen (HBsAG), represented a major breakthrough in our understanding of viral hepatitis. More recently, serological tests have become available for hepatitis A virus (HAV) which will further facilitate our understanding of acute and chronic hepatitis.


Isolation of toxic metabolites of Phomopsis leptostromiformis responsible for lupinosis. Two metabolites of P. leptostromiformis (phomopsins A and B) have been isolated as a crystalline mixture from a culture of the fungus on lupin seed. The mixture has been shown to be capable of inducing lupinosis in sheep and in young rats. Key steps in the isolation were the transfer of the phomopsins from crude aqueous solution to tetrahydrofuran and chromatography on macroreticular polystyrene resin. The bioassays used in monitoring fractions were based on inhibition of cell cultures and the mitosis-arresting effect of the metabolites on liver cells in vivo.


Plasma progesterone, FSH and LH levels associated with implantation in the mouse. Measurement of plasma progesterone, LH and FSH were made every 6 h during the first 6 days of pregnancy in the mouse. Plasma progesterone and LH were low on day 1, minimum values being recorded at 24 h post coitus. Concentrations of both these hormones started rising during the second half on day 2 with the rise continuing during day 3 to a progesterone peak of 25 ng/ml early on day 4 and an LH peak of 37 ng/ml late on day 4. Levels of progesterone fell during day 4 and LH during day 5 to approximately half their respective peak values and then remained relatively constant over the remainder of the measurement period. Levels of FSH, which were high early on day 1 (180 ng/ml), fell sharply by midday with a small rise late in the day followed by a decline during day 2 to a minimum level of 2 ng/ml at 48 h post coitus. Early on day 3 FSH values rose to 120 ng/ml then fell to 50-60 ng/ml during the next 6 h and remained relatively stable at this level during days 4 and 5. It is suggested that LH is concerned with progesterone production and maintenance of the corpus luteum whilst FSH is concerned with the production of oestrogen required for implantation in this species.


Effects of low concentrations of cetyltrimethylammonium bromide on diluted bovine spermatozoa. Cetyltrimethylammonium bromide (CTAB) at a concentration of 10 mg/l in a citrate buffer partially protected sperm against the effects of cold shock treatment. CTAB concentrations of 10 and 20 mg/l also increased in vitro sperm livability when semen was diluted in Caprogen and incubated at 37 degrees C (50 h v. 60 and 57 h). Concentrations of CTAB exceeding 50 mg/l reduced in vitro sperm livability. The addition of catalase (4.5 mg/l) to Caprogen produced greater increases in in vitro sperm livability (50 h v. 110 h), but did not eliminate the toxic effect of the higher CTAB concentrations. The addition of CTAB (10 mg/l) to the Caprogen-catalase diluent significantly increased the non-return rate of the diluted semen in only one of four large-scale field trials and did not alter non-return rates with deep-frozen semen.


A comparative study of the NAH and TOL catabolic plasmids in Pseudomonas putida. A comparative study of the NAH and TOL catabolic plasmids was carried out to provide information for future genetic manipulation experiments involving these two plasmids. The plasmids were studied in a strain of P. putida and its mutant derivatives. The NAH and TOL plasmids were found to be incompatible. Under the conditions used in these experiments the TOL plasmid transferred into some strains into which NAH was unable to transfer. The use of mutants to remove certain catabolic activities encoded by the bacterial host cell facilitated the allocation of growth genotypes to the NAH and TOL plasmids. TOL encoded the degradation of benzoate, m-toluate and p-toluate, whereas NAH encoded the degradation of naphthalene and salicylate. The other plasmid-associated growth phenotypes were partly plasmid-specified and partly specified by the host cell. The pH optimum of the catechol 2,3-dioxygenase specified by the TOL plasmid was approximately 6.7, whereas that of the NAH-encoded enzyme was approximately 8.3.


Incorporation of [2-3H] ethanolamine into rat muscle phosphoglycerides. The contribution of phosphatidylethanolamine methylation to phosphatidylcholine biosynthesis in rat muscle was investigated by studying the incorporation of [2-3H] ethanolamine. The specific radioactivities of individual molecular species of muscle phosphoglycerides were measured by a combination of argentation thin-layer chromatography and countercurrent distribution. The specific radioactivity of phosphatidylethanolamine was approximately one thousand times that of phosphatidylcholine. Amongst individual phosphatidylethanolamines, hexaenoic species possessed the highest specific radioactivities and tetraenoic the lowest. Because of the very low incorporation into phosphatidylcholine, the specific radioactivities of combined rather than of individual fractions were measured. The results indicate that the contribution of phosphatidylethanolamine methylation to the overall biosynthesis of phosphatidylcholine in muscle is of minor importance.


Re-examination of small intestinal disposal of Vibrio cholerae in mice. The rapid disposal of antibody-treated vibrios by peristalsis in whole animal models makes it difficult to obtain clear evidence for a simultaneous intra-intestinal bactericidal effect. In this paper we have re-examined the evidence for direct intra-intestinal killing. We have found that the data can be explained adequately by peristaltic effects without postulating a direct bactericidal action in vivo.


Induction of immunity in mice to the nematode parasite, Nematospiroides dubius. The data presented in this paper show that mice may be immunised against re-infection with Nematospiroides dubius by giving live third-stage larvae orally, intravenously, intraperitoneally or subcutaneously. Immunity is directed not against the adult worm but against third-stage larvae following their penetration of the wall of the intestine.


Effect of enteric micro-organisms on intestinal sugar and fatty acid absorption. The effect of micro-organisms contaminating the upper intestinal contents of malnourished children on intestinal absorption of 3-0 methyl-alpha-D-glucopyranose (3-M.G.) and oleic acid was studied in rats in vivo. Oleci acid absorption was unaffected by non-pathogenic E. coli but decreased by E. coli 0111, Salmonella paratyphi B., Shigella sonnei and Candida sp. This effect was probably explained by intestinal secretion diluting the test solution leading to a decreased diffusion gradient for solubilised fatty acid. Inhibition of sugar absorption occurred with bacterial suspensions of Staphylococcus aureus, Streptococcus faecalis, E. coli and Candida sp. and cell-free preparations of Staphylococcus aureus, Streptococcus faecalis, a non-pathogenic E. coli, Proteus sp., Klebsiella sp., Pseudomonas sp. and Candida sp. These effects were not explained by dilution of the test solution. This indicates that numerous micro-organisms and, in some instances, their cell-free preparations can interfere with intestinal active sugar transport. These findings may be relevant to the production of malabsorption in malnourished children who have a wide variety of micro-organisms contaminating their upper intestinal contents.


The metabolism of exogenous histamine by aortic tissues. A thin layer chromatographic system is presented for the separation of histamine (H), 1,4-methylhistamine (M), acid metabolites comprising imidazole and methylimidazole acetic acids (A) and N-acetylhistamine (N). The system was applied to separation of the histamine metabolites formed following incubation of rabbit and guinea-pig thoracic aorta segments with labelled histamine. The effects of various agents known to affect histamine uptake, storage and metabolism in vascular tissue were studied on the disposition of histamine metabolites.


The origin of the muscle fasciculation caused by funnel-web spider venom. The origin of the fasciculation of skeletal muscle produced by funnel-web spider venom (FSV) has been examined in mouse phrenic nerve hemi-diaphragm preparations, FSV from male spiders at concentrations greater than 10(-6) g/ ml invariably produced muscle fasciculation which could be prevented by d-tubocurarine (14micron), tetrodotoxin (0.3 micron) or by increasing the external magnesium concentration or calcium concentration. Diphenyl hydantoin (3-6 X 10(-5) M) was able to reduce these fasciculations in some experiments. In curarized preparations, multiple end plate potentials (EPPs) in response to single stimuli and bursts of spontaneous EPPs were seen in the presence of FSV (10(-5) g/ml). Extracellular recordings from phrenic nerves in the presence of FSV (10(-5) g/ml) revealed additional components in compound action potentials elicited by single stimuli, and "spontaneous" electrical activity was observed in unstimulated nerves. This spontaneous activity was abolished by raising the divalent cation concentration in the bathing solution. These results suggest that a primary site of action of FSV is the surface membrane of nerve fibres and that muscle fasciculation arises as a consequence of spontaneous action potentials produced by the venom in motor nerves.


Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): oxygen consumption and temperature regulation. In keeping with studies of other desert rodents, the potentially diabetic spiny mouse has been demonstrated to have a very low basal metabolic rate, disproportionate to its body weight. The maintenance of a lower body temperature in response to high environmental temperatures and a lack of increase in metabolic rate in response to cooling have also been demonstrated. Assessments of "mechanical efficiency" have shown that spiny mice carry a potential selective advantage under fasting conditions. The findings, some of which are similar to those noted in other desert rodents, and in other species showing either spontaneous or induced hyperglycaemia, suggest that the low metabolic rate is at least partly based on ineffective glucose utilization. This phenomenon may be the common denominator of the survival advantage which has allowed both the successful evolution of species inhabiting warm, arid climes, and the persistence of the diabetic genotype in animal and human populations.


Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): cold tolerance: blood glucose and food consumption responses to environmental heat. Decreased cold tolerance, reduced food requirement for body weight maintenance and comparative resistance to the hypoglycaemic effect of fasting in high ambient temperatures have been demonstrated in the spiny mouse. These phenomena could be related to anomalous spiny mouse thermoregulation, a phenomenon which is common in desert rodents and is simulated by mutant and artificially diabetic rodent species. The data can be interpreted as showing evidence for a survival advantage of genotypes with potential diabetic expression, and may provide an explanation of the geographic distribution of certain species.


Studies on immune responses to larval cestodes in mice: a simple mechanism of non-specific immunosuppression in Mesocestoides corti-infected mice. After intraperitoneal (i.p.) injection of sheep erythrocytes (SRBC) or dinitrophenylated Ficoll (DNP-Ficoll), mice infected with the larval cestode, Mesocestoides corti, contain at least 20x fewer antibody-secreting cells (PFC) in their spleens (or spleens plus lymph nodes) than uninfected mice. By contrast, intravenous injection of antigen leads to normal PFC responses. Results of studies on the fate of labelled syngeneic erythrocytes and foreign proteins suggest that i.p. injected materials are retained in the inflamed peritoneal cavity. Sequestration of antigen, and its subsequent local destruction, presumably accounts for the markedly suppressed systemic immune responses induced by i.p. injected antigens in M. corti-infected mice.


Preabsorptive vs. postabsorptive control of ethanol intake in C57BL/6J and DBA/2J mice. Experimentally naive male mice of both strains were exposed to a two-bottle choice situation (ethanol vs. water) and their drinking behavior was observed during the first hour. DBA/2J mice developed a significant avoidance of 2% or 10% ethanol during the first 10 min. At 15 and 60 min following introduction of the bottles, no DBA mouse exhibited more than a 6 mg% blood ethanol level while all of the C57BL mice exceeded this concentration. Significant postabsorptive effects in the DBA mice seem unlikely at these very low blood ethanol values. Animals of both strains were examined for their ability to form lithium-induced conditioned taste aversions to 2% ethanol or 15% sucrose solutions. DBA mice readily formed conditioned aversions to both solutions, but the C57BL strain significantly avoided only the sucrose. C57BL mice appear to have difficulty in discriminating the 2% ethanol from distilled water. The neural sensitivity to ethanol was examined in both strains using the sleep time test and the grid test. C57BL mice were significantly more sensitive than DBA mice in both tests.


A test for rare male mating advantage at an "enzyme locus" in Drosophila. Matings between Drosophila pseudoobscura strains differing at the amylase (Amy) locus were observed in Elens-Wattiaux chambers. Males homozygous for either Amy1.00 or Amy0.84 alleles in the CH gene arrangement enjoyed a mating advantage when moderately rare, but none when quite rare. The minority male advantage for strains differing at the Amy locus, and other loci linked to it, was comparable in size to that observed between strains carrying the ST or CH gene arrangements, and either alike or different at the Amy locus. Although some features of our results are puzzling, there is evidence that the Amy locus and others for which it serves as a marker have effects on mating behavior which include some degree of rare male mating advantage.


Open-field behavior in mice: generality of results from a diallel analysis of replicate selected lines. Data from a diallel cross of six lines composing a replicated selection study for open-field behavior in mice are reanalyzed to investigate the generality of the findings. The results support the hypothesis that only additive variation would be found for open-field behavior if additional selection lines were derived from the same foundation population.


The aptitude-achievement test distinction: a study of unrelated children reared together. Unrelated children reared together (N = 156) in 71 different families included in the Texas Adoption Project were compared for similarities on intelligence and achievement tests. The purpose was to see if a distinction between the two types of tests based on their heritabilities could be sustained. Results indicated no substantial differences in correlations for the two types of tests, and hence little or no support for the notion of an aptitude-achievement distinction based on differential heritabilities.


Studies on the pathogenesis of ischemic cell injury. VII. Proton gradient and respiration of renal tissue cubes, renal mitochondrial and submitochondrial particles following ischemic cell injury. Electron transport in tissue cubes, isolated mitochondria and submitochondria particles were examined as a function of ischemic time. It was found that electron transport remains active in all systems beyond the 2 hour ischemic time interval. The NADH stimulated respiration, however, declined after 2 hours of ischemia in ASU (Ammonia-Sephadex-Urea) particles followed by respiration with matrix-located dehydrogenases tested by substrates such as glutamate, alpha-ketoglutarate and pyruvate plus malate. Succinate dependent respiration remains active at control levels. In contrast proton gradient reveals changes in two phases: Phase A is characterized by gradually increasing gradient without valinomycin and by a rapidly declining gradient with valinomycin in the medium. Phase B is characterized by a declining proton gradient with or without valinomycin. It is suggested that the alteration of the proton gradient between 1 and 2 hours ischemia is an important factor contributing to irreversible cell injury.


Postmortem changes in stereological parameters of cerebral capillaries. The present study investigated the influence of different postmortem times on stereological parameters of capillaries in the cerebral cortex. For the human investigation different brain regions of two 77 and 79 year-old subjects were examined. The animal experiment, carried out on 10 male cats, allowed a comparison between intravitam deep-frozen cerebral cortex and tissue obtained after decapitation. The parameters were diameter Di, volume fraction VVi, surface-to-volume ratio Si/Vi, mean minimal distance between capillary centers of gravity deltaAB, length per unit cortex volume LVi, and number of fragments per measuring field Ni, AT. Neither the cat experiment nor the human investigation yielded a noteworthy change of the capillary diameter in the postmortem cortical tissue. Nevertheless, a significantly enlarged mean minimal distance between capillaries in the cat cerebral cortex shortly after decapitation (30 sec) suggests the formation of edema which then regresses. Furthermore the experiment revealed that 22 hours after death there is a significantly (p less than 0.01) diminished volume fraction and length per unit cortex volume with an augmented surface-to-volume ratio. These changes are thought to be a consequence of water loss. In contrast to the animal experiment the human cerebral capillaries showed no changes in stereological parameters at two different postmortem times. These results encourage continuation of further stereological investigations on human brains obtained at autopsy and may contribute to the understanding of the aging process in the human cerebral cortex.


[Extremly high frequency of infantil pulmonary thrombo-embolism (author's transl)]. Among 5 875 children with a lifetime between 24 hours to 14 years, autopsiated during period 1951-1970, were found 115 cases of naked eye pulmonary thrombo-embolism. 96 cases occurred in children with a lifetime between 24 hours and 4 years. This extremly high frequency is caused by an unusually high number of thrombosis in renal veins and craneal sinuses, following severe diarrhetic diseases with deshydratation and haemoconcentration. Severity and frequency of this enterocolitis of different aetiology, affecting especially children of poor people, are favoured by the climatic, sanitarious and socio-economical conditions of Valencia. Surprisingly, literature do not mention comparables observations about infantil pulmonary thrombo-embolism, observed in territories of similar structure.


