[Population genetics of the inhabitants of Northern European USSR. II. Blood group distribution and antropogenetic characteristics in 6 villages in Archangel Oblast].

The paper deals with the distribution of genetic markers (systems ABO, MN, Rh (D), Hp, PTC) and a number of demographic (folding of arms, hand clasping, tongue rolling, right- and left-handedness, of the type of ear lobe, of the types of dermatoglyphic patterns) in the inhabitants of 6 villages in the Mezen District of the Archangelsk Region of the RSFSR (river Peosa basin). The data presented in this work were obtained in the course of examination of over 800 persons. Differences in the interpretation of the results of generally adopted methods of statistical analysis of samples from small populations are discussed. Among the systems analysed in one third of all the cases there was a statistically significant deviation from Hardy-Weinberg's ratios. For the MN blood groups and haptoglobins this was caused by the excess of heterozygotes. The test of Hardy--Weinberg's ratios at the level of two-loci phenotypes revealed no statistically significant deviations either in separate villages or in all the villages taken together. The analysis of heterogeneity with respect to markers inherited according to Mendel's law revealed statistically significant differences between villages in all the systems except haptoglobins. A considerable heterogeneity in the distribution of family names, the frequencies of some of them varying from village to village from 0 to 90%. Statistically significant differences between villages were shown for all the anthropogenetic characters except arm folding, hand clasping and right-left-handedness. Considering the uniformity of the environmental pressure in the region examined, the heterogeneity of the population studied is apparently associated with a random genetic differentiation (genetic drift) and, possibly, with the effect of the progenitor.


[Complex study of human cell strains with karyotype anomalies. II. Mitotic cycle parameters].

The object of this investigation were the parameters of the mitotic cycle in 14 fibroblasts-like cell strains with chromosome aberrations obtained from skin biopsies of patients and from spontaneous human abortuses. In two strains of embryonal origin (trisomic for chromosome and monosomic for chromosome 21) increased duration of stage G2 of the cell cycle accompanied by a shorter period of DNA synthesis was observed. In the other 5 strains of embryonal origin (two strains trisomic for chromosome 7, strains trisomic for chromosome 9, trisomic for chromosome 14 and triploid strains) no deviations from the normal duration of the stages of the cell cycle were observed. Two types of changes of the mitotic cycle parameters were observed in the cell strains obtained from patients with chromosome aberrations. A considerably prolonged G2 stage was observed in two strains obtained from patients affected by Down's syndrome. Three strains with the karyotypes 47, XXX, 47 XY+18 and 46, XX, 5p-were characterized by a complex of features typical of the strains of embryonal origin. A considerable decrease of the stage G2 duration was observed in these strains. In the strains obtained from a proband with Kleinfelter's syndrome and from a patient with the karyotype 46XX no deviations in the parameters of the cell cycle were observed.


Tumor-like pulmonary manifestations of congestive heart failure.

Two cases of "phantom tumors" of the right lung on elderly subjects with congestive heart failure are described. One presented a picture of patchy bronchopneumonia, whereas the second had been diagnosed as a lung carcinoma 1 month before hospitalization because of a round lesion. In both cases the radiological picture cleared up within a few days following rest, diuresis and digitalization. The possibility of congestive heart failure as a cause for development of circumscribed pulmonary opacities should always be kept in mind.


[The inquinal-flap-anatomical studies of the axial vessels and their course].

In plastic surgery of the hand the groin-flap is preferred to other axial pedicled flaps for practical and cosmetic reasons. This groin-flap described by McGREGOR and JACKSON 1972 is based on the superficial circumflex iliac artery (Arteria circumflexa ilium superficialis = "A. cis."). Details concerning the origin and course of the A. cis. may best be described with reference to the two osseous prominences that can be palpated through the skin of the inguinal region; the anterior superior iliac spine (S) and the pubic tubercle (T) (Fig. 1).


[Effects of beta-phenylethylamine derivatives on the central nervous system. (5) The effect of intracerebral administration of tyramine on head twitching in mice pre-treated with isocarboxazid].

Effects of drugs on head-twitches induced by tyramine (Ty) in isocarboxazide (Iso) pretreated mice were studied and the following results obtained: 1) In beta-phenylethylamine derivatives, p-hydroxyamphetamine in non-treated and Iso-pretreated mice and Ty in Iso-pretreated mice produced head-twitches. 2) Injection of 5-HTP (i.c. and i.p.) into mice induced head-twitches. 3) Although head-twitches were not induced by a low dose of 5-HTP (20 mg/kg, i.p.), in Iso pretreated mice, the number of headtwitches increased markedly in the Iso-Ty treated group when Ty was injected i.c. in Iso+5-HTP (20 mg/kg) pretreated mice. 4) When Iso-Ty was injected into alpha-methyl-p-tyrosine pretreated mice, the number of head-twitches increased markedly compared with Iso-Ty treated group. 5) When Iso-Ty was injected into mice sustained with p-chlorophenylalanine, the number of head-twitches decreased markedly compared with the Iso-Ty treated group. 6) The number of head-twitches decreased markedly when Iso-Ty was injected into dimetotiazine pretreated mice, however the administration of Iso-Ty in haloperidol pretreated mice had no influence on head-twitches. 7) It is concluded that serotonin is the acting mediator in the head-twitch response.


A failure to improve radiologists' performances in diagnosing pulmonary lesions by a computer-aided approach.

A traditional radiological evaluation of five lung diseases and their computer-aided diagnosis with Bayes' approach, were based on the plain chest film. Parameters of diagnostic performance for 12 radiologists, who made 1224 diagnoses by each method, were compared. Under the conditions of this study the use of a computer-aided method did not improve radiologists' performances independently of their diagnostic ability and experience.


[Three-stage method in lung scintigraphy: ventilation, diffusion and perfusion (author's transl)].

A combination of three stages--ventilation, "perfusion" and diffusion-- has proved to be the optimal method in the scientigraphic exmaination of the lung. 85mCrypton is preferred for ventilation studies compared with 133Xenon, in view of its more suitable radiation energy and lower solubility. In the pre and post-operative investigation of the lungs, ventilation estimations are essential, providing a more reliable perameter than "perfusion estimations". The results from "perfusion" measurements with MAA or microspheres frequently do not correspond with those obtained by 133Xenon. It is still debatable whether the use of MAA or microspheres provide perfusion values and it would be better at present to speak of MAA fixation results.


[Camera-cinematography of the heart (author's transl)].

By "camera-cinematography" of the heart, we mean an isotope method which permits detailed observation of cardiac mechanics without the use of a catheter. All that is necessary is an intravenous injection of 10 to 15 mCi 99mTc human serum albumen followed after ten minutes by a five to ten minute period of observation with a scintilation camera. At this time the isotope has become distributed in the blood. Variations in the precordial impulses correspond with intra-cardiac changes of blood volume during a cardiac cycle. Analysis of the R-wave provides adequate information of cyclical volume changes in limited portions of the heart. This is achieved by a monitor with a pseudo-3-dimensional display; contraction and relaxation of the myocardium can be shown for any chosen longitudinal or horizontal diameter of the heart. Our programme allows simultaneous presentation of the movement of any point on the myocardium as a time-activity curve. The method is recommended as an addition to chest radiography, heart screening or cardiac kymography before carrying out cardiac catheterisation.


[Estimation of ventricular volume derived from three transverse diameters and the longitudinal axis, compared with an area-longitudinal axis method (author's transl)].

