[Observation in a familial environment of interactions between very young children and their parents]. The interaction between very young children and their parents has been undertaken to complete earlier studies made during prolonged observations in the family home. Since 1970, several research workers collected data during fortnightly visits of variable duration. The data is briefly analysed taking into account the presence of the observers. Data was collected from families of patients with psychiatric disease and the results from those who had been seen by a Consultant were compared with those who had seen other workers. The difficulties of the first relationship are emphasised. The future of the work and possible improvements of the method are discussed as well as the educational and therapeutic consequencies.


[Unilateral interstitial emphysema in the newborn (apropos of 4 case reports)]. Four prematurely born neonates who where mechanically ventilated with CPAP for respiratory distress have developed severe unilateral pulmonary interstitial emphysema. Some particular circumstances can be pointed out in these cases. Spontaneous worsening is usual. Selective bronchial intubation protects the overinflated lung. It allowed total improvement of the lung function for the 3 cases who underwent this treatment. Although no major complications have been noticed, it is mandatory to suck out regularly bronchial secretions accumulated in the excluded lung.


[Effects of prostaglandin in heart abnormalities with needed patency of the arterial canal (clinical and histological study)]. Eight infants with cardiac malformations that were dependent on the patency of the ductus, were treated with Prostaglandin E 1 to reverse the closure of the duct. There was clinical improvement in 7 out of the 8 infants, confirmed by improvement in oxygen saturation and/or blood gases. In four cases the opening of the duct was visualised by angiography immediately after the prostaglandin infusion. Side-effects observed were transient pyrexia, flush reactions, apnoeic spells and one case of renal shock. Microscopic examination revealed in the four cases studied conspicuous edema of the media of the dictus. Because of the edema, the ductal wall is friable which indirectly may account for the severe lesions observed in the ductal wall. Prostaglandine E1 has a place in paediatric cardiology but in view of the observations made on the ductal wall it seems advisable to administer the drug only in a low dose and for a short duration.


[Recurrent hematuria in children].

[Recurrent hematuria in children]. Twenty-three children with recurrent macroscopic hematuria have been observed. Six children presented with glomerular disorder with mesangial deposits of IgG and IgA (Berger's disease). The hematuria episodes occurred in the 48 hours following an infection, more often respiratory. Renal functions were not impaired. On light microscopy, glomerular lesions were minimal, or were lesions of focal and segmental glomerulonephritis. Ten children seemed to have hereditary nephritis. In 5 cases, nephritis was accompanied by deafness (Alport's syndrome). In 5, nephritis was hereditary but isolated. The electron microscopy examination of basement membranes showed lesions consistent with Alport's syndrome. In cases of hereditary nephritis without deafness, basement membranes were less impaired. In 7 children, no specific etiology was found.


[Melitococcal hepatic encephalopathy].

[Melitococcal hepatic encephalopathy]. A 5 year old child with brucellosis is described who developed severe liver disease with neuropsychiatric signs and electroencephalographic changes.


[Factors influencing the administration of sedatives to infants and their significance]. An epidemiological survey on 1,100 young mothers has enabled the authors to carry out a study on how frequent it is for mothers to give sedatives to their infants under one year of age and on the way it can be linked with demographical, sociological and psychological factors. The longitudinal study---until they are 3---of a small group of babies has shown that practitionners asked to prescribe sedatives or sleeping pills for babies should consider it as a risk indicator.


[Partial trisomy 11 revealed by labeling technics]. A standard karyotype was normal in 1968, when performed in a girl with multiple malformations. The same investigation was performed 7 years later with labelling techniques. It showed a partial duplication of the short arm of chromosome no. 11. This emphasizes the interest of a second karyotype in clinically suggestive cases, if the first has been performed before labelling techniques were used.


[Preventive treatment with theophylline of apnea in premature infants: clinical, pharmokinetic and neurophysiological study]. Apnoea is a major problem in the neonatal paediatrics and its prevention is as important as the prevention of neonatal anoxia. The present study has three aims: 1. The strict evaluation of the results of therapy with Theophylline. 2. The determination of the pharmacokinetics of Theophylline and the establishment of the therapeutic protocol. 3. The study of the relationship between blood theophylline levels, apnoea and the states of sleep using prolonged polygraphic recordings.


[Electrolyte balance in a case of congenital chloride diarrhea]. A case of congenital chloride diarrhoea with metabolic alkalosis is reported in a 9-year-old boy who has intractable chronic diarrhoea with large watery stools from birth. Balance studies confirm the high fecal loss of chloride and the close relationship between chloride intake and fecal losses of electrolytes.


Recent results of in vitro drug prediction in human tumour chemotherapy. To assess the clinical value of the organ culture drug prediction assay in the present study we summarize the results of two randomized trials in lung carcinoma (61 patients) and ovarian carcinoma (74 patients) comparing predicted and non-predicted or no surgical adjuvant chemotherapy. No real progress could be achieved by predicted cancer chemotherapy. The reasons of the negative results of our studies are discussed.


Electron microscope study on the hepatic sinusoidal wall and fat-storing cells in the bat. The three cell types known to form the hepatic sinusoidal wall were electron microscopically observed in three kinds of bats captured in winter and summer. 1. The cytoplasmic extensions of sinusoidal endothelial cells consisted of continuous thicker parts ("cytoplasmic processes") and discontinuous thinner parts ("sieve plates"). The alternate disposition of the two parts was rather irregular, and the sizes, shapes and spacings of the fenestrae were variable. In the thinner parts with numerous small fenestrae, larger gaps were also mingled. The endothelium was simple-layered and devoid of basal lamina. Interendothelial junctions were found mainly between closely apposed margins of the "cytoplasmic processes" and agreed in structure with the "junctional complex" of WISSE (1970). 2. Kupffer cells, morphologically distinct from the endothelial cells, bulged strongly into the sinusoidal lumen. Provided with many microvillous pseudopods, they were stellate in appearance. They were fixed to the endothelial lining by small junctional areas which occurred between the Kupffer cell body and the "cytoplasmic processes" of the endothelium. 3. Fat-storing cells were located in the Disse's space. They generally contained only smaller amounts of lipid in a few droplets. So-called empty fat-storing cells were numerous, especially in winter bats. The perikaryonal cytoplasm revealed a large Golgi complex and well-developed granular endoplasmic reticulum. The three mesenchymal cell types of the sinusoidal wall possessed the centriole in common within the Golgi complex, but only the fat-storing cell was provided with the single cilium. Fat-storing cells extended cytoplasmic processes ramifying beneath the endothelial lining occasionally surrounding the sinusoids almost completely, and which seemed to reinforce the endothelial lining and to bring about the constriction of the sinusoid. In hypervitaminotic bats that daily received 6,000 I.U. vitamin A for three days, remarkable increase in size and number of lipid droplets was observed in slightly hypertrophic fat-storing cells, and the empty cells disappeared simulating an increased number of fat-storing cells. Suggestion was made of an antidotal function of fat-storing cells against excess vitamin A which might be considered a toxic agent in the broad sense. 4. The Disse's space of bat liver contained plasma cells, lymphocytes and macrophages, the latter too often being under migration through the endothelial fenestrae.


Endocrine cells in the pyloric region of the Japanese quail (Coturnix coturnix japonica). The endocrine cells of the pyloric region of the Japanese quail have been studied by light and electron microscopy. The quail pyloric region is a narrow circular zone (about 2 mm in width) between the gizzard and the duodenum. The endocrine cells are concentrated in this region, and they are represented by argyrophil cells. At least five types of endocrine cells are identified in this region by electron microscopy. Type I cells are characterized by having round and large granules (350--550 nm in diameter) whose contents are high to moderate in electron density. Type II cells are characterized by their round and medium-sized granules (250--350 nm) which possess a dense core and a clear halo. Type III cells are characterized by the presence of round and small-cored granules (150--250 nm). Type IV cells contain round and large granules (350--550 nm) of high to low electron density. Type V cells are identified by the occurrence of microfilaments and polymorphous granules of high electron density. All five cell types are recognized as open type cells. The type I, II and III cells are located mainly in the lower half portion of pyloric glands, and the other cell types are located only in the upper half portion of the glands. The type I and II cells are found much more frequently than other cell types. The relationships between the endocrine cells in the quail pyloric region and those of the mammalian digestive tracts were discussed.


Histological observations on some of the endocrine glands in the ironfish, with special regard to the hypophysis. Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.


Differences in normal structure and reaction to adjuvant between the costal and the visceral pleura. Visceral and costal pleurae of the rabbit were studied by light and electron microscopy in the normal state, after India ink injection into the pleural cavity and in pleuritis induced by intrapleurally injected adjuvant. In normal rabbits, the mesothelial cells in the visceral pleura had more numerous microvilli and pinocytotic vesicles than in the costal pleura. The surface coat on the microvilli was much thicker in the former than in the latter. Intrapleurally injected India ink particles were phagocytosed by mesothelial cells and macrophages. The phagocytotic activity was more prominent on the costal side than on the visceral side. In rabbits with adjuvant induced pleuritis, the visceral pleura, but not the costal pleura, showed mushroom-like projections on the pleural surface which were composed of a fibrin mass mixed with phagocytotic macrophages and covered by proliferative mesothelial cells. These hitherto poorly known structures, which were formed, though less conspicuously, also after India ink administration, seemed to play an important role in the initial protection of the lung against foreign body invasions from the pleural cavity. With the progress of pleuritis, the mushroom-like projections changed into patchy granulation tissues which were well localized and did not exceed the elastic layer. In the costal pleura, apparently due to a poorer protective mechanism than in the visceral pleura, granulation tissue was formed much more extensively and diffusely. No signs of transformation of mesothelial cells into fibroblasts were recognized. Fat-containing cells closely resembling the Ito cells in the liver occurred in the submesothelial and subpleural layers of the visceral pleura.


Taste buds in the vallate papillae of the rat studied with freeze-fracture preparation. The taste bud of the vallate papillae of the rat has been examined in the electron microscope by using the freeze-fracture technique. Tight junctions as a junctional complex are located at the taste pore, and form a seal between the oral environment and the taste buds. Tight junctions are not only within the taste buds, but also are demonstrated in the granular cell layers of the surrounding lingual epithelium. The present finding suggests that tight junctions of the taste pore link with those of the lingual epithelium. Desmosomes are observed in the buds, but they are smaller in size than in the surrounding lingual epithelium. Besides these junctions, within the buds, gap junctions containing particle-free zones are demonstrated which are called a subcompartment type.