[Studies of climatic factors influencing the performance of cattle in the Syrian Arab Republic. 3. Assessment of the factors effective in 1969/70--comparison with those of 1968/69]. Continuing previous investigations (1968/69), the values of temperature and humidity (inside and outside the cowsheds) were determined for the period October 1969 to September 1970. They were related to the physiological compatibility ranges established for dairy cattle and discussed in connection with a cowshed scheme in the Animal Experimental Station at Deir el Hajar in the Syrian Arab Republic. The values obtained in the two years of investigation largely agreed. The means of the temperature in both years was 27.7% inside and 30.5% outside the cowsheds above the physiologically compatible range of 0 to 24 degrees C for the whole period. Only in 47.6% and 46.7%, respectively, of the overall hours the temperature inside and outside the cowsheds was within the optimum compatibility range for dairy cattle. 43.5% of the relative humidity outside the cowshed was in the too dry and 21.7% was in the too moist compatibility range.


A comparison of the effect of oleandomycin and oxytetracycline supplementation on the growth and the meat quality of Dokki-4 chicks reared in hot weather. 1000 chickens were used to investigate up to 24 weeks under high environmental temperatures the addition of different types (oxytetracycline and oleandomycin) and different levels (5 or 20 ppm) of antibiotics to the basal diet. Supplementation with 20 ppm had--with both types of antibiotics--a marked positive effect on the growth rate and various quality characteristics of the products. The effect was higher in male animals than in females.


In vivo microscopy of the spleen.

In vivo microscopy of the spleen. The use of improved in vivo microscopic methods has permitted a reevaluation of the "open" vs. "closed" theory of blood flow through the splenic red pulp. The microscopic methods used for studying the spleen in vivo are described as are the results, both of which were presented in motion picture form at this symposium. The results strongly suggest that, in general, there is little or no continuity of endothelium through the splenic red pulp. Instead, blood flows from "arterial" capillaries lined with endothelium into channels within the red pulp formed by the cytoplasmic processes of reticular cells. In vivo these processes appear similar to endothelium. Blood leaves the red pulp by passing through apertures in the endothelium of sinuses and venules.


Oxygen tension in different tissues.

Oxygen tension in different tissues. Our findings of studies in critically ill patients can be summarized as follows: 1) Adequacy of tissue oxygenation cannot be predicted solely from measurement of arterial blood Po2 since normal values may be associated with an inadequate tissue oxygen supply. 2) Measurements of global blood flow are in no way indicative of the distribution of blood flow within an organ and point to need for more specific monitoring within organs of both low distribution and metabolic activity.


The influence of hemodynamics upon platelet adhesion to collagen-coated surfaces. These results indicate that hematocrit and surface shear rate must be considered in determination of the rate of transport, limiting transport step and surface saturation condition. Low hematocrit and shear rate lead to a slow rate and low saturation; high hematocrit and shear rate lead to fast rate and high saturation. Surface reaction rather than diffusional transport controls the adhesion process at low hematocrit. Platelet thrombi, however, may not be favored by high shear conditions due to increased transport from the surface of released aggregate forming substances.


Edema in cerebrovascular disease.

Edema in cerebrovascular disease. To date a few clinical methods give a certain hint as to the presence of brain edema and even its most probable localization; only one method, the recently developed computer tomography can be regarded as fairly reliable. However, as long as the pathogenesis of brain edema is not yet sufficiently elucidated and therapeutic methods are not developed either to prevent or remove intra-or extra-cellular edema distinctly and separately in experimental lesions, the lack of adequate technology for a refined diagnosis in the human is not urgent.


Muscle capillaries and retinopathy among Israeli diabetics. With special reference to measurement techniques, relationship to age and the pericyte. Our investigation of the capillaries of 64 Israeli diabetics confirm the fact that retinopathy is consistently associated with thickening of the basal lamina of peripheral muscle capillaries but the converse is not so. The change in pericapillary structure may affect the capillary function. The primary cell involved, either causally or as a consequence of the lexion, is the pericyte.


Intraocular pressure and diabetic retinopathy. Between intraocular pressure (I.O.P.) and the metabolic carbohydrate disturbance is a relationship: 1. diabetics frequently show primary open angle-galucoma; 2. as the diabetic retinopathy progresses towards stage III (Pr.), IOP decreases; 3. as diabetics exhibit dilatation of veins, increased blood viscosity, arteriolar narrowing and increased I.O.P. central retinal vessel disease with hemorrhages occurs redily; 4. capillary hemorrhages, periapaillary and macular oedema may be caused by increased oncotic pressure with acidosis of the blood; hyperglycemia with ketosis goes together with decreased I.O.P.; 5. only mild I.O.P.-rise may be considered as usefull to prevent hemorrhages by reducing retinal blood flow resulting subsequently from reduced uveal blood flow; 6. local application of glucocorticoids with permanent control of visual fields and I.O.P. should be a good additional treatment for diabetic retinopathy; unfortunately only very few cases are responsive to increase of I.O.P. by glucocorticoids; 7. it is important that prolactine levels in the blood are higher in the morning before the patient wakes up: this goes together with the morning I.O.P.-rise in glaucoma patients. Decreased activity of the hypophysis improves the diabetic retinopathy; this is contradictory to the beneficial effect of mild I.O.P.-rise.


Investigation of conjunctival vessels in diabetics with and without retinopathy by means of a microcirculation-index. We were unable to trace an unmistakable correlation between changes on the fundus of the eye and changes on the conjunctiva neither by taking the sum of single findings at the bulbar conjunctiva nor by using a respective index. I.e. the findings of the bulbar conjunctiva are not correlative neither to the stages of diabetic retinopathy nor the duration of diabetes. Clinical experiences make us suppose that the vessels of the fundus of the eye are closely connected to the circulation of the cerebral flow whereas the changes of the conjunctival vascular bed may possibly correlate in a better way with the peripheral vessels. The present results show that the majority of the patients with a high index at the bulbar conjunctiva suffer from peripheral occlusive disease.


Clinical rheology in cardiovascular disease. A protocol has been designed to evaluate the role of each of 4 determinants of blood viscosity. Studies on cardiovascular diseases showed that abnormal blood rheology may play a role in hemodynamic derangements. Investigations on clinical rheology not only help to elucidate the pathophysiological basis of the disease process, but also serve to improve our understanding of the fundamental mechanisms of regulation of blood viscosity.


Adrenergic activity and intraocular pressure. Systemically-administered noradrenaline lowers intraocular pressure; isoproterenol, similarly administered, has an intraocular pressure-raising effect. Unless extremely low doses are used, these effects will be marked by opposite changes in arterial perfusing pressure. Intraocular pressure-regulating mechanisms carry both alpha- and beta-receptors. Stimulation of alpha-receptors decreases intraocular pressure, while stimulation of beta-receptors increases intraocular pressure. Intraocular pressure is under tonic sympathetic influence.


Breakdown of the blood: aqueous barrier and prostaglandins. The quantitative relationship between the degree of breakdown of the blood-aqueous barrier and aqueous humor prostaglandin content was studied in rabbits. After the primary aspiration of the aqueous, secondary aqueous humor was sampled. The samples were divided into two parts for the following measurements: one for the degree of the barrier breakdown which was represented by protein content determined by Lowry method and the other for prostaglandin content which was measured by radio-immunoassay. A significant linear relationship was obtained between the protein and prostaglandin E content but not between the protein and prostaglandin F content.


Esterase and acid phosphatase polymorphism in the fig tree (Ficus carica L.). The genetics of two enzymatic loci, esterase (Est-D) and acid phosphatase (AcP-A), were studied by means of polyacrylamide gel electrophoresis in the fig tree (Ficus carica L.). Two codominant alleles are described at the Est-D locus and four codominant alleles at the AcP-A locus. Heterozygotes at the AcP-A locus have a hybrid band, thus showing that the AcP-A allozymes, are at least dimer molecules. Both loci are independent of the male sterility factor in F. carica. The polymorphism in four natural populations was investigated for both loci. A significant deficiency of heterozygotes was observed.