The difficulty of automatic volume estimations of the left ventricle from cine-ventriculography lies in the accurate definition of the ventricular contour during the whole of the cardiac cycle. On the other hand, automatic determination of the long axis of the ventricle, and of three transverse diameters, is feasible. An attempt was therefore made to see whether accurate ventricular volume estimations could be obtained from these measurements. Two different geometrical models were examined: a) A complete rotational ellipsoid b) A half rotational ellipsoid. Examination of ten cine-ventriculograms (totalling 546 frames) has shown that the ventricular volume can be determined with an adequate accuracy by this method. The half ellipsoid model produced better mean results than the full ellipsoid. Its mean deviation from the area-long axis method was only minus 1.2%, that of the complete ellipsoid was minus 3.3%.


[The accuracy of surface kymography following myocardial infarcts, with special reference of cardiac aneurysms (author's transl)].

Surface kymography in three planes were performed in 180 patients following myocardial infarcts, and these were compared with the results of coronary angiography and selective laevocardiography. Kymography performed for the diagnosis of cardiac aneurysms and myocardial scars is relatively accurate (53%), as shown by a comparison with the laevocardiograms. Of the aneurysms demonstrated by laevocardiography in the left ventricle (31), it was possible to show 22 (71%) kymographically. In order to achieve these results, it is necessary to examine at least three marginal contours of the left ventricle by kymography (left heart border, anterior and posterior wall). The routine use of kymography before employing invasive techniques provides useful information regarding the optimal plane of the laevocardiogram. Furthermore, it indicates the presence of myocardial disease and the need for further investigation.


[Methods of functional scintigraphy of the heart: the effect of the radiopharmaceutical agents (author's transl)].

Functional scintigrams of the heart were performed in 63 patients using different injection techniques and two radiopharmaceuticals (99mTc-pertechnitate and 99mTc-human serum albumen). A comparison of the results shows that injection of 99mTc-human serum albumen into the femoral vein gave the best results. Injection of the tracer into the femoral vein causes less dilution of the bolus than the usual injection technique into the cubital vein. There is less recirculation of the indicator resulting in lower co-efficients of variation of the quantitative parameters. The choice of 99mTc-human serum albumen facilitates demarcation of the individual cardiac chambers.


[Aberrant pulmonary vessels from the abdominal aorta in children with congenital heart disease (author's transl)].

Ten children are described in whom aberrant pulmonary vessels arising from the abdominal aorta were found in the course of cardiac investigations. In five, sequestrated lung, as described Pryce, was demonstrated; in the others, these vessels were found incidentally without any demonstrable abnormality in the lung. Our findings indicate that one must distinguish between aortic pulmonary vessels with and without pulmonary sequestration during childhood. The need for deliberate opacification of the aorta is pointed out. This is also necessary in arriving at the indications for sergery. In the presence of congenital heart defects, these arterial vessels are found particularly in the presence of hypoplastic lungs and with the scimitar syndrome (3 cases).


[Arteriovenous aneurysm between the intercostal artery and subclavian vein in the presence of multiple arterial aneurysms (author's transl)].

An arteriovenous aneurysm of the fifth intercostal artery on the left, communicating with the left subclavian vein, is described. This has not been observed previously. It occurred in a 50-year old woman with multiple arterial aneurysms and stenosing aortic sclerosis.


[The collateral circulation for occlusion of the three unpaired abdominal arteries (author's transl)].

A fifty-two year old patient had only a short period of abdominal angina, despite occlusion of all three unpaired abdominal aortic branches. An extensive collateral system provided the circulation to the abdominal organs: intercostal arteries and adrenal vessels through the inferior phrenic artery for the coeliac trunk; arteries from the left iliac for the inferior mesenteric artery and through Riolan's arc (type II) for the superior mesenteric artery. Lumbar vessels provided a supply to the proximal territory of the superior mesenteric artery. In addition, it was possible to demonstrate connections between several lumbar arteries; several of these were also occluded proximally.


[Neurological complications of abdominal angiography (author's transl)].

Two cases of a cord trans-section syndrome resulting from contrast damage to the spinal medulla were observed amongst 4,000 abdominal angiograms (0.05%). The anatomical basis, causes and means for avoiding this serious complication of abdominal catheter angiography, are discussed.


[Investigations of flow through end arteries in diseases of digital vessels using radio-active tracers (arterial occlusive disease, acrosclerosis and sclerodermia) (author's transl)].

Using 113mIndium chloride and an Anger scintilation camera, flow rates were measured and recorded in defined distal parts of the hand. The method is a useful complement to previous diagnostic techniques and provides information regarding flow through end-arteries which cannot otherwise be obtained. Because of the low risk, even of intra-arterial injection of the tracer substance, isotope angiography can be used as a means of controlling operative and conservative treatment.


[The roentgen morphology of isolated tumourous pulmonary amyloidosis (author's transl)].

A patient with isolated tumourous pulmonary amyloidosis was seen and surgically treated in our clinic. The roentgen morphology of this extremely rare condition is described and the cases published in the literature are reviewed. Knowledge of this disease makes the radiological diagnosis easier and is of importance to the surgeon in planning treatment.


[On the reliable visualization of digital arteries as recorded by arteriography applying only local anesthesia and alcoholic drink (author's transl)].

Reliable visualization of arteries in hands, fingers, feet and toes largely depends on the tone of peripheral vessels. This can be lowered by general anesthesia but also under local anesthesia if local warming and oral Alcohol are added. Differential diagnosis between organic and functional disturbances of circulation is guaranteed in this way. Digital arteries can be well shown right down to the tips of fingers and toes.


[A comparison of the radiation dose from film and xeroradiography (author's transl)].

Using a LiF dosimeter, comparative measurements were carried out on film mammography and xeromammography on surface and exit dose to the breast and scatter at the level of the gonads. Exit dose at 200 to 330 mR was approximately the same for both methods; incident dose at 6,800 mR for film mammography was significant higher than for xeromammography at 3,800 mR (Mo tube) or 1, 200 mR (tungsten tube). Scatter at the level of the gonads for all three methods was between 4.4 and 12.8 mR. For xeroradiography of the knee joint, the radiation dose of 466 mR was approximately three times that for a film technique (160 mR).


[Optimal distances for direct radiographic magnification].

This paper deals with the theoretical basis for radiographic magnification. In particular, the relationship between focal size and optimal magnification for various systems is discussed. Maximal resolution was chosen as the criterion for best results. It has been shown that resolution (Lp-mm) can be improved by the reciprocal of the focal spot and for optimal magnification (see article) where f is focal spot size and AVBW is resolution of the imaging system.


[RODOC--a system for the documentation of radiographic diagnoses with electronic data processing (author's transl)].

A system for the documentation of radiographic diagnoses is described, based on the "documentation method for radiographic diagnosis" (Formmhold et al 1972) and on the diagnostic information system of the medical faculty of the University of Tübingen. The diagnostic indeces are dictated in relation to the findings and the diagnosis and fed on punched cards into a computer (IBM 1800). Various programmes provide patient-orientated diagnoses for clinical routine, as well as diagnoses-orientated lists of patients for demonstrations, teaching or research.


[The triangular iliac hyperostosis -- the sacro-iliac bony stress phenomenon. 1st part (terminology, definition, morphology) (author's transl)].

The first part of this article concerning the trianular iliac hyperostosis -- the former so-called osteitis condensans ilii -- deals with the proposed terminology. Tomographs of 40 patients were available. The x-ray morphology and the histology (2 necropsies) are described.


[Radiological aspects of the basal cell naevus syndrome (Gorlin-Goltz syndrome) (author's transl)].

The radiological features of the basal cell naevus syndrome (Gorling-Goltz syndrome) are described, based on four of our own cases and 105 collected from the literature. Multiple cysts in the lower or upper jaw are found in 92% and 35% respectively. Anomalies of ribs are present in 45%, calcification of the falx in 49% and a scoliosis of the spine in 32% of cases. In our four patients, multiple small cysts were found in the bones of the hands and of the arms. These changes have not been previously described.