The training of coordination.

The training of coordination. The training of coordination is generally considered a volitional activity, during which, by trial and perception of results, an individual selects the muscular activity resulting in the desired performance. This concept of volitionally directed complex coordination of multiple muscles with speed, skill, and strength does not stand the test of thorough evaluation. Attention is limited to 1 activity at a time, with the ability to shift attention not more frequently than 3 times per second. Only under special conditions can activity be limited to specific muscles during an untrained contraction without cocontraction of other muscles. However, with repeated practice of the desired activity, a pattern of performance is developed which can be carried out rapidly and forcefully without activation of other muscles. At that time, the consciousness is no longer directing the components of the activity but merely starting, maintaining, and stopping the performance. The development of these patterns, or engrams, by practice develops the capacity to automatically inhibit muscles that do not contribute to the performance of the desired pattern. The capacity for inhibition results in coordinated activation of the muscles contributing to the performance desired. Investigation of the development of coordination in many types of normal activities, as well as in neuromuscularly impaired patients, shows that engrams develop progressively by slow, precise practice of simple patterns, combined as they develop into more and more complex patterns, until the final skill is attained.


Significant events in the rehabilitation process: the spinal cord patient's point of view. The purpose of this study was to identify and evaluate significant events in the hospital phase of rehabilitation. Ten patients with high-level spinal cord injuries were studied 5 days a week for the entire length of their hospital stays (mean stay--109 days). Methods of identifying significant events through tape-recorded, daily logs were developed and found reliable at a level of 0.08 or higher. These events, with a net of days surrounding them, were grouped into categories, and evaluated against a control group of days--in which no significant events were identified. Four measures of depressive affect were evaluated: (1) a self report measure, (2) ratings by the hospital staff, (3) behavioral measure of verbal output, and (4) an endocrine measure, the 24-hour output of urinary tryptamine. Seventy-three percent of reactions on the dependent measures of depressive-elative affect were in the direction predicted by patient evaluations. Significant events were rank ordered according to their average rank on the 4 measures of depressive affect. There are advantages to a longitudinal, multimeasure approach to the rehabilitation career of chronically ill or injured patients.


Hemiplegic spasticity: neurophysiologic studies. The excitability of segmental reflex pathways in normal subjects and in patients with hemiplegia has been examined by conditioning the monosynaptic H reflex with a 200 msec burst of vibration applied to the tendo Achilles. In 6 normal subjects, the burst of vibration produced a short-latency facilitation of soleus motoneurons (attributed to monosynaptic excitation) which was followed by a longer-latency inhibition. A similar response was observed in 8 patients with hemiplegia, but the late inhibition was significantly less. The loss of an inhibitory mechanism may contribute to the exaggerated reflexes observed in patients with hemiplegia.


[Brain atrophy in chronic alcoholism. Clinical and computer tomographic study]. Fifty chronic alcoholics (37 men and 13 women, ages 26--55, mean age 39.9 years) with different clinical syndromes (alcoholic psychosis, alcoholic encephalopathies) were studied by computerized cranial tomography. Cerebral atrophy was detected in 96% of all cases. Combined cortical and subcortical signs were encountered in almost all cases. Cortical atrophy seemed to be detectable more easily by CT than by pneumencephalography. The computerized tomographic findings were studied in their relations to age, sex, duration of abuse, clinical syndromes, frequency of relapse (and seizures, too), etc. Cerebral atrophy was correlated primarily with the subjects' age and the duration, and less with the intensity of alcoholism. The most distinct changes were found in delirium syndromes and, in cases with relapse of psychosis, especially in combination with seizures. Wernicke-Korsakow encephalopathies showed the widest third ventricles when combined with repeated syndromes of withdrawal in their case histories. Computerized tomographic examinations of ten patients during acute psychosis as well as 4 weeks later showed identical findings; transitory changes, e.g., cerebral edema, were not detected. Computerized cranial tomography appears to be extremely useful to study the numerous open questions concerning the pathogenetic role of age, duration, and severity of abuse with cerebral atrophy.


[Idiopathic blepharospasm. Clinical and electrophysiological investigations in 27 patients (author's transl)]. Idiopathic blepharospasm is reexamined and the differential diagnosis discussed on the basis of the signs and symptoms of 27 unpublished cases. As in tardive dyskinesia, middle-aged and elderly women are mostly affected. Contrary to general opinion, spontaneous improvement occurred in about one-fifth of the patients. The habituation of the orbicularis oculi reflexes (investigated electromyographically) was diminished in 52% of the patients. These and other symptoms indicate an organic cerebral lesion as the main cause of the disease. Similarities existing between blepharospasm and torticollis spasticus are discussed.


[Investigation of the suitability of efficiency tests in evaluating endogenous depression (author's transl)]. Self-evaluation procedures are usually used to assess the severity of endogenous depression. In this respect, efficiency tests have hitherto been scarcely considered. A literary survey and our own empirical investigations suggest that self-evaluation procedures should mainly be used in mild and moderate endogenous depressions, and that these procedures give false results in severe and very severe depressions. Efficiency procedures seem not to differentiate well between 'normality' and 'mild depression,' but they become more reliable and valid for depressions of increasing severity. Self-evaluation and efficiency procedures should therefore not be substituted for each other; they should complement each other.


Adenocarcinoma of the pancreas. A ten-year experience. The experience with proved pancreatic adenocarcinoma in Portland, Ore, for 1965 through 1975 is compared with the decade 1955 through 1965. Little difference is found in time of diagnosis, incidence of resection vs bypass or laparotomy, types of resection, and overall survival. However, operative mortality improved and survival after total pancreatectomy improved from seven to 23 months. Whipple resections leave residual pancreatic tumor in one third of patients. Combining fluorouracil and radiotherapy significantly increases survival after palliative bypass (15 months vs 7.4 months, P less than .02). Based on low operative mortality, improved survival, and avoidance or residual tumor, use of total pancreatectomy as the resection of choice is recommended.


Silent perforations of the stomach and duodenum by needles. We present a series of ten patients consecutively admitted to the hospital after swallowing 12 household sewing needles. Ten of these needles, one in each patient, had perforated either the stomach or the duodenum, but in no case did the perforation cause any abdominal symptoms or signs. Immediately after arrival in the emergency ward, the diagnosis was made in most cases by means of a diatrizoate meglumine swallow, which showed the tip of the needle protruding outside the gastrointestinal tract. In the first few cases, the diagnosis was made by finding the needle in the same position after repeated plain abdominal roentgenograms. This method, however, served to delay the diagnosis of perforation. All patients were operated on immediately after the diagnosis of perforation was made, except for two who had an additional ingested needle. Operation was delayed in these patients until the second needle was spontaneously eliminated. Perforation was confirmed by operation in all cases in the present series, the operative extraction of the needle was simple, and recovery was uneventful. The fact that patients may remain asymptomatic despite perforation of their stomach or duodenum by sharp, fine foreign bodies is no cause for procrastination of surgery, as severe complications may subsequently result.


Hemodynamic effects of dopamine in septic shock with and without acute renal failure. Hemodynamic response to dopamine hydrochloride in septic shock with myocardial dysfunction was studied in ten patients with normal renal function (group 1) and in ten patients with acute renal failure (group 2). The control hemodynamic data were similar in the two groups. Dopamine in groups 1 and 2 induced significant (P less than .01) and similar increases in cardiac index and mean aortic pressure. Group 1 had a smaller increase in heart rate (+ 16%), than group 2 (+ 24%), but this difference was not significant. Stroke volume index had a significant increase in group 1 (+ 18%), whereas it did not increase significantly in group 2 (+ 4%); this difference of changes in stroke volume index between the two groups was significant (P less than .01). This phenomenon suggests an increased chronotropic effect and/or a reduced inotropic effect of dopamine in patients with septic shock and acute renal failure.


Indications, management, and complications of percutaneous subclavian catheters. An audit. A retrospective outcome-oriented audit was conducted to determine the complications associated with percutaneous infraclavicular subclavian catheters in a university hospital. The study is unique since patients having these catheters were not under the care of a select group of physicians and the patients were not restricted to a special nursing unit. One hundred and seventeen catheters were placed in 68 patients. Seventeen types of complications were audited. There were 13 complications (11%) identified as follows: pneumothorax, seven; subcutaneous emphysema, one; subclavian artery hematoma, one; pleural effusion, one; improper position, two; and sepsis, one. No mortality was associated with catheter placement. Pattern analysis suggested physician inexperience as an important cause of complications. The difficulties of establishing a retrospective audit based on documentation errors and omissions are discussed.


Cardiopulmonary bypass surgery. Platelet aggregation during induction of anesthesia and following heparinization of patients. Measurements of platelet count and platelet aggregation in response to adenosine diphosphate and epinephrine were made before and after administration of preanesthetic medications and at intervals during induction of anesthesia, before and after thoractomy, and before and after systemic heparinization in patients undergoing cardiopulmonary bypass operations. Substantial decreases in circulating platelet count occurred only after induction of anesthesia and following thoracotomy. There was no notable change in the percent of platelets involved in aggregation over the period studied, but the reactivity of platelets was increased after induction of anesthesia and after thoracotomy.


Pectus excavatum repair using autologous perichondrium for sternal support. The support of the lower sternum following repair of pectus excavatum using autologous perichondrium from the lower costal cartilages to supplement the standard Ravitch's repair has been used effectively in 29 children during the past 14 years. This technique helps prevent recurrent sternal depression, particularly when the operation is performed in preadolescent children. Most adolescents and adults with pectus deformities as well as patients requiring reoperation will benefit from an internal prosthesis for the sternum that supplements the perichondrial support to reduce the frequency of subsequent sternal depression. Using the described operative technique, an excellent cosmetic and functional result was obtained in 27 children. Recurrent sternal depression of mild degree that occurred in two patients in the first four months postoperatively was related to trauma and possibly to decreased vascular supply to the lower sternum but neither required additional therapy. The internal mammary vessels should be preserved with the lower sternum whenever feasible.