Heme content of normal and porphyric cultured skin fibroblasts. Partial deficiencies in enzyme activities of the heme biosynthetic pathway have been demonstrated in cultured skin fibroblasts and other tissues from patients with protoporphyria (PP) and acute intermittent porphyria (AIP). We have quantitatively and qualitatively assessed the heme and free porphyrin content in cultured PP, AIP, VP (variegate porphyria, in which an enzymatic deficiency has not been identified), and normal skin fibroblasts during routine culture conditions in order to assess the overall metabolism of heme in these cells. The total heme concentration was not significantly different between control and porphyric lines; 189 +/- 15 pmoles/mg protein (mean +/- SEM) in controls, 154 +/- 17 in PP, 175 +/- 20 in AIP, and 181 +/- 81 in VP. The hemoprotein difference spectra were similar in all lines. Free porphyrins were not detected in any of the disorders. Despite partial deficiencies in enzyme activities of the heme pathway, porphyric fibroblasts thus maintain normal heme content during routine culture conditions without detectable porphyrin accumulation.


Duplicate gene expression in diploid and tetraploid loaches (Cypriniformes, Cobitidae). Botia macracantha and B. modesta have been demonstrated to be tetraploid species on the basis of their karyotypes and on the basis of the expression of a number of isozymes encoded by duplicate loci. A rather low percentage of duplicate loci was detected by electrophoresis, compared to that for other tetraploid Cypriniformes. Several hypotheses have been advanced to account for the low levels of duplicate gene expression observed. Lastly, many of the duplicate loci have diverged to unique patterns of expressions in different tissues or different levels of activity within a single tissue.


Homozygotes for the hereditary persistence of fetal hemoglobin: the ratio of G gamma to A gamma chains and biosynthetic studies. Two sons of a previously reported Ghanaian homozygote for the hereditary persistence of fetal hemoglobin (HPFH) (Ringelhann et al., 1970) also are HPFH homozygotes. In addition, another unrelated adult Ghanaian homozygote has been detected. All of these Ghanaian homozygotes as well as three American Black HPFH homozygotes have the G gamma A gamma type of HPFH with a G gamma to A gamma ratio of about 3:2, in contrast to an Asiatic Indian homozygote who has the G gamma type. Globin chain synthesis in HPFH homozygotes is unbalanced, with a gamma/alpha ratio of 0.6 or less, whereas it is balanced in heterozygotes according to most reports.


Membrane function in cystic fibrosis. II. Methionine transport in normal and cystic fibrosis fibroblasts. Initial rate kinetics of methionine transport, time course of accumulation of methionine, and efflux of accumulated methionine were studied in three normal and four CF human diploid fibroblast strains. The range of apparent Km's was 12.7-32.1 micrometer for the CF strains and 18.3-39.2 micrometer for the normal strains. The range of apparent Vmax's was 6.69-9.22 nmole mg-1 min-1 for the CF strains and 5.59-7.87 nmole mg-1 min-1 for the normal strains. The patterns of accumulation and efflux are quite similar in all the strains studied except for WI-38, which showed somewhat higher efflux and lower accumulation than for others. There was no significant difference in the kinetic parameters of methionine transport between CF and normal skin fibroblasts, and methionine transport will not serve as a marker for cystic fibrosis in cultured fibroblasts.


Genotypes of esterase II determined from frass of Anthonomus grandis Boh. (Coleoptera, Curculionidae). Esterase II was separated, using gel electrophoresis, from the frass of the cotton boll weevil, allowing genotyping of the individual weevil. The method and its application are discussed.


Induction of the alcohol-metabolizing pathway in the nematode Panagrellus redivivus: phenotypic effects. Panagrellus redivivus when placed in 7% ethanol or methanol becomes immobile. After 1 hr the animals resume normal swimming and will grow in alcohol. The ability to recover requires ADH activity and translation, but not transcription, as determined by inhibitor studies. Recovery decreases with longer-chain alcohols, with a greater recovery for branched rather than n-alcohols. Coincident with recovery is a threefold increase in alcohol dehydrogenase and aldehyde dehydrogenase activity. A model involving posttranscriptional control of the levels of these enzymes is presented.


The separation and characterization of bronchial glycoproteins by density-gradient methods. 1. Sputum samples from a total of 18 asthmatic and chronic bronchitic patients were examined by analytical density-gradient ultracentrifugation. CsBr was used as the dispersal agent and dense electrolyte. 2. The patterns show two main groups of components, banding at about 1.3g/ml and 1.5g/ml; in addition, a few samples showed a further zone at approx. 1.65g/ml. These components were identified as protein, secretory glycoprotein and DNA respectively. The glycoprotein zone was frequently hypersharp, and usually contained two or more partially resolved bands; it was always well resolved from the protein. 3. The glycoprotein components were isolated from nine representative sputum samples by density-gradient ultracentrifugation on a preparative scale. Analytical density-gradient ultracentrifugation was used to monitor the efficiency of the separations. 4. Some sputum samples separated cleanly under these conditions, the glycoprotein being essentially devoid of free protein; in others, separation was apparently incomplete, although computer simulation indicated that the conditions were adequate to ensure separation. Further density-gradient separations in CsCl were necessary with several samples before satisfactory products were obtained; mixtures of CsCl with guanidinium chloride were no more effective than CsCl alone. The reluctance to separate indicates a very strong, but non-covalent, interaction between protein and glycoprotein, probably associated with the gelatinous character of the secretion. 5. The purified glycoprotein components were characterized analytically and physicochemically. They contained N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and N-acetylneuraminic acid, and had an amino acid composition in which serine, threonine and proline predominated; however, aspartic acid, glutamic acid and cystine were also appreciable. The glycoproteins were of very high molecular weight, and usually showed more than one component in sedimentation velocity; their distribution in a density gradient indicated a substantial, but largely monotonic, density heterogeneity. 6. Thiol reduction decreased the molecular weight very substantially, but the products were relatively more homogeneous than the native materials. The amino acid composition was changed significantly and a small and variable proportion of protein or peptide was liberated. It is concluded that the native materials are disulphide-linked aggregates, probably through a cross-linking peptide, in confirmation of earlier studies.


Enzymic and immunochemical properties of lysozyme. Accurate definition of the antigenic site around the disulphide bridge 30-115 (site 3) by 'surface-simulation' synthesis. 1. Previous reports from this laboratory have shown that both Lys-33 and Lys-116 are parts of an antigenic site in native lysozyme. Similar studies of tyrosine derivatives indicated that one or both of Tyr-20 and Tyr-23 are located in or very close to an antigenic site in lysozyme. The site, which was located around the disulphide bridge 30-115, was recently shown unequivocally to include the residues Tyr-20, Arg-21, Lys-116, Asn-113, Arg-114, Phe-34 and Lys-33. This was confirmed by the ;surface-simulation' synthetic approach that we have recently developed, in which the foregoing eight surface residues were directly linked via peptide bonds, with intervening spacers where appropriate, into a single peptide. The peptide does not exist in native lysozyme, but simulates a surface region of it. 2. In the present work several surface-simulation peptides were synthesized representing various parts of the region, to determine the minimum structural feature that retains full antigenic reactivity and to investigate if the spatially constructed antigenic site has a preferred direction. 3. The peptide Lys-Asn-Arg-Gly-Phe-Lys exhibited a remarkable inhibitory activity towards the immune reaction of lysozyme and accounted entirely for the maximum expected reactivity of the site in the native protein (i.e. about one-third of the total lysozyme reactivity). An immunoadsorbent of the peptide bound about one-third of the total antibody to lysozyme. 4. The residues Tyr-20 and Arg-21 are not part of the site. The previously reported immunochemical effect observed on nitration of Tyr-20 was due to a deleterious ionic effect exerted by the modified tyrosine residue on the adjacent Lys-96, which is in an entirely different antigenic site of lysozyme. Thus the modification of Tyr-20 impairs the reactivity of an adjacent antigenic site, even though the residue itself is not part of a site. The conformational and immunochemical implications of this finding are discussed. 5. The antigenic site therefore comprises the five spatially adjacent residues Lys-116, Asn-113, Arg-114, Phe-34, Lys-33. The antigenic site exhibited a preferred direction (Lys-116 to Lys-33), since the reverse surface-simulation synthetic sequence was immunochemically inefficient. The site describes a line which circumscribes part [2.1nm in C((alpha))-C((alpha)) distance from Lys-116 to Lys-33] of the surface of the molecule.