[Angiographic evaluation of abnormal fracture repair (author's transl)].

Abnormal healing of fractures has been divided into three groups: delayed healing, reactive and non-reactive pseudoarthrosis. There are many transitions between these. Routine radiography can only classify these after their morphological appearance. Angiography is able to provide information regarding the vitality of major and minor fragments according to the type of para- and interfragment vascularisation; in some cases there may also be some neovascularity. The potential for union depends directly on the vascularisation of the surrounding muscles, of the subcutaneous tissues and of the skin. Vascular changes result in the formation of an autonomous circulation, independent dynamically of the vessels in the extremity and which can guarantee an increased saturation during healing by new bone formation. Angiography can provide an estimate of the likelihood of union and thereby provide a prognosis; it can also help to predict the fate of autotransplants and the strength of surgically reconstructed bone, since inadequate circulation may result in devitalisation of fragments.


[Broncho-vascular branching in the sub-segment (author's transl)].

The three pulmonary branching systems in the sub-segment have been studied by making casts. A comparison between them shows considerable differences between the vascular systems and the air passages. The bronchi show two types of branching: we can distinguish between irregular, dichotomous acute angled branching and predominantly regular dichotomous, wide-angled branching. The second type is often found in the bifurcations of large vessels and bronchi in the lung centre, where the lung parenchyma is made to fit into a confined space. Branching of the bronchi is very different from that of the vessels. The characteristic features of the latter are that the lateral branches are more numerous but smaller than the corresponding bronchi and show less contact with the lung periphery.


[Pulmonary findings in Wegener's granulomatosis (author's transl)].

Six patients with the rare condition of Wegener's granulomatosis showing pulmonary manifestations are described. Five patients died at an average age of 40 years; the average duration of their disease was 4.6 months. The pulmonary changes which can be demonstrated radiologically and pathologically are extremely variable. Differential diagnosis is made exceedingly difficult by the presence of necrotic cavities with variable changes in the walls, by miliary or linear infiltrates, round foci or changes resembling bronchopneumonia. In our experience there are no typical radiological changes in the lung which are diagnostic of Wegener's granulomatosis. Treatment has been improved by the use of cytotoxic agents and the necessary early diagnosis can be made only by correlating the clinical, radiological and histological findings.


[Serial observations of a pulmonary echinococcus, with rupture into the bronchial system (author's transl)].

The radiological course of an echinococcus cyst of the lung before and after rupture is described, together with the cytological and histological findings. The resultant tissue changes and appropriate treatment (lobectomy) are discussed. In the presence of the appropriate radiological changes, eosinophil granulocytes in the sputum suggest cyst rupture, even in the absence of echinococcus tissue. However, bronchial asthma or Löffler's infiltrates should be excluded clinically. They delayed appearance of peripheral blood eosinophilia after cyst rupture and the development of an eosinophilic broncho-pneumonia is noteworthy.


[Mediastinal and pulmonary complications of the sclerosing treatment of oesophageal varices (author's transl)].

One hundred and twenty patients with oesophageal varices were seen in the surgical clinic between 1970 and 1975; 290 individual treatments with endoscopic sclerosis were carried out. The typical radiological complications in the mediastinum and lungs have been assembled. Clinically significant complications such as oesophageal perforations with large pleural effusions are separated from uni-important complications, such as minor effusions and plate atelectases. The method of conservative treatment of varices is described and the indications for it, as against other forms of treatment, are described.


[A clinical-radiological investigation concerning the accuracy of diatrizoate (Gastrografin) in the demonstration of anastomosis dehiscence and perforation of the gastro-intestinal tract (author's transl)].

A Gastrografin test is described for diagnosing perforations and dehiscence of anastomoses in the gastro-intestinal tract by carrying out a simple urine analysis. False positive and false negative results can be avoided by obtaining radiographs of urine samples under standard conditions. The accuracy of the method was checked in 97 patients by comparing the results of the urine analysis with radiographic examinations and with the clinical course. From this, it appears that the test is reliable, simple and capable of being used anywhere. The test is therefore recommended a) where there is a lack of radiographic facilities, b) for immobile patients, c) where there is clinical suspicion of a perforation or dehiscence of an anastomosis in the absence of radiographic findings and d) in individual cases where the radiographic changes are positive.


[Laevocardiographic evaluation of left ventricular function. III. Aortic valve insufficiency (author's transl)].

1. The normally functioning left ventricle is characterised by a definite relationship between end-diastolic volume and ejection fraction (reduction of lateral systolic projectional area by 50 to 60%. 2. With increasing volume, the left fentricle shows increasing, end-diastolic size. 3. With pure aortic insufficiency, end-diastolic ventricular size is larger than it is with combined aortic valve disease. Hypertrophy is the predominant reaction of the left ventricle to increased resistance, but also to co-existent insufficiency. In addition the ejection fraction rises with increasing resistance. 4. End-diastolic areas up to 85 cm.2 and end-diastolic pressures up to 20 mmHg. can be regarded, rare cases excepted, as indices of normal contraction and are associated with a normal ejection fraction.


[Coronary flow measurements, using cine densitometry. Results using a multiple detector method. I. Normal flow values in healthy and stenosed coronary arteries during rest (author's transl)].

Coronary blood flow was measured by a cine densitometric method using a newly developed system incorporating computer data analysis. The first results concerning front and wave velocity of a selectively injected contrast bolus are reported. Average absolute flow volumes in the right coronary artery are 114 ml. per minute, in the left coronary artery, 88 ml per minute (RIVA = 52 ml/min., RC = ml/min.). There is good agreement with the results of dye dilution and isotope wash out techniques, but the latter are more complicated and less easily reproduced and therefore less suitable for routine use. The results are critically evaluated.


[Varying standard concentrations as a cause of divergent serum digoxin estimations using radioimmune-essays (author's transl)].

1. The results of various commercial radio-immune essays for digoxin differ and cannot readily be compared. 2. For each RIA it is therefore necessary to determine one's own therapeutic and toxic levels in relation to the clinical requirements. 3. When quoting data, it is necessary to define the method of RIA with its therapeutic and toxic levels. 4. A cause for the high digoxin estimations of 2 RIA's carried out by the same firm has been identified as being due to the low concentration of the standard preparation. 5. The introduction of a defined and obligatory digoxin standard is recommended.


[The pharmaco-kinetics of angiographic contrast media with special reference to the extravascular space. Experimental studies on dogs. III. Is there an entero-hepatic circulation of angiographic contrast media? A discussion summarising the results of the entire studies (author's transl)].

The presence of an entero hepatic circulation of angiographic contrast media has been demonstrated, but quantitatively it is of little importance. About 1/2% of the contrast reaching the gut in the bile is reabsorbed and after being carried through the portal vein to the liver is re-excreted in the bile. Most of the contrastcontaining bile reaching the small bowel is excreted in the faeces; nearly all of the contrast absorbed from the colon is carried through the portal vein to the liver and after reaching the circulation is excreted by the kidneys.


[Vitamin D deficiency. Osteopathy after prolonged treatment with anticonvulsents (author's transl)].

Several substances with anticonvulsent activity can lead to hypovitamenosis D after prolonged use through their effect on vitamen D metabolism in the liver. This results in abnormal bone mineralisation and produces rickets or osteomalacia. Radiological examination of the skeleton should be performed on patients receiving prolonged anticonvulsent therapy, in order to arrive at an early diagnosis. This requires an accurate knowledge of the types of bone abnormality and of their most frequent localisation. Pathological findings such as Looser's zones, epiphyseolysis or delayed development must be considered in this context. Radiological examination provides an accurate diagnosis if combined with clinical findings and important biochemical results: reduced calcium and raised alkaline phosphatase. Treatment with vitamen D must then be instituted. Healing may be complete or leave residual changes, depending on the severity of the bone changes.