Tolerance of the human liver to prolonged normothermic ischemia. A biological study of 20 patients submitted to extensive hepatectomy. To evaluate the biological tolerance of the human liver to prolonged warm ischemia, two groups of extensive hepatic resection for tumor were compared. Group 1 (11 patients) performed with short hepatic inflow occlusion (7 [mean] +/- 2 [SEM] minutes), and group 2 (nine patients) operated with use of complete hepatic vascular exclusion and prolonged warm liver ischemia (38 [mean] +/- 5 [SEM] minutes). Comparison of biological values, such as transaminase, bilirubin, total protein, albumin, and fibrinogen levels, the platelet count, prothrombin complex, and proaccelerin level, did not show statistically significant differences between the two groups. Therefore, the hepatic warm ischemia period may be, if needed, safely extended beyond the classical 15 minutes. It lasted 65 minutes in one case without adverse effect. These clinical observations parallel recent experimental work and should destroy the myth of the high sensitivity of the liver to warm ischemia.


Congenital hepatic duct obstruction with perforate diaphragms. A patient had obstruction of the right and left hepatic ducts secondary to perforate diaphragms at the junction with the common hepatic duct. Transhepatic cholangiograms of both the right and left lobes were required to define the presence of diaphragms at the junctions of right, left, and common hepatic ducts. Excision of the diaphragms relieved the obstruction. A distinction should be made between congenital nonobstructive and congenital obstructive cystic dilation of intrahepatic biliary radicals.


Abdominal aortic aneurysm and retroperitoneal fibrosis. Ultrasonographic diagnosis and treatment. Until changes of ureteric or vascular compromise are noted, retroperitoneal fibrosis usually goes unnoticed. When symptomatic retroperitoneal fibrosis has been associated with abdominal aortic aneurysm, ureteral involvement has uniformly been present. Three cases demonstrate a new ultrasonographic picture that can aid in early identification of retroperitoneal fibrosis before complications are manifest. In patients with abdominal aortic aneurysms, routine sonography may identify unsuspected retroperitoneal fibrosis, a factor that may be important in preoperative planning for safe surgical intervention.


Acute acalculous cholecystitis. Ultrasonic appearance. Acute acalculos cholecystitis can be associated with severe electrical burns. Ultrasound can have a role in the evaluation of this problem.


Nitroprusside prevents adverse hemodynamic effects of vasopressin. The influence of vasopressin and sodium nitroprusside on liver circulation was investigated in 18 dogs. Cardiac output was determined by the thermal dilution technique using a Swan-Ganz catheter. Hepatic artery and portal vein flows were measured with electromagnetic flowmeters. The infusion of vasopressin (0.01 unit/kg/min) caused a 13% increase in mean arterial pressure, a 38% decrease in cardiac output, a 57% decrease in portal blood flow, and a 35% decrease in portal pressure. Hepatic artery blood flow initially decreased, then increased, and eventually exceeded the baseline value by 25%. The addition of sodium nitroprusside infusion (10 microgram/kg/min) returned the mean arterial pressure to baseline value and increased cardiac output to 83% of baseline value. Portal blood flow remained unchanged, even though an additional decrease in portal pressure of 11% and a further increase in hepatic artery blood flow of 45% were observed. Nitroprusside minimizes the undesirable effects of vasopressin and augments the desirable ones in normal dogs. The combination of these drugs may be more beneficial to patients with esophageal and gastrointestinal bleeding than vasopressin alone.


All pustular nodules are not bacterial.

All pustular nodules are not bacterial. A case of lymphocutaneous sporotrichosis was thought to represent bacterial pyoderma. Lack of recognition led to excessive costs and a delay in the institution of specific therapy. The differential and an approach to diagnosis of pus-containing nodules are discussed.


Effect of dietary lead on placental blood flow and on fetal uptake of alpha-amino isobutyrate. Large amounts of lead administered to pregnant mice can prevent implantation, cause embryonic death or retarded growth. Placental blood supply measured by injected radioactive microspheres is of the order of 23% of the cardiac output for a litter of eight mice on day 18 of pregnancy. In lead-treated animals, not only placental blood flow per embryo but also that per embryo weight is reduced. On the other hand, uptake of a non metabolizable amino acid, alpha amino isobutyrate is not altered by lead treatment. It is noteworthy that about 40% of this amino acid go to the embryo during pregnancy. In view of the normal substrate uptake at a reduced bloodflow it remains undecided whether an insufficient supply by the placenta or a reduction in hem synthesis described earlier is the factor responsible for the retardation in fetal growth.


Analysis of chromosomes of workers exposed to acrylonitrile. Examination of 18 workers who had been exposed to acrylonitrile for 15.3 years on average and 18 workers who had not been exposed to acrylonitrile showed no difference in the incidence of chromosome aberrations; for each person concerned 100 metaphases were evaluated.


Role of liver glutathione in 1,1-dichloroethylene metabolism and hepatotoxicity in intact rats and isolated perfused rat liver. The liver glutathione content was measured after oral administration of 1,1-dichloroethylene (vinylidene chloride = VDC; dissolved in olive oil) and its significance for the metabolism and hepatotoxicity of VDC was investigated. After treatment with 1000 mg/kg VDC p.o., glutathione decreased to 33% of the control values within 4 h but returned to the control level after 24 h. An identical fall in glutathione after VDC administration was found to occur in animals which had been fasted for 18 h. In these animals the baseline values of glutathione were lowered by 21%. The depletion of glutathione was dependent on the dosage of VDC. The conversion rate of VDC by the isolated perfused livers was 7.64 mumoles/g liver after 3 h-perfusion, if 5000 ppm of VDC were supplied in the gas phase. Lowering the glutathione content to 15% of the normal value (by diethylmaleate, 25 mumoles added directly to the perfusate) resulted in a reduction of VDC conversion by 18%. Furthermore the viability (with the lactate/pyruvate ratio serving as the parameter) of the liver was distinctly depresesd. No effect on viability nor on metabolization rate was noted when perfusing the livers of 18-h fasted animals. The concentrations of the glutamate-oxaloacetate transaminase (SGOT) and glutamate-pyruvate transaminase (SGPT) in the perfusate failed to show an increase. These findings indicate that there is no correlation between the liver glutathione level and the increased lethality of VDC in fasted rats.


Biochemical and toxicological effects of short-term, intermittent xylene inhalation exposure and combined ethanol intake. Intermittent inhalation of 300 ppm of xylene vapour 6 h daily for 2 weeks caused a marked accumulation of the solvent in the perirenal fat. Simultaneous ethanol ingestion reduced the solvent load significantly although the perirenal xylene concentration increased in both test groups between the first and second week of exposure. Xylene inhalation enhanced hepatic and renal ethoxycoumarin 0-deethylase activity about 1.5-fold. The combination of inhaled xylene and peroral ethanol showed a markedly potentiated effect on microsomal ethoxycoumarin 0-deethylase activity especially in the kidneys. The enhanced monooxygenase activity was compatible with the decreased body solvent burden. Therefore, simultaneous ethanol intake might significantly modify the toxicological hazard in xylene exposure. Slightly increased proteolysis was detected in brain of animals in the xylene-ethanol experiment after the second week. Brain RNA content decreased after 2 weeks of exposure in the ethanol consuming animals. Xylene inhalation enhanced cerebral DT-diaphorase activity in both groups after 2 weeks of exposure. Ethanol intake also potentiated the behavioural effects caused by the solvent inhalation.


Acetaldehyde level in the blood and liver aldehyde dehydrogenase activities in trichloroethylene-treated rats. The liver NAD+-dependent aldehyde dehydrogenase (AldDH) activity and the acetaldehyde level in the blood during ethanol metabolism after trichloroethylene (trichlene) exposure were studied in rats. Trichlene inhalation caused large elevations in acetaldehyde levels during ethanol metabolism and caused decreases in the activity of the AldDH with a low Km value in mitochondrial and soluble fractions of liver cells. No significant effects were found in the activity of the high Km-enzyme in mitochondrial, soluble and microsomal fractions. Time course of inhibition of the mitochondrial low Km-enzyme and that of elevations in acetaldehyde levels during ethanol metabolism after trichlene exposure were similar. These findings suggest that acetaldehyde formed from ethanol in vivo is oxidized primarily by the mitochondrial low Km-enzyme.


Neurotoxicity of organophosphorus pesticides: predictions can be based on in vitro studies with hen and human enzymes. The comparative inhibitory power of organophosphorus esters in vitro against hen brain acetylcholinesterase and neurotoxic esterase correlates with their comparative effects (death or delayed neuropathy) in vivo. Further comparisons of the in vitro effects seen with hen and human enzymes facilitates extrapolations to the human in vivo situation.


Prevention of CeCl3-induced hepatotoxicity by hypolipidemic compounds. Pretreatment of rats with nafenopin, a hypolipidemic compound, prevents the lethality and hepatotoxicity induced by cerium chloride (CeCl3), a rare earth metal. The increase in hepatic triglycerides and the morphologic changes observed after 48 h of the CeCl3 injection (10 mg/kg) are completely abolished by nafenopin given for 4 days in doses of 250 mg/kg. However, an increase in the frequency of peroxisomes is noted in rats receiving nafenopin and CeCl3, attributable to the hypolipidemic drug pretreatment. In comparing the protective effect of nafenopin with that of CPIB (a structurally related compound) and lentysine (a structurally unrelated agent), it can be seen that nafenopin is about five times more active in decreasing liver triglycerides. The hepatic ultrastructure of rats pretreated with CPIB or lentysine is similar to that of CeCl3-treated controls.


Comparison of the therapeutic effects of five antiviral agents on cutaneous herpesvirus infection in guinea pigs. Cutaneous herpesvirus infection of guinea pigs has been evaluated as a model for testing antiviral compounds. Six infected sites on each animal can be used independently for local treatment. The severity of the infection has been graded in a score system. The cumulative scores during infection and the time to healing can be used to determine antiviral effects. The effects of adenine arabinoside, cytosine arabinoside, iododeoxyuridine, ribavirin and phosphonoacetic acid on the cutaneous infection was compared. Phosphonoacetic acid was the only compound with a good therapeutic activity against herpesvirus infection, causing a reduction of both the cumulative score and the time to healing. Phosphonoacetic acid was skin irritating at 2 per cent, but at 1 per cent, which still had a good therapeutic activity, skin irritation was seen only occasionally.