The deoxyribonucleic acid polymerases from the diatom Cylindrotheca fusiformis. Partial purification and characterization of four distinct activities. Four extramitochondrial DNA polymerases from the marine photosynthetic diatom Cylindrotheca fusiformis were isolated and purified more than 1200-fold by chromatography on DNA-cellulose and DEAE-Sephadex. The enzymes were equally susceptible to inhibition by the thiol-blocking agents N-ethylmaleimide and p-chloromercuribenzoate, the zinc chelator o-phenathroline, and the nucleic acid interchelators ethidium bromide and acriflavin; they displayed similar pH optima, preferred activated DNA, and had strict dependence on high K+ for maximum activity. They were differentiated on the basis of their kinetic parameters, template-primer utilization and salt requirements. The four activities varied with growth stage of C. fusiformis. Activities of polymerases A and D doubled in exponential-phase cells as compared with those in stationary-phase cells, and the increase in polymerase B and chloroplast activity C was 20-40%. The relationship of the diatom polymerases to the complements in other organisms is discussed.


The deoxyribonucleic acid polymerases from the diatom Cylindrotheca fusiformis. Subcellular distribution, exonuclease activity and heterogeneity of the enzymes. Four DNA polymerases from the marine diatom Cylindrotheca fusiformis, polymerases A, B, C and D, were further differentiated by their subcellular localization, presence of deoxyribonuclease activity, apparent heterogeneity and molecular weights. Polymerases A, B and D occur in significant amounts in the soluble fraction, suggesting that they were originally localized in the nuclei, whereas polymerase C predominates in the chloroplasts. A mitochondrial DNA polymerase was also isolated and characterized by ion-exchange chromatography. Polymerase D has an associated nuclease activity which prefers denatured DNA and Mg2+, and has a pH optimum higher than that for polymerase activity. Co-elution from a DEAE-Sephadex column and co-sedimentation in glycerol density gradients of deoxyribonuclease and polymerase D activity suggest a molecular association. Polymerases A, B and C are devoid of nuclease activity. Glycerol-gradient-sedimentation analysis showed that all DNA polymerase fractions are heterogeneous at low ionic strengths, with the appearance of a single homogeneous activity of 0.5M-KCl. Estimated molecular weights of 100000, 82000 and 120000 for polymerases A, B and C respectively were obtained from sedimentation analysis and gel filtration. Polymerase D was estimated to have a molecular weight of about 100000 as determined by sedimentation analysis alone.


The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan structure and its susceptibility to proteolysis. 1. Proteoglycan was obtained from bovine nasal cartilage by a procedure involving sequential extraction with a low-ionic-strength KCl solution, then a high-ionic-strength CaCl2 solution. Purification was by CsCl-density-gradient centrifugation. 2. The CaCl2- extracted proteoglycan was subjected to proteolytic degradation by papain, trypsin, cathepsin D, cathepsin B, lysosomal elastase or cathepsin G. Degradation was allowed to proceed until no further decrease in viscosity was detectable. 3. The size and chemical composition of the final degradation products varied with the different proteinases. Cathepsin D and cathepsin G produced glycosaminoglycan-peptides of largest average size, and papain produced the smallest product. 4. The KCl-extracted proteoglycan was intermediate in molecular size and composition between the CaCl2-extracted proteoglycan and the largest final degradation products, and may have been formed by limited proteolysis during the extraction procedure. 5. It is postulated that the glycosaminoglycan chains are arranged in groups along the proteoglycan core protein. Proteolytic cleavage between the groups may be common to the majority of proteinases, whereas clevage within the groups is dependent on the specificity of each individual proteinase.


The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan heterogeneity and the pathway of proteolytic degradation. 1. CaCl2-extracted proteoglycan from bovine nasal cartilage was degraded by four tissue proteinases till no further decrease in hydroynamic size was obtained. The proteoglycan and its final degradation products were then fractionated by Sepharose 2B chromatography. 2. The average size of the degradation products was least for cathepsin B and lysosomal elastase, and greatest for cathepsin D and cathepsin G. The latter two proteinases also produced degradation products that showed the widest range of sizes. 3. The structure of the degradation products ranged from peptides containing a single glycosaminoglycan chain to those containing twelve or more chains. Of the four proteinases, only cathepsin B produced peptides that contained a single chondroitin sulphate chain. 4.  The proteoglycan was very heterogeneous with respect to size and chemical composition. Its behaviour on electrophoresis suggested that at least two genetically distinct core proteins might exist. 5. Irrespective of their structural variations, all proteoglycan molecules were able to interact with hyaluronic acid. In contrast, none of the degradation products were capable of this type of interaction. 6. A pathway for the proteolytic degradation of proteoglycans is postulated in which the sites of initial cleavage may be common to the majority of proteinases, whereas the production of the final clusters is dependent on the specificity of the proteinase. Only those proteinases of broadest specificity can produce single-chain chondroitin sulphate-peptides.


Biosynthesis of the first component of complement by human fibroblasts. 1. Haemolytic activity corresponding to that of the first component of complement (C1) was synthesized and secreted by all nine human fibroblast cell lines examined. No activity was found in the culture media of a variety of other human cell lines. 2. The component-C1 haemolytic activity secreted by the fibroblast lines behaved in an identical manner, in most respects, with that of the component-C1 haemolytic activity of human serum. The component-C1 haemolytic activity secreted by fibroblasts, however, was less susceptible to inhibition by rabbit fragment F(ab')(2) anti-(human subcomponent C1q) than was the component-C1 haemolytic activity of human serum. 3. Biosynthesis of fibroblast component-C1 haemolytic activity was inhibited by the presence of cycloheximide and regained on its removal. 4. Incorporation of radioactivity into proteins secreted by the fibroblasts and release of component-C1 haemolytic activity by the fibroblasts both increased in a linear manner until several days after the cultures had reached a state of confluent growth. 5. Radioactivity was incorporated into subcomponents C1q, C1r and C1s, as judged by the formation of specific immunoprecipitates and by absorption with immune aggregates. 6. The immunoprecipitates formed by using antisera against subcomponents C1r and C1s were run on polyacrylamide gels in sodium dodecyl sulphate, and this provided convincing physiochemical evidence for the biosynthesis of these subcomponents de novo. 7. The results obtained with immunoprecipitates formed by using anti-(subcomponent C1q) suggest that subcomponent C1q may be synthesized and secreted by fibroblast cell lines in vitro, in a form with a higher molecular weight than that of subcomponent C1q which is isolated by conventional techniques of protein fractionation from fresh serum.


The interaction of protein A and Fc fragment of rabbit immunoglobulin G as probed by complement-fixation and nuclear-magnetic-resonance studies. Protein-A-Fc-fragment complexes were observed in sedimentation-velocity experiments by ultracentrifugation. The interaction was studied by protein-fluorescence-quenching titrations of the Fc fragment with protein A, allowing the dissociation constant to be determined under a variety of conditions. The first component of the complement pathway, C1, is activated by complexes of protein A with rabbit IgG (immunoglobulin G), and the structural basis for this interaction was studied by using n.m.r. (nuclear magnetic resonance). The four Fc-fragment binding sites on protein A were shown to contain aromatic amino acids, and to be connected by mobile hydrophilic regions. Neither n.m.r. nor proton-relaxation-enhancement studies show evidence of a large conformational change of the Fc fragment on binding protein A, and this suggests that the cross-linking of the Fc fragments may be primarily responsible for the activation of component C1. This is supported by the inability of a univalent tryptic fragment of protein A to activate complement fixation by rabbit IgG.