[Intestinal adaptation of electrolyte and water resorption].

The mammalian intestine is capable of adjusting electrolyte and water transport to the diet by modifying not only total mucosal cell mass but also the functional properties of the absorbing cell. This was demonstrated in the rat cecum where oral application of the polymer polyethylene glycol induced epithelial cell hyperplasia and - functionally - a stimulation of active sodium transport per cell, a higher transmural electrical potential difference and an increased specific activity of the Na-K-ATPase.


Time-course of changes in blood glucose and ketone bodies, plasma lipids and liver fatty acid composition in streptozotocin-diabetic male rats.

Male rats were given streptozotocin (100 mg/kg) by intraperitoneal injection. Groups of control and streptozotocin-treated animals were sacrificed at daily intervals for 4 days after injection. Over this period, treated rats lost weight continuously while control animals progressively gained weight. Within 24 h of treatment blood glucose and plasma free fatty acids were raised to levels which were sustained for the remainder of the experiment. After 48 h blood ketone bodies, plasma cholesterol and triglycerides were maximally raised and liver glycogen and blood lactate similarly lowered. The percentage composition of major fatty acids in liver lipids was unchanged until 4 days after treatment when there were significant increases in the proportion of oleate and linoleate and reductions in stearate and arachidonate. The data confirm that streptozotocin induces a rapid and sustained diabetes. It is suggested that metabolic experiments, in streptozotocin-diabetic rats, may be performed 48 h after treatment.


Testicular lesions of streptozotocin diabetic rats.

Diabetes was induced in adult male albino rats by a single intravenous injection of streptozotocin (75 mg/kg body weight). The diabetes was allowed to stabilize for at least 15 days, whereafter the testicular and seminal vesicle histology was studied at various time intervals. Reduction in testis weights and tubule diameters was significant after 2 weeks of diabetes. The changes in seminiferous tubules ranged from premature sloughing of epithelium to total cessation of spermatogenesis. The testicular histology of diabetic animals frequently greatly simulated the situation described following hypophysectomy. By subjective visual assessment the number of Leydig cells was found to be normal or reduced in all of the diabetic animals. Diabetes was also demonstrated to induce seminal vesicle atrophy, which did not show any correlation with the degree of testicular lesions. The possible etiology of testicular damage in diabetic animals is discussed.


Impaired 3H-testosterone uptake and metabolism in the accessory sex glands of diabetic castrated male rats.

The uptake and retention of 1,2-3H-testosterone in accessory sex glands, muscle and liver of streptozotocin diabetic castrated male rats, insulin-treated diabetic castrated rats and non-diabetic castrated control rats were studied at various time intervals after an intravenous injection. Diabetes reduced the retention of 3H-testosterone in the prostate, the preputial gland and the epididymis. Exogenous insulin slightly increased the retention of 3H-testosterone in these tissues of diabetic rats. No significant differences in the radioactivity in the rectus abdominis muscle, the coagulating glands and the seminal vesicles were found between the various experimental groups. Ventral prostate homogenates obtained from diabetic and control rats were incubated with 3H-testosterone in vitro. The steroids were extracted and thin-layer chromatographs were scanned for radioactivity. In prostatic homogenates taken from diabetic rats, testosterone transformation to dihydrotestosterone was reduced. The results indicate that the impaired function and androgen retention of the accessory sex glands of diabetic male rats is at least partly due to the reduced formation of dihydrotestosterone from testosterone.


Patient work under Fair Labor Standards: the issue in perspective.

The 1973 federal court ruling in Souder v. Brennan required that patient workers in institutions for the mentally ill and mentally retarded be paid in accordance with the minimum wage and other provisions of the Fair Labor Standards Act. The author believes that ruling, which ran contrary to widely accepted institutional practices, is more readily understandable when viewed in the broader context of wage-and-hour legislation. He presents a brief history of the legislation, discusses the provisions relating to the employment of handicapped workers included in the 1966 amendments, and emphasizes that one basic principle underlies all the regulations and procedures: a patient must be paid what he earns. He also urges increased attention to the clinical design of compensated work systems to promote therapeutic and rehabilitative objectives.


Human thymus cells. Excellent responders but poor stimulators in 'One Way' mixed lymphocyte reaction.

Human allogeneic 'one-way' mixed lymphocyte reactions between thymus cells and thymus cells were entirely absent. Of twenty-one mixed lymphocyte reactions between peripheral blood lymphocytes as responding cells and thymus cells as stimulating cells, only eleven had a weak but significant reaction. In contrast, a highly significant response was observed in each of eighteen mixed lymphocyte reactions between thymus cells as responding cells and peripheral blood lymphocytes as stimulating cells and in each of eleven mixed lymphocyte reactions between peripheral blood lymphocytes and peripheral blood lymphocytes. These findings indicate that the thymus cells (T lymphocytes) possess excellent proliferative capacity, with little or no stimulating capacity, while peripheral blood lymphocytes (T and B lymphocytes), on the other hand, are good responders, as well as good stimulators, in the mixed lymphocyte reaction.


Antibody to Physarum myosin. I. Preparation and functional effects.

Preparation of antibody to Physarum myosin is described, and evidence is presented that the antibody is specific for this molecule. A diffusion coefficient of 1 X 10(-7) cm2/s is estimated. The antibody interfered with myosin enzyme activity and with superprecipitation of actomyosin. It did not cross-react with rabbit striated muscle myosin.


[Evaluation of exanthemas following high-dosage intravenous penicillin combinations in intensive care].

118 patients of a non specialized intensive care unit have been studied, all of them under high dose bactericidal cover (10 MIU of Na-Penicillin G and 2,0 Ciclacillin q 12 hrs.) for a period of days to 4 weeks. In 17 (14,4%) a skin rash was observed. 10 of these could be studied using special techniques (radial immunodiffusion, passive hemagglutination, RIST and RAST), however in none of these cases there was a hint of the existence of penicillin specific antibodies. In 6 patients also skin tests were performed. There was no immediate type reaction, only twice delayed type reactions occured to Na Pencillin G.6 patients had continuing treatment on spite of the rash and without further steps the effluorescences vanished within 3-6 days. Therefore continuation of the antibiotic therapy in spite of rash along with strict clinical and laboratory monitoring seems to be preferable to a hastened change of antibiotic regime


Detection of the disabled in a rural area.

A rural Jewish and Arab population of about 24,000 was selected for a rehabilitation study on the disabled. The detection consisted of the collection of existing data from local sources and a door-to-door screening based on an interview schedule. About 22,000 (93%) individuals responded to the interview. In subjects under the age of 65, the degree of agreement between the findings of the door-to-door screening and the information obtained from official local sources was 45.4% among disabled Jewish villagers, and 24% for disabled Arab villagers. On the other hand, in the same age group, the door-to-door interview failed to reveal between 12 to 18% of the subjects reported as disabled by the various local authorities. The reason for this low percentage of agreement is discussed. The disablement rate in the 0- to 13-year age group was 9% for Arab and 12.5% for Jewish children. In the working age group (14 to 64 years) the disablement rate was 5.3% for Arabs and 7.9% for Jews. More than 30% of both Arabs and Jews in this age group had impairments and chronic conditions that did not interfere with their functioning in normal life. In the pensionable age group (65+ years), 8.3% of Arab villagers and 2.3% of Jewish villagers were totally dependent. Special efforts were made to detect the functional limitations of housewives and of the homebound. The interview schedule had a marked educational effect on the professionals and on the villagers. This facilitated the establishment of a rural rehabilitation service in an Arab village, the first service of its kind in Israel.


[Lymphocyte transformation test in Gell's and Coombs' drug reactions].