Growth and genetic stability of 4 temperature sensitive (ts) mutants of respiratory syncytial (RS) virus in newborn ferrets. Four temperature sensitive (ts) mutants of respiratory syncytial (RS) virus were evaluated for growth and genetic stability in newborn ferrets. ts-1, the mutant previously tested in children as a possible live virus vaccine and found to be insufficiently attenuated for the upper respiratory tract, grew in the lungs of newborn ferrets to the same peak titer as wild type RS virus. In addition some genetic alteration of the ts-1 mutant occurred. Two more defective subclones of ts-1, ts-1 NG-1 and ts-1 NG-16, were greatly restricted in growth in the ferret's lungs. ts-1 NG-16 was also restricted in the nasal turbinates, but ts-1 NG-1 grew to high titer in the nasal turbinates. Growth of ts-1 NG-1, however, was delayed 2 weeks compared to the growth of wild type virus. Genetic alteration occurred during growth of either subclone; the virus isolated was intermediate between wild type and input virus in plaque forming ability at restrictive temperatures. In no instance was wild type virus isolated from the ferrets infected with either subclone. ts-2, a plaque morphology mutant that does not fuse cells to form syncytia even at the permissive temperature of 32 degrees C, was restricted in growth in both the lungs and nasal turbinates, and genetically altered virus was not recovered from these animals. Of the mutants tested, ts-2 was the most restricted mutant in the newborn ferret and should be evaluated further as a candidate vaccine virus.


Host range mutants of an influenza A virus. Temperature-sensitive (ts) mutants of fowl plague virus with a ts-lesion in segment 1 (ts 3, polymerase 1 gene) or segment 2 (ts 90, transport gene) do not form plaques on MDCK cells at the permissive temperature, while the wild type and ts-mutants of other groups are able to do so. This property is correlated with the ts-lesion, since revertants for the ts-lesion of ts 3 and ts 90 again form plaques on MDCK cells. The block on MDCK cells--at least for ts3--may be located in a late function, since viral RNA polymerase and hemagglutinin are formed in almost normal yields. MDCK cells infected with ts 3 or ts 90 exhibit a retarded cytopathic effect at 33 degrees C, but no cytopathic effect at 39 degrees C, at which temperature the infected cells can be passaged and super-infected with the wild type strain. Cells surviving the infection with ts 90 at 33 degrees C sometimes grow out again to a normal monolayer. It is suggested that the spread of virus is inhibited under these conditions.


Growth characteristics of influenza virus type C in avian hosts. Brief report. Influenza virus type C could be propagated to high yield in primary chick embryo kidney cell culture (PCEK) provided that trypsin (2 microgram/ml) was used as a medium supplement. The virus could also be titrated by plaque assay using PCEK host cells and influenza C virus that had been plaque-purified in PCEK cells could then be serially passaged to high titer using the allantoic route of 10--11-day-old embryonated eggs.


[Comparative study of the lymphoid organs of rats aboard a space flight under weightless and artificial gravity conditions]. A comparative histological investigation of the thymus, spleen and inguinal lymph nodes has been performed in the rats flown for 18.5 days on board the biosatellite "Cosmos-936" under the conditions of weightlessness and artificial gravitation (acceleration 1 g) imitating terrestrial magnetism. It has been stated that in the animals that were under the conditions of weightless ness during the flight and were sacrificed 4.5--13 h after they have landed the Earth, accidental involution of lymphoid organs is noted with morphological signs in them of an acute stress in the form of massive degeneration of the thymus lymphocytes and neutrophilic infiltration of the spleen. In rats that during the flight were subjected to the effect of artificial gravitation there was noted neither involution of the lymphoid organs nor morphological signs of acute stress in them. One of the main cause of acute stress in the rats subjected to weightlessness during the space flight is supposed to be transition to the terrestrial gravitation.


[Morphofunctional analysis of the microcirculatory bed following sublethal dehydration of rats]. Sublethal dehydration is followed by a considerable weight loss, drop in rectal temperature, decreasing respiratory rate, increasing tachycardia and hematocrit. Sublethal stages of dehydration result in uniform changes in the dura mater, parietal peritoneum, small intestine mesentery, muscular part of the diaphragm, the renal capsule deformation, discomplexation of microvessel networks and structural changes of microvessel walls. Microvessel morphometry has demonstrated a certain decrease in diameters of all the parts in the objects studied. Maximal decrease of the diameter has been noted in capillary and postcapillary venular parts. The greatest changes in microvessel structure has been noted in the dura mater and in the serous sheets.


[Microangioarchitectonics and microtopography of the blood vessels of the human stomach]. The data of previous investigations on general principles of microarchitectonics of the human intraorganic gastric vessels have been checked. Peculiarities of branching and course of the stomach intraorganic vessels, arterio-venous anastomoses, twisted arterioles, sinusoid venules and veins confirm activity and variability of the organ's circulation at microcirculatory level. Certain slight differences in diameters and number of microvessels have been revealed in some anatomical parts of the serous membrane and submucous layer of the stomach. Maximal differences in vessel diameters of the microcirculatory bed and in number of capillaries per 1 mm2 have been revealed in the most active layers of the gastric wall--in muscular and mucous membranes. In the muscular membrane, large vessels and greater number of capillaries have been revealed in the area of the greater curvature and the pylorus. In the serous membrane in the pyloric area and in the area of the smaller curvature, microvessels have smaller diameters and the number of capillaries per square unit is less.


[Structural organization of the intraorganic circulatory bed of the human gingiva]. By means of injected and noninjected methods, structural organization and morphological structure of some parts of the gum microcirculatory bed have been studied in 46 persons at the age of 22--76 years. It has been stated that a fixed gum is characterized by uneven vascular distribution and zonal modulation of the microcirculatory bed. Diffuse capillary surface per 1 mm2 of the fixed gum in persons at the age of 22--50 years is 0.20--0.28 mm2. The blood volume in vessels of the gum module is distributed between arterioles and precapillary arterioles (22.4%), capillaries (27.1%), venular vessels (50.5%). In the borderline parts of the fixed gum (free gum, mucous membrane of the transitional fold) there are typical capillaries of a loop-like form. In the vicinity of epithelial fixation, vascular glomeruli are situated. In the microhemocirculatory bed of the gum, precapillary sphincters and arteriolo-venular anastomoses are revealed.


[Effect of experimental resection of the pancreas on the structure of lymph nodes at the root of the small intestine mesentery]. Resection of 2/3 mass of the pancreas preserving the ducts of the central portion is accompanied in dogs by certain changes in lymph nodes of the small intestine radix mesenterii. The operative trauma is followed by size decrease of the lymph nodes owing to degeneration and migration of lymphocytes. Absorbtion of decay products from the operative wound results in lymphocytic blasttransformation and proliferation. By the end of the first and beginning of the second month of the experiment, certain involution is noted in the lymph nodes. Further regeneration of the pancreatic stem and restoration of the lymph nodes structure develop nearly simultaneously.


[Comparative anatomy of the spinal cord of semi-aquatic, aquatic and terrestrial mammals]. Skeletotopically, cervical thickening of the spinal cord in semiwater mammals (Callorhinus ursinus, Eumetopias jubatus, Phoca larga, Phoca kurilensis, Enhydra lutris) corresponds to 4--5, and in terrestrial mammals (Ursus arctos, Vulpes vulpes)--to 3--6 cervical vertebrae. Lumbar thickening in terrestrial spicies and in Enhydra lutris is situated more caudally from the thoracic portion than in Phocidae. In a typically water animal (Phocaenoides dalli) the cervical thickening is expressed feebly, the lumbar one is absent, the epidural space is developed better than in terrestrial and semiwater animals. In Phocidae, comparing terrestrial species, bringing together of the nerve fasciculi taking their origin from the spinal cord is observed, a powerful development of a "horse tail", elongation of nerve bands, going from the spinal cord to spinal ganglia. The relative length of the spinal cord in semiwater and water animals is less than in terrestrial ones. It is stated that differences in spinal cord construction and topography of the animals in question are closely connected with their environmental conditions, functional loading and locomotor peculiarities.


[Several important questions concerning the segmental structure of dog liver]. Anatomical structure of the dog liver has been studied in 82 isolated preparations. Besides the external surface of the organ, the study has been carried on in preparations of intraorganic branches of the portal vein, hepatic veins. Roentgenography of the portal vein and the hepatic artery has been performed. According to the external composition and intraorganic branching of the portal vein and the hepatic artery, two separate lobes--right and left--can be determined in the dog liver. The right lobe consists of two segments, the left one has five segments. Their classification is presented. From the left hepatic lobe, blood outflows along the hepatic veins which open into the posterior vena cava by their common orifice. The right portions of the fifth segment, segments 6, 7 are drained by veins having their own orifices. The hepatic artery has 3--4 branches: the left carrying blood to 1, 2, 3 segments, middle supplying with blood 4, 5 segments and gall bladder, one--two right branches going to 6, 7 segments.


[Several possible approaches to the interpretation of histoenzymatic reactions]. As a result of comparative histoenzymatic and electron microscopic investigations performed on the myocardium of the isolated heart, a close connection has been stated between a peculiar sedimentation of diphormasan granules and conditions of mitochondria in myocardial cells at different time of thermal cardiac ischemia. Four types of sedimentation of the products of histoenzymatic sedimentation have been revealed: diffuse-granular, granular, scattered and "secondary" diffuse. Their connection with peculiarities of energy metabolism of mitochondria and transmembrane transport is demonstrated. A possibility is suggested to use histoenzymatic reactions in order to determine vitality of conserved organs.


[Effect of age, sex and season factors on sudden death in ischemic heart disease]. Statistical analysis of 525 cases of sudden death was done on the data of forensic medical examinations of cadavers of subjects suffering from ischemic heart disease (IHD). In the structure of cases of sudden death in IHD the percentage of men was shown to be approximately twice as high as that of women. An increase in the percentage of women in older age groups and a stronger effect of the age factor in women on the frequency of sudden death in IHD were noted. There was a strong correlation between the frequency of sudden death in IHD and the heart mass. Most cases of sudden death in IHD were registered in the autumn-winter period.