The properties of a carboxylesterase from the peach-potato aphid, Myzus persicae (Sulz.), and its role in conferring insecticide resistance. Carboxylesterases from different strains of Myzus persicae were examined to try to understand their contribution to insecticide resistance. Preliminary evidence that they are involved comes from the good correlation between the degree of resistance and the carboxylesterase and paraoxon-degrading activity in aphid homogenates. Furthermore the carboxylesterase associated with resistance could not be separated from the insecticide-degrading enzyme by electrophoresis or ion-exchange chromatography. Homogenates of resistant aphids hydrolysed paraoxon 60 times faster than did those of susceptible aphids, yet the purified enzymes from both sources had identical catalytic-centre activities towards this substrate and also towards naphth-1-yl acetate, the latter being hydrolysed by both 2x10(6) times faster than paraoxon. These observations provide evidence that the enzyme from both sources is identical, and that one enzyme hydrolyses both substrates. This was confirmed by relating the rate of paraoxon hydrolysis to the rate at which paraoxon-inhibited carboxylesterase re-activated. Both had the same first-order rate constant (0.01min(-1)), showing clearly that the hydrolysis of both substrates is brought about by the same enzyme. Its K(m) for naphth-1-yl acetate was 0.131mm, and for paraoxon 75pm. The latter very small value could not be measured directly, but was calculated from substrate-competition studies coupled with measurements of re-activation of the diethyl phosphorylated enzyme. Since the purified enzymes from resistant and susceptible aphids had the same catalytic-centre activity, the 60-fold difference between strains must be caused by different amounts of the same enzyme resulting from mutations of the regulator gene(s) rather than of the structural gene.


Purification and properties of the hexosaminidase A-activating protein from human liver. Human liver extracts contain an activating protein which is required for hexosaminidase A-catalysed hydrolysis of the N-acetylgalactosaminyl linkage of G(M2) ganglioside [N-acetylgalactosaminyl-(N-acetylneuraminyl) galactosylglucosylceramide]. A partially purified preparation of human liver hexosaminidase A that is substantially free of G(M2) ganglioside hydrolase activity is used to assay the activating protein. The proceudres of heat and alcohol denaturation, ion-exchange chromatography and gel filtration were used to purify the activating protein over 100-fold from crude human liver extracts. When the purified activating protein is analysed by polyacrylamide-gel disc electrophoresis, two closely migrating protein bands are seen. When purified activating protein is used to reconstitute the G(M2) ganglioside hydrolase activity, the rate of reaction is proportional to the amount of hexosaminidase A used. The activation is specific for G(M2) ganglioside and and hexosaminidase A. The activating protein did not stimulate hydrolysis of asialo-G(M2) ganglioside by either hexosaminidase A or B. Hexosaminidase B did not catalyse hydrolysis of G(M2) ganglioside with or without the activator. Kinetic experiments suggest the presence of an enzyme-activator complex. The dissociation constant of this complex is decreased when higher concentrations of substrate are used, suggesting the formation of a ternary complex between enzyme, activator and substrate. Determination of the molecular weight of the activating protein by gel-filtration and sedimentation-velocity methods gave values of 36000 and 39000 respectively.


Interaction of cartilage proteoglycans with hyaluronic acid. The role of the hyaluronic acid carboxyl groups. Hyaluronic acid-derived oligomers of five to fifteen repeat dissaccharides effectively bind to bovine nasal-cartilage proteoglycan and inhibit the interaction between proteoglycans and high-molecular-weight hyaluronic acid. If, however, the hyaluronic acid oligosaccharides are modified by reaction with diazomethane to form the carboxyl methyl esters of the glucuronic acid residues, their inhibitory activity is abolished. The binding capacity can be fully restored by saponification. The amide derivative, which is formed by condensation of the oligosaccharide carboxyl groups with glycine methyl ester, is also ineffective in blocking the proteoglycan-hyaluronic acid interaction. In this case, binding activity is not restored when the amidated oligomers are subjected to saponification to yield the free carboxylate groups on the glycine residues. Thus the displacement of the carboxylate groups on the polysaccharide chain by the interposition of a glycine residue blocks the interaction between the proteoglycans and the hyaluronic acid oligomers. When the oligosaccharide methyl ester is reduced with NaBH4, the resultant glucose-containing oligomers exhibit decreased binding to proteoglycans. Thus it appears that the hyaluronic acid carboxylate anion in a specific spatial orientation is required for hyaluronic acid-proteoglycan interaction.


Preparation and characterization of substrates suitable for the study of stereospecific secondary alkylsulphohydrolases of detergent-degrading micro-organisms. During the course of the purification of novel stereospecific secondary aklylsulphohydrolases present in certain detergent-degrading micro-organisms, it became apparent that substrates prepared by sulphating secondary alcohols with H2SO4 are heterogeneous. Apart from the racemization that occurs if resolved alcohols are sulphated, evidence is provided to show that other isomers are produced in which the position of the ester sulphate group on the alkyl chain has been altered. These changes can be avoided if pyridine/SO3 reagent (prepared with SO3) is substituted as sulphating agent. Experiments in which secondary alkyl sulphates prepared by both methods were tested as potential substrates for the two secondary alkylsulphohydrolase enzymes of Comamonas terrigena have provided initial information about the specificity of the enzymes.


Purification, properties and cellular localization of the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena. The availability of homogeneous samples of the potassium salts of L- and D-octan-2-yl sulphate has enabled the separation of the optically stereospecific CS1 and CS2 secondary alkysulphohydrolases from extracts of cells of Comamonas terrigena. The CS2 enzyme was purified to homogeneity, and an initial study was made of its general properties, specificity, cellular localization and relationship to the CS1 enzyme. The CS2 enzyme has a molecular weight of approx. 250000 and a subunit size of approx. 58000, indicating that the molecule is a tetramer. Under the experimental conditions used the enzyme appears to be specific for (+)-secondary alkyl sulphate esters with the sulphate group at C-2 and with a chain length of at least six carbons. Enzyme activity towards racemic C-2 sulphates increases with increasing chain length up to C10, and there is some indirect evidence to suggest that activity declines when that chain length is exceeded. Other indirect evidence confirms that the CS1 enzyme exhibits similar specificity, except that only (-)-isomers can serve as substrates. Both enzymes are present in broth-grown stationary-phase cells of C. terrigena in approximately equal amounts.


Heterogeneity of rabbit muscle creatine kinase and limited proteolysis by proteinase K. By using sodium dodecyl sulphage/polyacrylamide-gel electrophoresis it was shown that rabbit muscle creatine kinase, both in a homogenate and purified, appears to be composed of a mixture of two peptides (mol.wts. 42100 and 40300) differing in length by about 15 amino acids. It is found that low concentrations of proteinase K from the fungus Tritirachium album can cleave about 38 amino acids from each chain of creatine kinase, leaving two large fragments (mol.wts 37700 and 35500). Scission of the whole enzyme was found to be concomitant with complete loss of enzyme activity. MgADP in the presence of absence of creatine slowed the rate of proteolysis by about 50%, but the transition-state analogue complex creatine-NO3--MgADP appeared to protect completely. The time course for the proteolytic inactivation in the presence of this complex, but not in its absence, was biphasic.