A method of interpretation of the lymphocyte transformation test is described which results on the basis of statistical evaluation. With this method good results were received in cases of drug induced side effects of type I according to Gell and Coombs. The investigations on 61 patients have shown that differneces between the clinical findings and lymphocyte transformation tests are rare. They are mainly in relation to false-positive reactions of the lymphocyte transformation test in Penicillin allergy.


Recombination in the AM gene of Neurospora crassa--a new model for conversion polarity and an explanation for a marker effect.

It is argued that polarised intragenic recombination is not necessarily due to hybrid DNA extending into the gene for variable distances from one side; it can as well be explained by hybrid DNA usually covering the whole gene, the two complementary DNA strands of the gene having unequal chances of undergoing the interchromatid transfer involved in hybrid DNA formation, and excision from base-pair mismatches proceeding predominantly in one chemical direction (perhaps 5' to 3'). This alternative model for polarity is thought to be in better accord with the behaviour of flanking markers in the am data, which appears to show that conversion-associated crossing-over can occur with almost equal likelihood on either side of the gene (a feature previously held to support negative interference--Fincham, 1974). It also provides an explanation for an unusual marker effect involving two am mutational sites separated by only three base pairs. The nature of the sites (defined by amino acid replacement analysis) is such that one forms a purine-purine mismatch on the same chromatid as the other forms a pyrimidine-pyrimidine mismatch, and vice versa. They show an approximately two-fold difference in recombination frequencies in crosses to other am mutants mapping to the left, and a difference of similar magnitude, but opposite sign, in crosses to mutants mapping to the right.


Hematologic and radiographic changes in cats after inoculation with infective larvae of Dirofilaria immitis.

Hematologic and radiographic findings in 15 domestic cats inoculated with 25, 100, or 200 to 400 infective larvae of Dirofilaria immitis and in 5 uninoculated cats were compared. Eosinophilia and leukocytosis developed 3 to 5 months after inoculation; packed cell volume and hemoglobin values were similar for inoculated cats and controls. Changes detected in radiographs of inoculated cats were: (1) increased visualization of the pulmonary arteries; (2) right-side cardiac enlargement; and (3) diffuse to focal areas of density in the pulmonary parenchyma. At least one of these lesions was visible radiographically by 3 to 7 months after inoculation in all 15 cats. The severity of changes was not directly proportional to the number of infective larvae inoculated, adult worm burden, or age of cat. However, male cats had more severe cardiopulmonary lesions than did females, and cats that had microfilaremia during the course of infection had more severe pulmonary lesions, as determined radiographically. Parenchymal densities decreased in 8 of the 15 inoculated cats 6 to 14 months after inoculation. Cardiac enlargement was detected radiographically in 10 of the inoculated cats. Enlargement of the pulmonary arteries was the most consistent sign of D immitis infection; it developed and persisted in 12 cats found to be infected at necropsy.


Regulation of thymidine metabolism in Neurospora crassa.

The utilization of thymidine by Neurospora crassa is initiated by the pyrimidine deoxyribonucleoside 2'-hydroxylase reaction and the consequent formation of thymine and ribose. Thymine must then be oxidatively demethylated by the thymine 7-hydroxylase and uracil-5-carboxylic acid decarboxylase reactions. This article shows that the 2'-hydroxylase reaction can be regulated differently than the oxidative demethylation process and suggests that the 2'-hydroxylase has, in addition to the role of salvaging the pyrimidine ring, the role of providing ribose not only for the utilization of the demethylated pyrimidine but also for other metabolic processes. One way that this difference in regulation was observed was with the uc-1 mutation developed by Williams and Mitchell. The present communication shows that this mutation increases the activities of the 7-hydroxylase and the decarboxylase but has no comparable effect on the 2'-hydroxylase. Qualitatively similar effects on these enzymes were bought about by growth of wild-type Neurospora in media lacking ammonium ion, such as the Westergaard-Mitchell medium. The 2'-hydroxylase and 7-hydroxylase are also differently affected by the carbon dioxide content of the atmosphere above the growing culture and the growth temperature. Studies with inhibitors indicated that the carbon dioxide effect is dependent on protein synthesis.


Neurospora crassa cytoplasmic ribosomes: cold-sensitive mutant defective in ribosomal ribonucleic acid synthesis.

Experiments were conducted to characterize further the biochemical defects of crib-1 (PJ30201), a coldsensitive mutant strain of Neurospora crassa with a defect in ribosome biosynthesis. The results are as follows. (i) The critical temperature for the expression of the mutant growth and ribosome phenotypes is in the range of 18 to 20 C. (ii) No preferential breakdown of 37S cytoplasmic ribosomal subunits synthesized by crib-1 at 25 C occurs after a shift to 10 C. (iii) Ribosomal subunits synthesized by crib-1 at 25 C function normally in in vivo protein synthesis at 10 C. (iv) Whereas wild type synthesizes both ribosomal subunits in a coordinate manner after either a temperature shift-down (25 to 10 C) of a shift-up (10 to 25 C), noncoordinate synthesis of ribosomal subunits owing to underproduction of 37S subunits occurs in the crib-1 strain immediately after a temperature shift-down. (v) After a shift from 10 to 25 C crib-1 exhibits a 12-h lag before the growth rate and the rate of synthesis of 37S subunits begin to increase significantly. (vi) At 10 C crib-1 synthesizes unequal amounts of 25S and 17S ribosomal ribonucleic acid (rRNA) molecules, resulting from a greatly reduced accumulation of stable 17S rRNA. The mutant phenotypes of crib-1 are proposed to be the result of a defect in rRNA processing.


Expression of the argA gene carried by a defective lambda bacteriophage of Escherichia coli.

Evidence is presented that the increase in specific activity of N-acetylglutamate synthase observed upon heat induction of Escherichia coli (lambdadargA) is primarily due to a gene dosage effect.


Compatibility properties of R483, a member of the I plasmid complex.

R483, an I pilus-determining plasmid previously reported as belonging to a distinct incompatibility group Ibeta, proved to be an atypical Ialpha plasmid; in a growing culture, the degree of inhibition of replication of one Ialpha plasmid by the presence of another was not uniform within the Ialpha group.


Hfr formation by I pilus-determining plasmids in Escherichia coli K-12.

R483, an atypical, I pilus-determining plasmid, and also R144, a typical one, were shown to suppress the DnaA phenotype by integration into the Escherichia coli chromosome.


The stimulus-secretion coupling of glucose-induced insulin release. Fasting-induced adaptation of key glycolytic enzymes in isolated islets.

The rate of glucose and fructose 6-phosphate phosphorylation in islet homogenates is reduced by prior fasting of the donor rats. In fed rats, the velocity of glucose phosphorylation at increasing glucose concentrations (0.1 to 100 mM) is compatible with the presence of two enzyme activities. A preferential effect of fasting upon the high Km enzyme activity can be documented either at low ATP concentration which enhances the fractional contribution of the high Km enzyme activity, or in the presence of glucose 6-phosphate, which suppresses the low Km enzyme activity. Islet phosphofructokinase activity was characterized by inhibition by citrate or high ATP concentrations, and relief from ATP inhibition by AMP. Fasting reduces the activity of phosphofructokinase without altering its sensitivity to ATP and AMP. Cyclic AMP fails to overcome the effect of fasting upon phosphofructokinase. The activity of phosphoglucoisomerase is unaffected by fasting. The fasting-induced adaptation of key glycolytic enzymes could account, in part at least, for reduced metabolism of glucose in islets from fasted rats.


Regulation of cellular growth by sodium pump activity.