[Pathomorphology of the lungs and pleural capillaries in Hamman-Rich syndrome]. Morphological changes in the lungs in Hammen-Rich disease were studied. The developing pneumosclerosis in this disease was found to be associated with the inflammatory involvement of microvessels of the alveolar parenchyma. An adaptive rearrangement of pleural microcirculatory bed vessels under these conditions was demonstrated.


[Morphology of reserve cells of the excretory ducts of esophageal mucous glands in chronic esophagitis]. Morphological, cytophotometrical, and histochemical study of reserve cells of the excretory ducts of esophageal mucous glands in chronic esophagitis was done on autopsy material (189 cases). Chronic esophagites were found to be accompaned by diverse morphological changes of reserve cells manifested in the development of their focal and diffuse hyperplasia. The reserve cells of the esophageal epithelium were found to be capable to differentiate into the squamous and glandular epithelium. Chronic esophagites were shown to cause metabolic disorders in the nuclei of the reserve cells leading to changes in the chromosome set. In the opinion of the authors, their results are important for the elucidation of the nature of esophageal adenoacanthomas.


[Differential diagnosis of epithelial tumors of the bladder by means of determination of their mitotic system]. The results of the study of the mitotic regimen (mitotic activity, ratio of mitosis phases and percentage of pathological mitoses) in epithelial tumours of the urinary bladder are presented. Different tumours of the urinary bladder were found to have their own mitotic regimen which may be used as an additional criterion in the diagnosis of epithelial tumours of the urinary bladder.


[Trichinosis-induced myocarditis].

[Trichinosis-induced myocarditis]. Trichinellosis myocarditis with the presence of juvenile forms of the parasite in the myocardium is an extremely rare pathology, according to the literature. The present observation refers to a woman of 43 who had been treated for a long time for rheumatism. In 1974, aortic valve failure was diagnosed and in September, 1976, she was sent for operative treatment. Three hours after admission she developed acute cardiac insufficiency and died. Trichinellosis myocarditis was diagnosed at autopsy.


[Cerebellar infarct in hypertensive crisis]. The paper reports an unusual pathogenetic mechanism of the cerebral circulation disorder in hypertensive crisis. Cerebellar infarction developed as a result of compression in great occipitae foramen of the inferior posterior cerebellar artery which was a complication of a severe hypertensive crisis with cerebral edema and a shift of stem structures into the great occipitae foramen. Of great importance in the parthogenesis of infarction was a rarely occuring variant of the course of the right inferior posterior cerebellar artery.


[Brief clinico-anatomical sessions as a method of familiarization of the clinicians with autopsy materials]. To bring closer the results of autopsy work to clinical and polyclinical wards of united hospitals, the authors recommend that brief weekly clinico-anatomical analyses of the autopsy material for the week be held. They may be timed with weekly general hospital conferences, and be allotted 20--30 min. On the average, 3--4 cases should be analysed with demonstration of macropreparations, organocomplexes, a brief description of pathological changes and 2--4 min of clinical information.


[Morphological characteristics of angiomyolipoma of the kidneys]. Eight cases of angiomyolipoma of the kidneys were studied. A variant of the tumour in which its vascular component consisted mostly of numerous primitive vascular fissures penetrating the smooth muscle tissue is described. In two cases, perivascular outgrowths of undifferentiated cells of apparently adventitial type were found. In most cases the mature fatty tissue of the tumour is found to have large multinucleate cells assume to be a manifestation of atypical differentiation of precursors of fatty cells. The smooth muscle tissue can be of a various degrees of maturity, and variants of angiomyolipoma may be distinguished in which the muscular component is represented either by highly a differentiated tissue, or by a immature tissue or combination of both.


[So-called medullary fibromas of the kidney]. This is the first description in the national literature of morphology of the so-called medullar fibromas of the human kidney which are considered to be hormonally-active (producing prostaglandines) tumours or tumour-like focal hyperplasias of interstitial cells of the kidney medullary layer.


[Formation and destruction of the skin collagen structures in systemic scleroderma]. Histological, electron microscopic, and morphometric studies of skin biopsies from 70 patients with systemic sclerodermia showed an increase in biosynthetic processes both in the affected and nonaffected parts of the skin. Enhanced neofibrillogenesis was found only in areas of sclerodermic lesions. Abnormalities in newly formed collagen structures as well as splitting of newly formed collagen fibrillae into microfibrillae were observed. In unaffected skin areas two types of destruction of collagen fibrillae were observed: extracellular destruction and fibroplasia.


[Cytomorphological classification of pretumorous lesions and squamous cell cancer of the cervix uteri]. A cytomorphological classification of pretumour lesions and squamous cell carcinoma of the cervix based on the determination of the degree of atypical condition and differentiation of the epithelium is proposed. This classification is an attempt to synthesize the previous cytological classifications with histological classifications of cervical lesions.


[Changes in the endometrium from the use of hormonal preparations and hormonal contraceptives]. The paper analyses changes in the uterine mucosa caused by the use of hormone drugs, including hormonal contraceptives and studied by light and electron microscopy. Special emphasis is given to changes caused by overdosage of the drugs. Long-term usage of estrogens and progesterone, both separately and particularly in combination, results in marked atrophy and slcerosis of not only uterine mucosa but also of the uterus itself. In women over 35, a long-term oral use of hormonal contraceptives may lead to the development of thromboses and thromboembolias. Therapeutic suggestions are given for different changes of the mucosa revealed by histological studies. A reliable diagnosis should be based on both morphological and functional aspects.


[Primary cancer of the duodenum].

[Primary cancer of the duodenum]. Two clinical observations of primary carcinoma of the descending branch of the duodenum in men of 39 and 58 operated for this disease are described. Histologically the tumor was papillary adenocarcinoma. No metastases into regional lymph nodes or internal organs were found. In the patient of 39 the carcinoma of the duodenum was accompanied by papillomatous outgrowths in the opening of the pancreatic duct.


Freeze fracture aspects of the spiral limbus. Replicas of the freeze fractured spiral limbus are studied in chinchillas. Zonulae occludentes are demonstrated between the interdental cells and the inner sulcus cells; gap junctions are described connecting interdental cells and inner sulcus cells to one another and they are found between the perilymphatic cells in the spiral limbus.


Equillibrium disorders with diffuse brain atrophy in long-term toluene sniffing. A Japanese male who became habituated to sniffing toluene exhibited ataxia, tremor, incoordination and equilibrium disorders. There was pendular nystagmus with a normal caloric response. There were an inhibition of optokinetic nystagmus and a failure to follow over 0.1 Hz sine waves on eye tracking test. Angiogram and pneumoencephalogram revealed an atrophy of the midbrain and cerebrum, and degeneration of the cerebellum was suspected.


The etiology of neurosensory hearing defects in preterm infants. We retrospectively investigated the influence of gestational age, perinatal risk, and the duration of incubator care periods in 193 surviving preterm infants with a gestational age between 28 and 36 weeks raised in our intensive care nursery incubators from 1965--1967. 24 (12.4%) of the children showed definite neurosensory hearing defects, which were particularly encountered in the high frequencies. No correlation could be substantiated between hearing difficulties and hyperbilirubinemia, streptomycin application and gestational age. This study does not support the assumption that the duration of noise exposure in currently used incubators is a major determinant for the development of deafness in otherwise healthy preterm infants. Our study did show, however, a strong correlation between the sum of all perinatal risk factors and neurosensory hearing loss.


[Influence of thyroid state on noise-induced cochlea damage (author's transl)]. Guinea pigs were exposed to pure tone noise (2.7 kHz, 130 dB, 1 h) and cochlear microphonic potentials were measured after 5 days. It is possible, to modify the resulting damage by experimentally altering the rate of metabolism by regulating the function of the thyroid gland. (table: see text) A hypofunction of the thyroid gland during sound exposure lessens, an over-function aggravates the damage. This effect possibly results from the influence on the metabolism exerted by the adenylic system. This conclusion leads to new viewpoints concerning prophylaxis, therapy and metaphylaxis in cases of noise deafness.


[Oxygen supply of middle- and inner ear in experimental tubar occlusion (author's transl)]. 1. The mucosa of the middle ear is not only supplied with oxygen from the blood but also from the air space of the middle ear. 2. Under physiological conditions, the perilymph is supplied partially with oxygen from the tympanic cavity. When the PO2 in the middle ear falls below 57 mm Hg, a net diffusion flux of oxygen from the perilymph to the middle ear induces a loss of oxygen from the inner ear. 3. A negative pressure of 25 mm Hg generated in the middle ear, causes a transudate. Subsequently, slight disturbances of microcirculation should occur in the mucosal membrane (pO2-histogram). More pronounced negative pressure lead to very distinct disturbances of microcirculation and local oxygen supply.


[Alcohol and balance disorders (author's transl)]. The optokinetic, horizontal, per- and postrotatoric nystagmus was recorded before the consumption of alcoholic beverages by 20 young test persons as well as 2, 4, and 6 h later. The results showed that the most evident alterations cannot be recorded during the highest blood alcohol concentration but only 6 h after the consumption of alcohol. It was evaluated that the decomposition products of alcohol provoked the vestibular disorders.


[One stage reconstruction of the trachea with an island flap (author's transl)]. After treatment of the tracheal or laryngo-tracheal stenosis and forming a groove or using Rethi's operation, putting a full thickness skin graft or mucosa into the posterior wall, we use a silicone rubber tube for dilatation. An island flap, pedicled upon the long muscles of the larynx is used for closing the defect in the anterior wall of the trachea. We treated four patients with this method, three left hospital with normal diameter of trachea and resistance between 17 and 20 mm H2O/1/s.


Electron microscope study of basophilic cells in allergic nasal secretions. In order to elucidate whether basophilic cells in nasal secretion belong to blood basophil or tissue mast cell, basophilic cells in the blood, nasal secretion, and nasal mucous membrane were electron microscopically observed in patients with house dust nasal allergy. The majority of basophilic cells in the nasal secretion was identical with the blood basophil in structure. The blood basophils pass through the vessels and emigrate in the mucous blanket in allergy.