The nature of the circular-dichoric spectra of complexes between ribonuclease A and nucleotides. The circular-dichroism and proton-magnetic-resonance spectra of complexes of ribonuclease A with dihydrouridine 3'-phosphate, 2'- and 3'-CMP, arabinosyl-3'-CMP, 1-(2-hydroxyethyl)cytosine 2'-phosphate and 1-(3-hydroxypropyl)cytosine 3'-phosphate were studied. Comparison of the results shows that non-additivity of the circular-dichroic spectrum of an enzyme-nucleotide complex may be due to: (a), alteration of the circular dichroic spectrum of the nucleotide under the influence of the asymmetric protein matrix (induced dichroism), and (b) a change in the nucleotide conformation. The contribution of each of the two factors was estimated to calculate the circular-dichoroic spectra of 2'-CMP and 3'-CMP in complex with ribonuclease A. 3'-CMP in this complex was characterized by negative circular dichroism in the long-wavelength absorption band of the nucleotide, whereas 2'-CMP was characterized by positive circular dichroism. Since both nucleotides in the complex are known to be in an anti conformation, it follows that even small changes in the conformation considerably modify the circular-dichroic spectrum of the nucleotide in complex with the enzyme.


The arrangement of substrate and organophosphorus-inhibitor leaving groups in acetylcholinesterase active site. The leaving groups of serine esterase substrates and organophosphorus inhibitors bind to different loci at the enzyme active site. Kinetic proof of this general conclusion is presented in the case of acetylcholinesterase reactions. The proposed model for acetylcholinesterase active site provides a new stereochemical mechanism for the phosphorylated enzyme reactivation.


Phosphorus nuclear-magnetic-resonance studies of the transition-state analogue complex of creatine kinase. 31P nuclear-magnetic-resonance spectra of MgADP bound to creatine kinase in the presence of creatine NO3- ions show that there are two non-identical forms of the bound nucleotide. The sites have different affinities for the nucleotide. MgADP at the high-affinity site is in slow exchange (k less than 125s-1 at 27 degrees C) with free MgADP.


The mechanism of action of primary alkylsulphohydrolase and arylsulphohydrolase from a detergent-degrading micro-organism. Previous studies have shown that secondary alkylsulphohydrolases from certain detergent-degrading micro-organisms are unusual esterases in that they catalyse fission of the C-O bond of the alkyl sulphate ester linkage. The position of bond fission catalysed by a primary alkylsulphatase and an arylsulphohydrolase present in Pseudomonas C12B has now been investigated. The primary alkylsulphatase behaved like the secondary alkylsulphohydrolases in cleaving the C-O bond of potassium heptan-1-yl sulphate. In contrast, the arylsulphohydrolase, in common with other similar enzymes previously studied, catalysed the fission of the O-S bond of potassium p-nitrophenyl sulphate.


Rate-limiting steps in the cytidine pathway for the synthesis of phosphatidylcholine and phosphatidylethanolamine. An analysis of the available data on the cytidine pathway for the synthesis of phosphatidylcholine and phosphatidylethanolamine, by the logic derived from the theoretical principles of metabolic regulation, shows that the first two reactions catalysed by choline (ethanolamine) kinase and phosphocholine (phosphoethanolamine) cytidylyltransferase are rate-limiting, whereas the phosphocholine (phosphoethanolamine) transferase step is near equilibrium in rat liver.


Echocardiographic assessment of left ventricular filling after mitral valve surgery. In order to investigate the functional effects of mitral valve surgery, echocardiograms showing left ventricular dimension were recorded and digitised in 14 normal subjects and 129 patients after mitral valve surgery. Measurements were made of peak rate of increase of dimension (dD/dt) and duration of rapid filling, studies on left ventriculograms in 36 patients having shown close correlation between these values and changes in cavity volume. In 14 patients with mitral stenosis, peak dD/dt was reduced to 7-2 +/ 1-5 cm/s, and filling period prolonged to 330 +/- 65 ms, compared with normal (16-0 +/- 3-2 cm/s, and 160 +/- 50 ms, respectively), and after mitral valvotomy, these values improved significantly (10-4 +/- 2-7 cm/s and 245 +/- 55 ms). Characteristic abnormalities were found in 67 patients with mitral prostheses. Values for the Björk-Shiley (10-5 +/- 4-2 cm/s and 180 +/- 80 ms) and Hancock (10-3 +/- 3-7 cm/s, 245 +/- 80 ms) values were similar, and both superior to the Starr-Edwards (7-4 +/- 3-0 cm/s, 295 +/- 105 ms). Results after mitral valve repair in 30 cases were not significantly different from normal (14-4 +/- 5-0 cm/s, 170 +/- 50 ms). Values outside the 95 per cent confidence limits for the valve in question allowed diagnosis of value malfunction in 18 cases. The method is value in comparing different operative procedures and in following up patients after mitral valve surgery.


Relation between phasic mitral flow and the echocardiogram of the mitral valve in man. Ten patients without valvular disease were studied by ventriculography, and the rate and pattern of phasic blood flow into the left ventricle were determined by ventricular volume determinations at intervals of 33 ms during a single diastolic filling period. The derived left ventricular inflow patterns were then compared with the echocardiographic mitral EF slope obtained no more than 25 minutes before left ventriculography. The steepness of the EF slope was found to be inversely correlated with the time required to reach peak inflow velocity (r = 0.80, P less than 0.01) and directly correlated with the peak left ventricular inflow velocity divided by the time required to reach peak velocity (r = 0.72, P less than 0.05). No correlation was found between mean flow velocity into the left ventricle and the EF slope (r = 0.40, P = NS). A significant inverse correlation was found between the EF slope and the fraction of the diastolic filling period elapsed when 50 per cent of the filling volume had entered the left ventricle (r = 0.85, P less than 0.01). These findings suggest that the time required to reach left ventricular peak inflow velocity is one of the determinants of the mitral EF slope.


Plasma catecholamine levels and cardiac rhythm before and after cardiac catheterisation. Plasma catecholamine concentrations were estimated in a group of 17 fasting patients immediately before and 3 days after cardiac catheterisation. At both times electrocardiograms were recorded and blood pressures, heart rates, and respiration rates measured. Control catecholamine values were established in a group of 10 male and 10 female volunteers, bled at the same time of day under the same conditions of nutrition and posture. Levels of adrenaline and noradrenaline were increased substantially before catheterisation; 3 days later, the values were comparable to those of the control group, though still marginally higher. The increments in catecholamine levels were independent of sex and of the presence or otherwise of persistent supraventricular arrhythmias. In spite of the considerably raised catecholamine levels, electrocardiographic patterns remained unchanged, as did the other physiological values. The absence of any relation between enhanced catecholamine secretion and physiological effects is considered to be the result either of enhanced parasympathetic activity or of adaptation to a prolonged period of stress.


Suppression of refractory arrhythmias by aprindine in patients with the Wolff-Parkinson-White syndrome. Four patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome were refractory to conventional pharmacological therapy and received aprindine hydrochloride intravenously and orally. Electrophysiological studies disclosed that intravenous aprindine caused increased refractoriness and slowed conduction in the atria, atrioventricular node, ventricles, and accessory pathway. The ability to induce supraventricular tachycardia with timed atrial and ventricular premature stimuli was totally abolished in all 4 patients after intravenous aprindine. Oral aprindine therapy, twice daily thereafter, provided symptomatic relief of the supraventricular tachycardia without significant side effects. Aprindine is useful in the management of supraventricular tachycardia associated with Wolff-Parkinson-White and may offer significant advantages over currently available therapy.


Simple lignocaine regimen for transit to hospital after myocardial infarction. A simple combined intravenous/intramuscular regimen is described for lignocaine administration in the early vulnerable stage of myocardial infarction. Plasma levels in the therapeutic range are attained. This allows adequate drug protection during transport to hospital when an intravenous regimen may be impractical or impossible.


Type and frequency of cardiac defects in embryofetal alcohol syndrome. Report of 16 cases. Within a period of 3 years, 56 infants and children with embryofetal alcohol syndrome have been detected and examined for heart defects. All children were from mothers who had been addicted to alcohol even during pregnancy and they showed a typical pattern of malformations, as described by Lemoine et al. (1968) and Jones et al. (1973). In 16 cases cardiovascular malformations were confirmed by heart catheterisation or pathological examination. The overall incidence of heart defects in this syndrome was 29 per cent. The incidence rises to nearly 50 per cent in the more severe types of this syndrome. Atrial septal defects were found to be the most common heart defect (10 out of 16 cases); ventricular septal defects and other variable malformations occurred less frequently. The high incidence of heart defects indicates that alcoholism during pregnancy has to be considered as a serious and preventable cause of congenital heart disease.