Cellular growth has been found to be directly related to the amount of sodium pumping activity in mouse lymphoblasts (L5178-Y) cultured in varying concentrations of the cardiac glycoside, ouabain. No short-term adaptation (within one generation) occured; i.e., neither growth rate nor (Na+ + K+)-ATPase activity increased in cells cultured for  1-2 days in ouabain. Growth inhibition commenced after two hours, occurring concomitantly with decreased 3H-leucine incorporation into protein. The time course of this inhibition of protein synthesis, measured by leucine incorporation was similar to, but slightly slower than the time course or the dissipation of the sodium gradient. On the other hand, 3H-thymidine incorporation is unaffected by ouabain treatment over the same period. The uptake of 3H-alanine, a neutral amino acid thought to be transported via a Na+-dependent carri-r, was depressed concurrently with the sodium gradient dissipation. It is suggested, therefore, that ouabain inhibition of cellular growth results primarily from the dissipation of the sodium gradient leading to decreased Na+-dependent transport of amino acids (e.g., alanine) and, therefore, decreased protein synthesis, as observed by leucine incorporation. A sensitive and rapid method for determining ouabain inhibition of cell volume regulation is also described, which may prove potentially useful for assaying Na pump activity.


[High-pressure liquid chromatography of free and conjugated 17-ketosteroids (author's transl)].

High-pressure liquid chromatography (HPLC) should be used more frequently in biomedical research because heavy molecules can be analysed at ambient temperature without derivatisation to volatile compounds. In this paper the separation of four free 17-ketosteroids, their ester sulfates and glucuronides by reversed-phase HPLC on a Micropak CH column is described. In order to improve the separation several parameters have been studied. Retention data allow comparison of the hydrophilic behaviour of free and conjugated steroids.


Plasma adrenal and gonadal sex steroids in human pubertal development.

Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.


Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding.

The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity. Ability of the myocardial cell to bind tritiated ouabain in vivo was assessed after 1, 2, and 6 h of coronary occlusion followed by 45 min of reperfusion, and correlated with measurements of in vitro (Na+ + K+)-ATPase activity and in vitro [3H]ouabain binding after similar periods of ischemia. Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related. Anterior wall infarction was produced in 34 dogs by snaring of confluent branches of the left coronary system. Epicardial electrograms delineated ischemic and border zone areas. Coronary reperfusion after 2 and 6 h of occlusion was associated with impaired reflow of blood and markedly impaired uptake of [3H]ouabain in ischemic myocardium. In both groups, in vivo [3H]ouabain binding by ischemic tissue was reduced out of proportion to the reduction in flow. Despite near-complete restoration of flow in seven dogs occluded for 1 h and reperfused, [3H]ouabain remained significantly reduced to 58 +/- 9% of nonischemic uptake in subendocardial layers of the central zone of ischemia. Thus, when coronary flow was restored to areas of myocardium rendered acutely ischemia for 1 or more hours, ischemic zones demonstrated progressively diminished ability to bind ouabain. To determine whether ischemia-induced alteration in myocardial (Na+ + K+)-ATPase might underlie these changes, (Na+ + K+)-ATPase activity and [3H]ouabain binding were measured in microsomal fractions from ischemic myocardium after 1, 2, and 6 h of coronary occlusion. In animals occluded for 6 h, (Na+ + K+)-ATPase activity was significantly reduced by 40% in epicardial and by 35% in endocardial layers compared with nonischemic myocardium. Comparable reductions in in vitro [3H]ouabain binding were also demonstrated. Reperfusion for 45 min after occlusion for 6 h resulted in no significant restoration of enzyme activity when compared to the nonreperfused animals. In six animals occluded for 2 h, a time at which myocardial creatine phosphokinase activity remains unchanged, (Na+ + K+)-ATPase activity was reduced by 25% compared with nonischemic enzyme activity. In five dogs occluded for 1 h, (Na+ + K+)-ATPase activity in ischemic myocardium was unchanged from control levels. We conclude that reduced regional myocardial blood flow, local alterations in cellular milieu, and altered glycoside-binding properties of (Na+ + K+)-ATPase all participate in the reduction of cardiac glycoside binding observed after reperfusion of ischemic myocardium. In addition, after 2 or more hours of severe ischemia, myocardial (Na+ + K+)-ATPase catalytic activity is significantly reduced despite incubation in the presence of optimal substrate concentrations.


Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection.

These investigations delineate the recently described suppression of a form of cellular hypersensitivity in mice with streptozotocin-induced diabetes mellitus using a variety of cell-mediated immunologic responses in animals with several different forms of diabetes. Streptozotocin- and alloxan-induced diabetic mice and db/db genetically determined diabetic mice showed reductions in the areas of inflammation around Schistosoma mansoni eggs injected into the pulmonary vasculature of 68, 70, 77%, respectively. In contrast, streptozotocin-induced diabetes had no effect on the nonimmunologic foreign body granuloma around divinyl benzene copolymer beads injected into the pulmonary arterioles. Animals protected from diabetes by treatment with nicotinamide before streptozotocin administration did not develop hyperglycemia and had normal areas of immunologic granuloma formation around schistosome eggs. Treatment with insulin reversed the suppression of schistosome egg granuloma formation in both streptozotocin- and alloxan-diabetic animals. Two additional in vivo parameters of cellular immunologic reactivity were examined in streptozotocin-induced diabetes: delayed footpad swelling was essentially eliminated; skin graft survival across the H-2 area was significantly prolonged from 10.2 days in the controls to 14.4 days in moderately diabetic A/J mice. These observations suggest that diabetes mellitus is associated with suppression of cell-mediated reactions in vivo and that the defect is reversible with insulin treatment.


Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle.

The effect of thyroid status on QO2, QO2 (t) and NaK-ATPase activity was examined in rat skeletal muscle. QO2(t) (i.e. Na+-transport-dependent respiration) was estimated with ouabain or Na+-free media supplemented with K+. In contrast to the effects of ouabain on ion composition, intracellular K+ was maintained at about 125 meq/liter, and intracellular Na+ was almost nil in the Na+-free media. The estimates of QO2(t) were independent of the considerable differences in tissue ion concentrations. The increase in QO2(t) account for 47% of the increase in QO2 in the transition from the hypothyroid to the euthyroid state and 84% of the increase in the transition from the euthyroid to the hyperthyroid state. Surgical thyroidectomy lowered NaK-ATPase activity of the microsomal fraction (expressed per milligram protein) 32%; injections of triodothyronine (T3) increased this activity 75% in initially hypothyroid rats and 26% in initially euthyroid rats. Thyroidectomy was attended by significant falls in serum Ca and Pi concentrations. Administration of T3 resulted in further declines in serum Ca and marked increases in serum Ps concentrations. Similar effects were seen in 131I-treated rats, but the magnitude of the declines in serum Ca were less. The effects of T3 on QO2, QO2(t), and NaK-ATPase activity of skeletal muscle were indistinguishable in the 131I-ablated and surgically thyroidectomized rats. In thyroidectomized or euthyroid rats given repeated doses of T3, QO2(t) and NaA-ATPase activity increased proportionately. In thyroidectomized rats injected with single doses of T3, either 10, 50, or 250 mug/100 g body wt, QO2(t) increased linearly with NaK-ATPase activity. The kinetics of the NaK-ATPase activity was assessed with an ATP-generating system. T3 elicited a significant increase in Vmax with no change in Km for ATP.


Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.


Cutaneous immunohistochemistry. The direct immunoperioxidase and immunoglobulin-enzyme bridge methods compared with the immunofluorescence method in dermatology.

Two immunohistochemical methods, using the enzyme horseradish peroxidase, the direct immunoperoxidase (DIP) and the immunoglobulin-enzyme bridge (IEB) method were applied on 129 skin specimens of 81 patients with lupus erythematosus, bullous pemphigoid, pemphigus vulgaris and rosacea. These methods were compared with each other and with the immunofluorescence (IF) method. The DIP method was preferred to the IEB method because of the greater contrast between the specific staining and the nonspecific staining of the former. The results obtained with both peroxidase methods were comparable with those of the IF method.