First clinical experiences with hormone-therapy of pachydermia laryngis. First clinical experiences with the anti-androgenic drug cyproterone-acetate in treatment of pachydermia laryngis are reported in eleven male and female patients. This endocrine therapy led to complete healing in four and to marked improvement in six patients. One did not respond. Evaluation of the endocrine state of these patients showed imbalance in the androgen/estrogen equilibrium. As the larynx constitutes a secondary sex characteristic and an endocrine target organ, the significance of endocrine factors for pathogenesis and therapy of epithelial changes on the vocal cords is discussed.


Recognizing and helping narcotic addicts in general practice. It is rare for many general practitioners to be consulted by a narcotic addict. It can be a disturbing experience. Those who practise in urban areas of low socioeconomic status where there is high youth unemployment are more likely to meet addicted young people, but the experiences are uneven, even in this context.


Heroin addiction: what can the GP do?

Heroin addiction: what can the GP do? This article is based on nine months as a casualty coordinator, and eighteen months of weekly GP sessions at a drug dependency unit--a limited experience which justifies no claim to expertise. However, I believe my former ignorance to be fairly typical, so that my comments may have value for GPs. Although the comments focus on heroin (this being by far the most common narcotic of addiction), I am aware that heroin fits into a long continuum of substance dependencies, perhaps offers an entry into that continuum for the clinician who seeks understanding of all dependencies. My object being to describe the landscape through the eyes of a GP taking his first real look, I shall concern myself with concepts and impressions rather than statistics and clinical details.


The crying baby--why colic?

The crying baby--why colic? All babies cry, but the mother unable to satisfy her infant's distress may experience doubts as to her own mothering ability. Yet 'colic' is often used to explain away many problems of the infant. But to accept such a diagnosis denies mother and infant help at this difficult time.


Gastrointestinal pitfalls.

Gastrointestinal pitfalls. Gastrointestinal symptoms account for 15 to 30 per cent of patients presenting to first contact doctors. The disorders causing these are many and varied--some are rare but most are common. While a considerable depth of knowledge is necessary to suspect, diagnose and treat the rarer diseases, it is the common conditions which constitute the major problems in everyday practice. These problems usually result from inadequate clinical assessment, from a lack of logical thought, from incorrect teaching in undergraduate years and from an uncritical application of therapeutic methods which are not based on scientific fact.


Pitfalls in geriatric medicine.

Pitfalls in geriatric medicine. Physiological deterioration complicates presentation of pathological processes in old age. Symptomatology is often misleading or absent, and handling of therapeutic substances complicated by poor excretion. It is important to realize that requirements change, and there must be flexibility of ideas of management of the aged.


Phenistix in screening.

Phenistix in screening. Screening procedures have achieved notoriety in recent years because of their ability to detect diseases in their early phases and also because of their expense. This paper describes a little-known but simple urine screening test which, if used judiciously, may help with diagnosis and treatment, and yet remain relatively inexpensive.


Primary prevention in coronary heart disease: the role of an integrated medical, physical and psychological programme in a coronary prone population. Coronary heart disease is a disease of epidemic proportions in our modern affluent society. Primary prevention by way of a multifrontal programme appears to offer the most effective and logical approcah to combating this disease. Effective implementation of this approach requires patients to undergo a comprehensive assessment. This establishes accurate coronary risk profiles, identifies AT RISK patients, and is the basis for planning a sound intervention programme.


The principles of antenatal care.

The principles of antenatal care. Good obstetric care begins with good antenatal care. The aims of antenatal care are no different from the general aims of obstetrics; namely, to produce a healthy baby, which is breast-fed by its healthy mother.


Assessment of foetal welfare.

Assessment of foetal welfare. While the reduction in maternal and perinatal mortality remains a constant goal, the emphasis in modern obstetrics has shifted towards the assessment of foetal welfare in utero. However, if the clinician is to avoid ultimate confusion, he must temper the information which may be obtained from the numerous tests and techniques available with shrewd clinical judgement. In addition, in the current climate of economic audit, he must consider the cost of the investigations in pure monetary terms.


Antenatal care: selection of the high risk patient. Despite the best antenatal care, complications may arise during the course of any pregnancy, labour or puerperium. Some groups of women are more likely to develop complications. A method of detecting these high risk patients is discussed.


The treatment of hypertension in pregnancy. Hypertensive disease in pregnancy remains a major cause of maternal and perinatal morbidity and mortality. Control of maternal hypertension with antihypertensive therapy improves maternal and foetal outcome. If the blood pressure is elevated in early pregnancy, complications are more likely to occur to both mother and foetus, and the outcome may not be favourable. In labour the threat of severe pre-eclampsia or eclampsia is a constant hazard.


A survey of attitudes of obstetric patients to a new-old concept of postnatal care. One hundred and thirty six mothers who were patients in a low dependency postnatal maternity unit were surveyed to assess their attitudes to this kind of care, and whether they preferred it to the more traditional acute care maternity unit. Their confidence in caring for their babies was also assessed. A three month follow-up study sought a retrospective opinion of the unit and measured the incidence of breast feeding. The findings indicated an overwhelming support for this kind of unit.


The use of drugs in pregnancy and labour. The possibility of harmful effects from drug therapy during pregnancy should be constantly before the clinican. The ability of drugs to pass from mother to babe through the placenta must be remembered as errors in the administration of drugs during pregnancy can have disastrous consequences for the mother and/or baby.


Student's viewpoint. The response of patients to students observing general practice. Medical courses in Australia currently are encouraging students to observe general practice by way of short periods of attachment. The figures indicate that a significant proportion of the patients in the practice are going to be concerned about this, even though the exposure is very necessary. This article deals with the way that the 'three man consultation' can be fashioned in order to minimize discomfort of the patient, or unnecessary inhibition of the learning process for the student.


Refresher course for general practitioner obstetricians: report of a survey on needs and expectations. A survey of 52 general practitioner obstetricians attending a refresher course was carried out, the aims of which were to assess their motivation for attending, their expections of the course, and whether the course fulfilled these expectations. The main motivations for attending were interest and preparation for the Dip Obst RCOG examination. The main expectations were to be acquainted with current developments and to have tuition in practical procedures. The general practitioner obstetricians were generally satisfied with the course; however, they would have preferred a greater emphasis on informal tutorials rather than formal lectures, and practical procedures rather than recent advances in physiology and neonatology.


The necessity for information on medical manpower needs in Australia and its attainment. Authorities of all descriptions have been shown to require reasonably accurate ongoing statistics on medical manpower so they can make satisfactory plans and arrangements for the future. It is submitted that this information is no less important for medical graduates in planning their own personal future careers. Methods of obtaining this statistical information have been reviewed, and recommendations made to support propositions already suggested for providing the information and resolving the problems both personal and national.


Duodenal ulcer.

Duodenal ulcer. Duodenal ulcer is a common disease which places heavy demands on health care costs. The aetiology is unknown, but its pathogenesis is related to acid secretion. The characteristic symptom is chronic epigastric pain which precedes meals, occurs one to three hours after food, and one to two hours after retiring. The pain is relieved by food or antacids. Barium meal remains the prime investigation, but flexible endoscopy allows accurate visualization of the ulcer particularly in a scarred deformed duodenum. Complications include haemorrhage, perforation and obstruction. Time-honoured therapy including diet, antacids and anticholinergics simply relieves pain, whilst newer drugs (Tagamet, De-Nol, and Duogastrone) are effective in healing the ulcer. Surgery is indicated for complications or inadequately relieved pain.


Patients, doctors and medical education. There is an increasing interpersonal distance between doctors and patients which is adversely affecting the quality of medical care. Solutions to the problem have been sought in the training of doctors, but these may not be effective until it is possible to undertake some mutual education of doctors and patients. Ways in which this could be done are discussed.


Response to bidirectional and reverse selection for mating behavior in Japanese quail Coturnix coturnix japonica. Reported is a genetic analysis of mating behavior in male Japanese quail. Data were obtained from replicated experiments involving 12 generations of divergent selection for high and low cumulative number of completed matings (CNCM). No trait measured in the randombred control population changed significantly over time. Asymmetrical responses between the divergent lines were observed during various phases of selection. Reversed selection showed that additive genetic variance remains in the high lines. Small and unimportant were drift and error variances. Genetic and phenotypic relationships between CNCM and body weight were small but positive, while those between CNCM and relative aggressiveness were positive and intermediate. Also positive and intermediate were the correlations between CNCM and cloacal gland size.


Nonlinear modeling of multistable perception. Multistable figures show that the stimulus-percept relation is not a single valued function. We therefore propose a tentative nonlinear model on the hypothesis that the graph of this relation is the equilibrium set of a dynamic system. For simplicity and to obtain testable predictions, we consider a system whose bifurcations are gradient-like and thus generically described by the elementary catastrophes. We motivate this general model, and then show how, in conjunction with the principle of minimal singularity, it implies cusp catastrophe geometry in a specific perceptual example. Indeed, we argue for canonical cusp geometry in this case. The model incorporates naturally certain observed features of multistable perception, such as hysteresis and bias effects. Despite being a continuum model it is naturally compatible with the subjective dichotomy of bistable perception. The model makes testable predictions which may easily be extended to other specific examples of multistable perception.


Analysis of mechanisms regulating the expression of parental alleles at the GPD locus in mule erythrocytes. Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) was examined by 13% starch gel electrophoresis in 74 mules (42 females and 32 males), 35 donkeys, and ten horses. The quantitative expression of the parental alleles at the Gpd locus varies greatly in female mules from the hemizygous expression of the maternal allele to that of the paternal. The data obtained indicate that the X chromosomes are randomly inactivated in females mules. No selective advantage of a cell population with a maternally (or paternally) derived X active was found in female mule erythrocytes. It is suggested that the phenotypic variability in the expression of the parental Gpd alleles is related to the random proportions established between cells having either a maternal or paternal X active in an initiator (stem) cell group giving rise to erythroid tissue. Initiator cell numbers estimated for erythroid tissue (six or seven) are close to those reported for human females and intergeneric fox hybrids. These numbers may vary depending on the duration of the time of determination and the division rate of initiator cells at determination.