Sudden death after operative repair of tetralogy of Fallot. The clinical and necropsy findings in 3 patients with tetralogy of Fallot who died suddenly after corrective operation are presented. Early postoperative electrocardiograms of 2 patients showed coexistent right bundle-branch block and left anterior hemiblock; one of these developed complete atrioventricular block and required a pacemaker. In the third a pacemaker. In the third patient, postoperative electrocardiograms showed anterior myocardial infarction. At necropsy, there was gross and histological evidence of myocardial infarction in each patient. After operation, extensive myocardial fibrosis and the development of right bundle-branch block and left anterior hemiblock are possible factors causing cardiac arrhythmias and sudden death.


Myocardial ultrastructural changes in Kugelberg-Welander syndrome. Electron microscopical study of a biopsied specimen of myocardium from a patient with the Kugelberg-Welander syndrome revealed myocardial degeneration, including preferential loss of myosin filaments and abnormalities in the Z bands. Leptomeric fibrils were also observed in the cardiac muscle cell; there does not appear to be a previous report of the finding of such fibrils in human myocardium.


Endocardial fibroelastosis and Niemann-Pick disease. The concurrence of endocardial fibroelastosis and Niemann-Pick disease is described. This appears to be the first described case of endocardial fibroelastosis in association with a lipid storage disorder.


Inheritance of porphyria cutanea tarda. Analysis of 14 cases in 5 families. The existence of hereditary porphyria cutanea tarda must be supported by chemical and clinical investigations capable of discriminating this porphyria from porphyria variegata, because the clinical symptoms may overlap. On the basis of such investigations (normal urinary excretion of deltaALA and of porphobilinogen; urinary excretion of large amounts of 8- and 7-carboxyl porphyrins; faecal coproporphyrin and X porphyrin fractions may be increased) we have been able to classify 14 cases, out of 200 cases of PCT that we have observed in the last 7 years, as hereditary PCT. The 14 patients belong to 5 different families: two members in each of the first three families, 3 members in the fourth, and 5 members in the fifth. In this last family heredity is bilateral.


Problems associated with ultraviolet dosimetry in the photochemotherapy of psoriasis. A hypothetical action spectrum for the regression of lesions in photochemotherapy of psoriasis is proposed. An ideal detector should have a wavelength response which matches this action spectrum but this is generally not the case with commercially available photometers. The problems that may arise by indiscriminate use of such detectors are discussed, together with a suggested solution.


Sister chromatid exchanges in lymphocytes of psoriatics after treatment with 8-methoxypsoralen and long wave ultraviolet radiation. Sister chromatid exchange rates in cultured cells from the blood of patients receiving photochemotherapy have been examined as an indicator of possible genetic hazards of the treatment to patients with psoriasis. Lymphocytes of untreated patients with psoriasis appear to have sister chromatid exchange rates after 72 h of culture indistinguishable from normal subjects and there is no evidence from these studies that sister chromatid exchanges are significantly increased in the lymphocytes of patients receiving photochemotherapy. Cells from blood taken from patients who had been given 8-methoxypsoralen orally 2 h before and then irradiated with UV-A in vitro were found to have an increased exchange rate which could be related to the presence of the drug in the peripheral circulation.


The treatment of erythropoietic protoporphyria. Experience with beta-carotene. In a group of 19 subjects suffering from erythropoietic protoporphyria the administration of beta-carotene appeared to produce improvement based on a subjective assessment of alterations in exposure times required to produce the symptoms and signs of the condition. This clinical improvement however failed to show a direct correlation with the prophyrin levels in blood and faeces, or with the estimation by phototesting of the minimal response dose within the action spectrum of 400-600 nm.


Monobenzylether of hydroquinone. A retrospective study of treatment of 18 vitiligo patients and a review of the literature. Of 18 severely afffected vitiligo patients who used 20% monobenzylether of hydroquinone (MBEH, Benoquin) as a depigmenting agent, 8 achieved complete depigmentation after 10 months or more of use and 3 dramatic but no complete hypopigmentation. The 3 patients with no results did not use MBEH for more than 4 months. Complications were frequent particularly among those who did well, but only 1 case of contact dermatitis limited therapy. All patients who depigmented fully were very pleased with their results. As depigmentation induced by MBEH is generally irreversible, MBEH use must be reserved for induction of complete depigmentation of severely affected vitiligo patients who cannot or do not choose to repigment and who can accept the permanence of never tanning. The history, histology and mechanism of MBEH depigmentation are discussed.


Pigmented neurofibroma.

Pigmented neurofibroma. Pigmented neurofibroma is a rare tumour of the dermis. The clinical features and histology of a lesion occurring in a female of 69 years are described in this report. This entity was first described by Willis in 1959 in three patients with pigmented dermal tumours which showed a plexiform structure and the presence of pseudo-Meissnerian bodies.


The successful treatment of tropical fish tank granuloma (Mycobacterium marinum) with co-trimoxazole. Three cases of tropical fish tank granuloma caused by Mycobacterium marinum (balnei) are described. Abundant acid fact bacilli were demonstrated in homogenates prepared from the fish thus providing early confirmation of the suspected clinical diagnosis: acid fast bacilli could not be demonstrated in biopsy material from the patients' lesions through M. marinum grew on culture. The infection responded to oral co-trimoxazole.


Thyroid hormones stimulate erythropoiesis in vitro. Thyroid hormones have important effects on erythropoiesis in man and animals. We performed in vitro culture studies with murine and human bone marrow in order to define the interaction of these hormones with erythroid and granulocyte-monocyte progenitor cells. The methylcellulose clonogenic assay was used with the appropriate addition of erythropoietin or colony-stimulating activity. L-thyroxine, D-thyroxine and L-triiodothyronine potentiated erythropoientin-stimulated erythroid colony formation in concentrations of 50-100 ng/ml. These hormones had no effect on granulocyte-monocyte colony formation at concentrations up to 500 ng/ml. Testing of various thyroid analogues showed no clear correlation between potentiation of erythropoiesis and known calorigenic potency. Reverse triiodothyronine also had potentiating activity in this system. The active thyroid hormones stimulated erythroid colony formation at several concentrations of erythropoietin but could not substitute for erythropoietin. These data suggest that thyroid hormones have a direct effect on erythroid precursor proliferative capacity, a finding which may have relevance to the mechanism of erythropoietic dysfunction in human thyroid disease.


The assessment of red cell survival in normal subjects and in patients with haemolytic disorders and ineffective erythropoiesis using the radioiron occupancy method. A direct method for measuring red cell lifespan in vivo using the radioiron occupancy method (Dagg et al, 1972) has been applied to eight normal subjects. The mean red cell lifespan was 116 d with a range of 104-124 d. To establish the method clinically in the presence of haemolysis and ineffective erythropoiesis, 22 patients with haemolytic disease and six patients with megaloblastic and sideroblastic anaemia were studied. All 22 patients with haemolytic anaemia had shortening of the red cell lifespan, with a range from 62 to 10 d; the results were compared with red cell lifespan derived from simultaneous radiochromium studies (Bentley et al, 1974). A close agreement between the two methods was obtained (r = 0.87; P less than 0.001). To assess the validity of the method in the presence of ineffective erythropoiesis, double isotope studies were also carried out in three patients with megaloblastic anaemia and three with sideroblastic anaemia. Close agreement was again obtained between lifespan measurements obtained from radioiron occupancy data and those derived from radiochromium studies, suggesting that the presence of significant ineffective erythropoiesis does not invalidate the method. The theoretical considerations involved in the application of the radioiron occupancy method to haemolytic states are discussed.