The psoriasiform eruption induced by practolol.

Three patients who developed a psoriasiform skin eruption following oral practolol administration are described with particular attention to the cutaneous histological changes. Although the clinical picture resembled psoriasis, the histological one did not, resembling rather that seen in a drug eruption. The possibility of an early lymphoma could not be excluded on purely histological grounds.


The role of plasmin on the double antibody radioimmunoassay of carcinoembryonic antigen in human blood samples.

Double antibody radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) on a series of freshly drawn out concurrent plasma and serum samples of normal human blood donors showed that the serum CEA values were invariably higher than the corresponding plasma CEA values. Extraneous addition of fibrinogen brought down the serum-CEA level to a value comparable to or less than the corresponding plasma value. The effect of certain factors associated with blood clotting, particularly Ca++, fibrinogen, and the fibrinolytic enzyme plasmin, was investigated. Ca++ was shown to play no role whereas the effect of fibrinogen was shown to be indirect in that it served as a specific substrate for plasmin, thereby preventing the plasmin degradation of the primary antibody used in the RIA. The finding stresses the role of enzymes like plasmin in double antibody RIA in general and may explain some of the anomalous results obtained when testing biologic material containing plasmin-like substances.


Increased cytolytic T lymphocyte activity induced by 2-mercaptoethanol in mixed leukocyte cultures: kinetics and possible mechanisms of action.

The 20- to 50-fold increase in cytolytic T lymphocyte (CTL) activity caused by the addition of 50 muM 2-mercaptoethanol (2-ME) at the onset of a one-way murine mixed leukocyte culture (MLC) between C57BL/6 and DBA/2 splenic lymphocytes appears to be unrelated to early events in the culture: if 2-ME was present for the first 24 hr of culture only, there was no increase on day 4, but if addition of 2-ME was delayed until the last 24 hr of culture, the CTL activity was almost as high as that of cultures that were exposed to 2-ME for the entire 4-day culture period. The increase of CTL activity caused by delayed addition of 2-ME ("2-ME rescue") was used to investigate the mechanism by which the thiol induces differentiation of CTL from precursor cells. 2-ME rescue was mimicked by two other thiols, dithiothreitol and cysteamine phosphate, but at higher concentrations. Because the latter compound has no free sulhydryl group until it diffuses into cells and is enzymatically dephosphorylated, we conclude that thiols may increase the differentiation of CTL from precursor cells by an intracellular process involving free sulphydryl groups rather than by interaction with membrane sulfhydryls or destruction of inhibitor cells or their products. Cell separation experiments indicated that 2-ME rescue was independent of the presence of B lymphocytes and of adherent cells (macrophages) and was restricted to a subpopulation of T lymphocytes that developed into large lymphoid precursor cells during the first 3 days in culture even without 2-ME. The development of this subpopulation required DNA synthesis between 24 nad 72 hr after the onset of MLC. When 2-ME was added to day-3 MLC, CTL activity increased slightly as early as 4 hr later, but the major increase occurred during the second half of the 24 hr "rescue"period. Because this increase was inhibited by cytosine arabinoside (ARA-C), it seems likely that DNA synthesis is associated with and may be required for the differentiation of large precursor lymphoid cells into CTL after the addition of 2-ME.


Cell-mediated immune response in vitro. I. The development of suppressor cells and cytotoxic lymphocytes in mixed lymphocyte cultures.

During the in vitro development of cytotoxic lymphocytes (CL), suppressor cells also develop. Spleen cells or lymph node cells harvested from mixed lymphocyte cultures (MLC) on day 2 (day-2 MLC) and added to a fresh MLC suppressed the development of CL. This suppressive effect was sensitive to treatment with anti-theta and C. The suppressive effect of day-2 MLC was not due to cytotoxic effects nor to altered kinetics of the development of both suppressor cells and CL. Although CL develop from hydrocortisone-treated spleen cells, day-2 MLC of hydrocortisone-treated spleen cells did not suppress the development of CL. These studies suggest that suppressor cells and CL are derived from different T cell subpopulations.


Cryopreservation of lymphocytes for use in in vitro assays of cellular immunity.

Human lymphocytes can be cryopreserved for the purpose of performing in vitro tests of cellular immunity. A systematic study of the conditions for freezing and recovering cells has shown that there is wide flexibility in cell concentrations of cryoprotective agent and the temperature and rate of dilution however, have definable optima. Cells frozen and thawed under optimal conditions retain their reactivity in MLC and can be used for sequential studies of immune responsiveness. Approximately 70% of viable and functional cells are recovered when the cells are frozen in 7.5--12.5% DMSO and no further cryoprotection is discernable when up to 50% serum is added to the freezing media. The temperature and rate of dilution are critical only in that cells diluted rapidly in THE COLD (10-fold in 2 min at 0 degrees C) are less responsive in MLC than are cells diluted slowly (10-fold in 10 min) in the cold or slowly or rapidly at room temperature.


Phosphorylation of the red blood cell membrane during the active transport of C++.

The phosphorylation of red blood cell membrane fragments (RBCMF) during Ca++ transport was investigated. When red cell membrane fragments are incubated with [gamma-32P]ATP under the experimental condition which minimizes the phosphorylation of Na+-K+-ATPase, RBCMF are labeled in the presence of Mg++ without Ca++. When Ca++ is added, the labeling decreases due to dephosphorylation of RBCMF. The initial reaction of phosphorylation is reversed in the presence of excess ADP. The treatment of RBCMF with n-ethylmaleimide (NEM) does not interfere with the initial phosphorylation reaction, but blocks the dephosphorylation in the presence of Ca++. These data suggest that the enzymatic sequence of the Ca++ transport mechanism may be very similar to that of the Na+ transport mechanism.


Effects of the Jendrassik manoeuvre on muscle spindle activity in man.

Twenty-eight mechanoreceptive units identified as primary or secondary spindle afferents were sampled from muscle nerve fascicles in the median, peroneal, and tibial nerves of healthy adult subjects. The responses of these units to sustained passive muscle stretch, to passive stretching movements, to tendon taps, and electrically-induced muscle twitches were studied while the subject performed repeated Jendrassik manoeuvres involving strong voluntary contractions in distant muscle groups. The manoeuvres had no effect upon the afferent spindle discharges as long as there were no EMG signs of unintentional contractions occurring in the receptor-bearing muscle and no mechanotransducer signs of unintentional positional changes altering the load on that muscle. Unintentional contractions in the receptor-bearing muscle frequently occurred during the manoeuvres, however, and then coactivation of the spindle afferents was observed. Multiunit afferent responses to Achilles tendon taps, led off from tibial nerve fascicles, were in a similar way uninfluenced by the Jendrassik manoeuvres, even when these resulted in marked reinforcement of the calf muscle tendon jerk. The results provide no evidence for fusimotor sensitization of spindles in muscles remaining relaxed during the Jendrassik manoeuvre, and reflex reinforcement occurring without concomitant signs of active tension rise in the muscles tested is presumed to depend upon altered processing of the afferent volleys within the cord.


Central core disease. A correlated genetic, histochemical, ultramicroscopic, and biochemical study.

Two patients suffering from central core disease are presented. The condition is associated with musculoskeletal abnormalities which have been traced back over five generations. In addition to the typical histochemical findings, electronmicroscopic study has revealed the presence of both structured and non-structured cores in adjacent areas. The calcium uptake by the sarcoplasmic reticulum was reduced to one-third of normal. Phosphorylase activity was normal in the one case and reduced to 63% in the other. Actomyosin Mg2+-activated ATPase activity was decreased, as was the Ca2+-dependent ATPase of the sarcoplasmic reticulum.