Screening of inbred rat strains for electrophoretic protein polymorphisms. Nineteen inbred strains of the laboratory rat (Rattus norvegicus) were investigated for genetic differences by starch and agarose gel electrophoretic techniques. For six out of 21 loci, interstrain differences were observed: Tf, 6PGD, Es-1, Es-4, Es-5, and Svp. The variants are briefly described and the allelic distributions are tabulated. The 6GPD locus was found to be linked neither to the major histocompatibility gene region nor to the coat color genes c, a, h.


Genetic regulation of liver alcohol dehydrogenase in Peromyscus. Data from genetic crosses of Peromyscus maniculatus and P. polionotus suggests that electrophoretic variants of liver alcohol dehydrogenase are coded by alleles at a single locus. These alleles, designated AdhF, AdhS, and AdhN, determine, respectively, the fast, slow, and not detectable (null) ADH electrophoretic phenotype. Heterozygotes (AdhF/AdhS) exhibit three bands on zymograms, suggesting a dimeric subunit structure for the enzyme. However, AdhF/AdhN and AdhS/AdhN animals exhibit a single band, suggesting that the AdhN allele does not produce a polypeptide subunit capable of dimerizing into an active molecule. Fast and slow electrophoretic phenotypes exhibit multiple bands which can be converted into single major fast and slow bands, respectively, upon treatment with oxidized or reduced NAD. Addition of NAD also stabilizes both the fast and slow enzyme to heat inactivation at 60 C for at least 30 min.


Assignment of the gene for dipeptidase 2 to Mus musculus chromosome 18 by somatic cell hybridization. Evidence is presented for the assignment of the gene for dipeptidase 2 to Mus musculus chromosome 18 by synteny testing and karyotypic analysis of Chinese hamster x mouse somatic cell hybrid clones. DIP-2 and chromosome 18 were expressed concordantly in 24/24 clones examined (ten primary clones and 14 secondary clones). Synteny testing indicated that DIP-2 was not expressed concordantly with the expression of any marker enzymes.


Survey of isoenzymes in the snail Cepaea nemoralis using different buffer/gel systems in polyacrylamide disc gel electrophoresis: validity of comparisons and effect of "nothing dehydrogenase" activity. An investigation into isoenzymic analysis using four different buffer/gel systems was carried out. Fourteen different isoenzyme systems were surveyed on each buffer/gel system. It is shown that comparable results are not obtained between different systems. Previous workers in Cepaea nemoralis have used different buffer/gel systems from one another. Alkaline phosphatase and acid phosphatase and certain lactate and malate dehydrogenases are shown to behave similarly in three different systems. It is tentatively suggested that these isoenzymes may be genetically identical. "Nothing dehydrogenase" activity is demonstrated in gels stained for other dehydrogenases. It is suggested that nothing dehydrogenase activity may be attributable to glutamate or malate dehydrogenase.


Identification and linkage relationships of three hexokinase genes in Aedes aegypti. Four regions of hexokinase activity are detected by starch gel electrophoresis of adult Aedes aegypti. Three of the regions, Hk-2, Hk-3, and Hk-4, are produced by three tightly linked loci, located on the third chromosome 7.25 map units from the locus fuzzy. The three loci show developmental differences as well as differences in substrate specificity.


Genetic bases for protein polymorphism in Fundulus heteroclitus (L.).I. Lactate dehydrogenase (Ldh-B), malate dehydrogenase (Mdh-A), glucosephosphate isomerase (Gpi-B), and phosphoglucomutase (Pgm-A). Electrophoretic analysis has shown populations of F. heteroclitus to possess variants at four enzyme-coding loci: Ldh-B, Mdh-A, Gpi-B, and Pgm-A. Based on the phenotypic distribution in the F1 generation, each variant segregates as an autosomally inherited codominant allele. A pairwise comparison of the expected phenotypic classes among these loci showed no evidence of strong linkage; however, weak linkage could not be ruled out. Despite the considerable genetic divergence of populations from the geographical extremes of this species, offspring resulting from crosses between individuals from these localities show viabilities similar to those found for crosses of local populations.


Biochemical genetics of Fundulus heterolitus (L.). I. Temporal and spatial variation in gene frequencies of Ldh-B, Mdh-A, Gpi-B, and Pgm-A. Natural populations of Fundulus heteroclitus show extensive spatial variation in gene frequencies at four unlinked polymorphic loci. Large clinal changes in gene frequencies were found for Ldh-B, Mdh-A, and Gpi-B, whereas the spatial variation for the Pgm-B locus was small. Since the geographical area over which these clines are found is characterized by a steep thermal gradient, the clines in gene frequency are correlated with a directional change in mean water temperature. Maximum gene diversity of these four loci was correlated with annual fluctuations in water temperature. Temporal stability of the allelic frequencies was established for a 2--4 year period.


Heterosis in a wild strain of Drosophila polymorpha with a lethal closely linked to the major esterase locus. A laboratory population derived from a single wild inseminated female has a lethal so closely linked to the major esterase locus that in 3 years of observations no crossover products have been detected. Linkage with a chromosome inversion was excluded by cytological analysis. The heterozygotes are superior to the homozygotes in egg-adult viability, egg-laying rate, and longevity. Electrophoretic analysis of larvae, pupae, and 2-h-old adults shows that the specific phase for the lethal effect in homozygotes is the pupal stage.


The susceptibility of muscle phosphorylases a and b to digestion by a neutral proteinase from rat intestinal muscle. Comparison with the effects produced by pancreatic trypsin and chymotrypsin. 1. Phosphorylase b was inactivated three times more rapidly than phosphorylase a by a neutral, trypsin-like proteinase from rat intestinal muscle. Digestion of phosphorylase a produced a modified form which was deactivated by AMP. Removal of the pyridoxal phosphate cofactor increased the rate of inactivation of the b form by about 3-fold but the subceptibility of apophosphorylase a was no different from the holo form. 2. The extent of proteolysis of both holoenzyme forms, as guaged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, was limited and similar digestion patterns were obtained in both cases. 3. With (32)P-labelled phosphorylase a as substrate, the initial event in the inactivation was the release of a trichloroacetic acid-soluble peptide from the N-terminus of the enzyme, leaving the original 100000 subunit form essentially unchanged. Subsequent proteolysis was restricted, producing derivatives of mol.wt. 85000, 70000 and 65000, none of which contained any radioactive label. 4. By treatment of inactivated phosphorylase b with carboxypeptidase B, it was shown that the intestinal muscle proteinase had cleaved approximately 3 -Lys-X and 3 -Arg-X bonds in the polypeptide. 5. The protective effects of various allosteric modulators of phosphorylase on the inactivation of the a and b forms were generally in agreement with the known roles of the modifiers. Glucose increased the susceptibility of phosphorylase a. 6. Inactivation of phosphorylase b by trypsin and chymotrypsin also resulted in limited proteolysis but, in both cases, the digestion patterns obtained on sodium dodecyl sulphate/polyacrylamide gels were different from each other and from the pattern obtained with the intestinal muscle proteinase. 7. Inactivation of phosphorylase b by the muscle proteinase is about 100 times more rapid than the effects produced by trypsin or chymotrypsin when the activities are compared on an equimolar basis. 8. Consideration is given to regulation of the rate of enzyme degradation intracellularly by modulation of the conformation and susceptibility of the enzyme via factors such as covalent modification, allosteric ligands and state of aggregation.


Circular-dichroic studies on the conformational behaviour of troponin and tropomyosin from bovine cardiac muscle. Bovine cardiac troponin is similar to rabbit skeletal troponin with respect to secondary structure, amino acid composition and molecular weight of the subunits, but differs slightly with respect to biological activity and surface charges of the subunits. Previous circular-dichroic studies of the subunits and recombination of subunits have indicated significant Ca2+-induced delocalized conformational changes. Present studies of the native troponin complex are not in accord with such changes. Furthermore the formation of the troponin-tropomyosin complex in vitro results in no delocalized conformational changes, nor does it sensitize troponin to Ca2+-induced changes. It is suggested that the troponin complex cannot be dissociated into subunits without significant and irreversible conformational perturbation.


Genetic variants involving the major membrane sialoglycoprotein of human erythrocytes. Studies on erythrocytes of type Mk, Miltenberger class V and Mg. 1. Membranes from erythrocytes heterozygous for the Mk and Miltenberger Class V (Mi.V) condition and membranes from erythrocytes homozygous for the Mg condition were studied by polyacrylamide-gel electrophoresis by using the periodate/Schiff stain binding of radioiodinated lectins and labelling with lactoperoxidase. 2. Both the Mk and Mi.V conditions are associated with a decreased content of the major blood-group-MN-active sialoglycoprotein. 3. An unusual blood-group-M-active membrane component was found in Mi.V cells of appropriate genotype. No comparably component was found in Mk erythrocytes. 4. The Mg antigen appears to result from a modification of the MN-active sialoglycoprotein found in normal cells. Our results suggest that the Mg sialoglycoprotein contains fewer sialotetrasaccharides than does the normal sialglycoprotein. This may result from changes in the amino acid sequence of the protein. 5. The results are discussed in relation to differences in the antigenic properties of Mk, Mi.V and Mg cells and their possible influence on the structure of the surface of each of these cells.


Isolation of heavy satellite deoxyribonucleic acid from sea-urchin spermatozoa. Two different methods were used to isolate high-molecular-weight heavy satellite DNA from the spermatozoa of the sea-urchin Lytechinus variegratus. Purification of satellite rDNA (ribosomal DNA) by selective denaturation of the spermatozoal DNA followed by a separation of the native and denatured DNA in an aqueous mixture of poly(ethylene glycol)/dextran is affected by the molecular weight of the spermatozoal DNA. Enrichment of satellite rDNA by selective precipitation of main-band DNA by poly-L-lysine is cumbersome but more suitable.


Differential effects of non-ionic detergents on microsomal and sarcolemmal adenylate cyclase in cardiac muscle. 1. About 4 and 23% of the homogenate adenylate cyclase activity was recovered in the microsomal and sarcolemmal fractions isolated from guinea-pig heart ventricles. 2. Cardiac microsomal adenylate cyclase activity [basal as well as p[NH]ppG (guanyl-5'-yl imidodiphosphate)- and NaF-stimulated] was increased over 2-fold in the presence of Lubrol-PX (0.01-0.1%). 3. The sarcolemmal enzyme, however, showed concentration-dependent inhibition caused by the detergent under all assay conditions, except when p[NH]ppG was included in the assay. In the latter case, the detergent (0.01-0.02%) caused a modest increase (30-45%) in enzyme activity. 4. Another non-ionic detergent, Triton X-100, also stimulated the microsomal cyclase and inhibited the sarcolemmal enzyme. 5. With either membrane fraction, Lubrol-PX solubilized the enzyme when the detergent/membrane protein ratio was 2.5 (mumol of detergent/mg of protein). 6. The findings with homogenate and a washed particulate fraction resembled those obtained with sarcolemma, and those with isolated sarcoplasmic reticulum resembled those with microsomal preparations. 7. p[NH]ppG, and to some extent NaF, protected the detergent-induced inactivation of the enzyme observed at higher detergent concentrations (0.5% Lubrol-PX and 0.05-0.5% Triton X-100). 8. In the absence of detergents, p[NH]ppG increased the basal enzyme activity about 2-fold in microsomal fractions, but did not appreciably stimulate the sarcolemmal enzyme. Isoproterenol, on the other hand, increased the sarcolemmal enzyme activity (>2-fold) in the presence of p[NH]ppG and caused only moderate stimulation (31%) of the microsomal enzyme under these conditions. 9. These findings support the view that, although the bulk of adenylate cyclase resides in heart sarcolemma (plasma membrane), the microsomal activity cannot be accounted for solely by contamination of the microsomal fraction with sarcolemma, as has been suggested by others [Besch, Jones & Watanabe (1976) Circ. Res.39, 586-595; Engelhard, Plut & Storm (1976) Biochim. Biophys. Acta451, 48-61]. Further, the results of this study show that cardiac sarcoplasmic-reticulum membranes possess this enzyme.


Release of two thioesterase domains from fatty acid synthetase by limited digestion with trypsin. Limited digestion, with trypsin, of the fatty acid synthetase from rat mammary gland releases an enzymically active thioesterase component that, under denaturing conditions, consists of two major species of mol.wts. 35000 and 17500 and a minor species, mol.wt. 15,000. The 17500- and 150000-mol.wt. species are shown to originate from the 35000-mol.wt. species as a result of nicking by trypsin. The nicked polypeptides are enzymically active. The fatty acid synthetase is inhibited by [1,3-14C]di-isopropyl phosphorofluoridate, which is shown to bind to, and inactivate, two thioesterase active sites. When the [1,3-14C]di-isopropyl phosphate-labelled fatty acid synthetase is subjected to limited digestion with trypsin, all of the radioactivity is recovered in the isolated thioesterase component, i.e. in the 35000-mol.wt. polypeptide and its nicked products. Since the isolated thioesterase is shown to bind only one di-isopropyl phosphate residue per 35000-mol.wt. polypeptide, we conclude that the fatty acid synthetase has two thioesterase domains, both of which are removed by limited trypsin treatment.


The specificity of the interaction of bovine pancreatic ribonuclease A with natural and halogenated purine nucleotides. The interaction between bovine pancreatic ribonuclease A (EC 3.1.4.22) and the purine nucleotides AMP, GMP, 6-chloropurine 5'-ribonucleotide and 8-bromoadenosine 5'-monophosphate was studied by u.v. difference spectroscopy. The stoicheiometry of the binding of the halogenated nucleotides to the enzyme shows a 1:1 ratio, as for the natural ones. The binding constants, Ka, for all four nucleotides at pH 5.5 were determined. They are within the same order of magnitude, though the nucleotides with a 6-amino group show a stronger interaction. The magnitude of the binding shows a reciprocal dependence on the ionic strength, which indicates an electrostatic interaction between ligand and enzyme. Finally, solvent-perturbation experiments show that all four nucleotides bind to the enzyme in a partially hydrophobic region. It is concluded that both halogenated and natural purine ribonucleotides interact in a similar manner with the enzyme molecule. The special synthesis and identification of 6-chloropurine 5'-ribonucleotide are discussed extensively. It is concluded that both halogenated and natural purine ribonucleotides interact in a similar manner with the enzyme molecule and thus the halogenated analogues are potential reagents for the affinity labelling of the purine-binding site.


Studies on ram acrosin. Activation of proacrosin accompanying the isolation of acrosin from spermatozoa, and purification of the enzyme by affinity chromatography. 1. A previously described, freeze-dried, partially purified ram acrosin preparation was fractionated on a column of Sepharose linked to the acrosin inhibitor p-(p'-aminophenoxypropoxy)benzamidine. Two acrosin fractions were obtained. 2. beta-Acrosin was homogeneous, quite stable at low pH and very stable when freeze-dried. Its molecular weight is about 38000, and it contains about six sugar residues per molecule, but no sialic acid. psi-Acrosin consisted of at least three unstable forms of acrosin. 3. When the entire purification process, starting from collection of semen, was carried out as rapidly as possible, the yield of beta-acrosin was increased and very little psi-acrosin was obtained. 4. In fresh ram semen the acrosin is present as the intra-acrosomal zymogen, proacrosin. After its extraction from spermatozoa autoproteolytic reactions convert proacrosin into beta-acrosin; psi-acrosin appears to be breakdown products of beta-acrosin. 5. When beta-acrosin was passed through a column of Sepharose linked to the non-inhibitory deamidinated analogue of the inhibitor it behaved as a hydrophobic protein. This is consistent with our view that acrosin (as zymogen) occurs in spermatozoa as a membrane-bound protein. 6. Success in the isolation of pure acrosin in high yield calls for an affinity adsorbent with the appropriate subsidiary hydrophobic properties.


Isolation of the C-fragment and C'-fragment of lipotropin from pig pituitary and C-fragment from brain. Three novel peptides derived from lipotropin, the C-Fragment (residues 61-91), C'-Fragment (61-87) and N-Fragment (1-38), were isolated from pig pituitary, and the C-Fragment was shown to be present in brain. The experimental procedures developed for their isolation are described. The formation of each of the fragments involves enzymic cleavage of lipotropin at consecutive basic residues, with specificity identical with that involved in the activation of known prohormones. In brain assays C-Fragment exhibits a range of biological activities related to its ability to act as an inhibitory neurotransmitter.


beta-Bungarotoxin. Separation of two discrete proteins with different synaptic actions. beta-Bungarotoxin, a specific presynaptic blocking agent, was prepared in two stages from the crude venom of Bungarus multicinctus by ion-exchange chromatography on the weakly acidic ion exchanger, CM-Sephadex, and on the strongly acidic ion exchanger, sulphopropyl-Sephadex. By these procedures it was purified to a single protein, which was shown by reduction to contain two polypeptide chains with mol.wts. of less than 15000. During purification of beta-bungarotoxin three other proteins were isolated. Two of these proteins have similar molecular weights, subunit structure and physiological properties to the major protein component. This latter is referred to as beta-bungarotoxin, since it has the same physiological properties as those described for unpurified beta-bungarotoxin by other workers. The first protein has very different physiological effects and biochemical properties from beta-bungarotoxin. This protein has a single class of polypeptide chains with an apparent molecular weight that is lower than the main beta-bungarotoxin protein, and appears to block synaptic transmission by a predominantly postsynaptic effect. It has been suggested [Oberg & Kelly (1976) J. Neurobiol. 7, 129-141] that the action of beta-bungarotoxin depends on its phospholipase A activity; however, in this preparation of the toxin less than 50 muunits of phospholipase A activity were detected (1 unit of activity is the amount of enzyme forming 1 mumol of L-alpha-phosphatidylcholine/min per mg of protein).


beta-Bungarotoxin. The binding of [3H]pyridoxylated beta-bungarotoxin to a high-molecular-weight protein receptor. beta-Bungarotoxin was labelled with pyridoxal 5'-phosphate (incorporating 3H). The kinetics of beta-bungarotoxin binding to several tissue subfragments of nervous tissue was studied. The dissociation constant of 3H-pyridoxylated beta-bungarotoxin in this reaction was 0.21-0.37 micron and that of unlabelled beta-bungarotoxin was 25 nM. Hill [(1910) J. Physiol. (London) 40, iv-vii] and Scatchard [(1949) Ann. N.Y. Acad. Sci. 51, 660-672] analyses demonstrated no co-operativity of binding and only a single class of receptor sites, consistent with a bimolecular association of beta-bungarotoxin and its receptor. The iodinated toxin was physiologically inactive. Toxin was bound in non-specific unsaturable fashion by glass and/or plastic. This low-affinity binding was corrected by addition of bovine serum albumin to a final concentration of 30 mg/ml. A soluble protein receptor of beta-bungarotoxin was isolated and the mol.wt. is approx. 200000.


Isolation and characterization of the subunits of bovine follitropin. Highly purified bovine follitropin was dissociated into its alpha- and beta-subunits after treatment with 1 M-propionic acid. The dissociated subunits were fractionated by chromatography on DEAE-cellulose and further purified by gel filtration on Sephadex G-100. The isolated alpha- and beta-subunits were biologically inactive, but their recombinants regenerated 80% of the follitropin activity. The alpha-subunit of bovine follitropin recombined with the beta-subunits of bovine lutropin and thyrotropin to regenerate 70% of lutropin and 50% of thyrotropin activities respectively. The beta-subunit of bovine follitropin recombined with the alpha-subunit of either bovine lutropin or thyrotropin to regenerate about 75% of follitropin activity. Recombinations were monitored by specific radioligand-receptor assays and polyacrylamide-gel electrophoresis. The elution volumes of the alpha- and beta-subunits of bovine follitropin after gel filtration on Sephadex G-100 were almost identical. The amino acid composition of bovine follitropin-alpha was low in histidine, arginine, isoleucine and leucine, but relatively high in lysine, threonine and glutamic acid. The bovine follitropin-beta contained one methionine residue and low amounts of histidine and phenylalanine, but relatively high in aspartic acid, threonine and glutamic acid. The N-terminal residues of the alpha- and beta-subunits of bovine follitropin were identified to be phenylalanine and glycine respectively.