Proportion of muscles spindles supplied by skeletofusimotor axons (beta-axons) in peroneus brevis muscle of the cat.

Of 32 cat peroneus brevis spindles, 23 (72%) were found to be supplied by a least 1 skeletofusimotor or beta-axon. A motor axon was identified as skeletofusimotor when repetitive stimulation of it elicited both the contraction of extrafusal muscle fibers and as acceleration of the discharge of primary ending, which persisted after selective block of the neuromuscular junctions of extrafusal muscle fibers. The block was obtained by stimulating single axons at 400-500/s for a few seconds. Of 135 axons supplying extrafusal muscle fibers, 24 (18%) were shown to be beta-axons; 22 beta-axons had conduction velocities ranging from 45 to 75 m/s. All but three beta-axons increased the dynamic sensitivity of primary endings. Beta-innervated spindles may also be supplied by dynamic gamma-axons.


Initial burst of primary endings of isolated mammalian muscle spindles.

The initial burst has been studied in primary endings of isolated mammalian muscle spindles subject to controlled ramp-and-hold stretch. Near the onset of ramp stretch the primary ending discharges at a frequency dependent on stretch velocity. The initial burst is reduced or abolished by repetitive stretch. After block of impulse activity by tetrodotoxin, the receptor potential of primary endings shows an initial component, a rapid depolarization which occurs near the onset of ramp stretch at the same time as the initial burst. This initial component depends, in rate of rise and amplitude, on stretch velocity. It is also reduced or abolished by repetitive stretch. Recording of tension development by the isolated spindle in response to ramp-and-hold stretch shows an early rise in tension associated with the initial burst and the initial component of the receptor potential. This tension rise is also dependent on stretch velocity and is reduced or abolished by repetitive stretch. The results provide direct evidence that the initial burst results from mechanical factors, probably from cross bridge formation between thick and thin filaments as has been suggested (3).


Vitamin A deficiency and the metabolism of glycosaminoglycans and ascorbic acid in the rat.

Weanling rats were fed diets with and without the addition of retinyl palmitate at 6,500 units/kg. The supplemented groups were fed either ad libitum or food was restricted daily to that amount consumed by the group of rats receiving the unsupplemented diet. After a 10 week experimental period, signs of vitamin A deficiency were observed (growth plateau, xerophthalmia) and liver values as retinol were only 1% of control values. Relative to the two control groups, vitamin A deficiency resulted in approximately 30% lower liver, 50% lower blood and 40% lower urinary ascorbic acid. Vitamin A deficiency did not appear to result in significant and direct impairment of GAG sulfate metabolism. Although the total amount of GAG in rat skin was increased, the composition of GAG fractions did not appear to be altered by vitamin A deficiency. Studies regarding the incorporation and disappearance of 35S-sulfate in vivo into GAG fractions obtained from skin indicated no serious impairment in GAG turnover with vitamin A deficiency. Twenty-four hour urine samples were also collected for estimation of 35SO4 excreted in GAG and non-GAG fractions. Likewise, little change was observed with respect to radioactivity associated with sulfate fractions excreted in urine. Although many previous studies have directly linked vitamin A with sulfation of GAG, the results reported here suggest that if there is an alteration in GAG sulfate metabolism, it is probably an indirect consequence of vitamin A status.


Intestinal disaccharidases in the rat: effects of pregnancy and diabetes.

Specific and total activities of lactase, sucrase and maltase were determined in the mucosa scraped from the proximal, mid and distal intestinal segments of nonpregnant and pregnant normal control and diabetic rats. In control rats, pregnancy was accompanied by a significant rise in total lactase activity of the entire intestinal mucosa. This was due to increased specific activity of the enzyme in the mid segment of the pregnant rats. In both nonpregnant and pregnant rats, diabetes was associated with marked enhancement of intestinal growth and with elevated specific and total activities of the three mucosal disaccharidases. In the pregnant diabetic rats, specific and total activities of the disaccharidases were about 30% lower than corresponding values in the nonpregnant diabetic rats.


Alterations in vitamin A metabolism during zinc deficiency and food and growth restriction.

The purpose of these experiments was to further elucidate the effect of the trace element, zinc, on vitamin A metabolism. Three experiments were conducted at two different locations using different sources of animals. A total of 95 rats were used; 71 specific pathogen free and 24 germfree. The results indicate that plasma vitamin A is depressed in zinc deficient animals or animals severely restricted in food and growth. Liver stores of vitamin A were adequate in both groups. Thus, the normal mechanism for maintaining plasma vitamin A appears to be altered by either zinc deficiency and/or severe food and growth restriction.


Sézary's syndrome: a cytogenetic, cytophotometric and autoradiographic study.

Cytophotometric, cytogenetic, and autoradiographic studies were performed in cells of three patients suffering from clinically diagnosed Sézary's syndrome with erythroderma and the presence of abnormal lymphoid cells in the peripheral blood, skin, bone marrow and lymph-nodes. Feulgen DNA cytophotometry of cells in the peripheral blood and skin lesions showed marked aneuploidy and tetraploidy. Multiple translocations were identified with a G-banding technique. The chromosomal abnormalities varied widely between the patients, but C and D group chromosomes were more frequently involved than others. All breakpoints of the translocations were localised in the centromeric region. Autoradiography of blood and skin samples revealed many labelled cells in the skin and a lower number in the blood, indicating cell proliferation in the skin. It is concluded that the pathological cells occurring in the Sézary syndrome are abnormal lymphoid cells with a tendency to proliferate in the dermis. The variability observed between and in the patients is in all probability due to a difference in the degree of dedifferentiation.


The fine structure of neoplastic invasion: invasion of liver, skeletal muscle and lymphatic vessels by the Rd/3 tumour.

Neoplastic invasion as seen in the rat Rd/3 neoplasm has been studied electron microscopically in three sites: abdominal wall, footpad and liver. This neoplasm invades by peripheral cell division and active cell migration. Neoplastic cells protrude many fine processes and compress host cells. Neoplastic cells invade lymphatic vessels in a way similar to that in which white blood cells penetrate them - by the protrusion of fine cytoplasmic processes and passage, sometimes in clumps through open cell junctions. There is no ultrastructural evidence of secretory phenomena.


Specific colorimetric determination of niacinamide in dosage forms.

A chemical method for determining the amount of niacinamide in multicomponent preparations was developed. Neither niacin resulting from the degradation of niacinamide nor vitamin A, thiamine hydrochloride, riboflavin, ascorbic acid, ergocalciferol, or calcium pantothenate interferes. The method is based on the reaction of niacinamide with 1-chloro-2,4-dinitrobenzene, followed by the spectrophotometric measurement of the colored solution obtained after treatment with sodium hydroxide. The proposed method is at least as accurate as the methods currently in use. A structure is proposed for the colored product, and its route of formation is outlined.


The effect of L-tryptophan on spinal cord C-fiber reflexes.

C-fiber reflex were recorded from an ipsilateral S1 ventral root in the acute decerebrate spinal (T10) cat after stimulation of the superficial peroneal nerve. L-Tryptophan, infused in a dose of 150 mg/kg, increased the C-fiber reflex to 210% (S.E.M. +/- 30.1%) of control. This effect was antagonized by cyproheptadine, 0.5 mg/kg. L-Tryptophan increased the C-fiber reflex to 176% (S.E.M. +/- 13.0%) of control after p-chlorophenylalanine pretreatment. Pretreatment of the cats with the decarboxylase inhibitor alpha-methyldopa, 100 mg/kg, 30 minutes before infusion, antagonized the facilitatory effects of L-Tryptophan. L-Tryptophan, 150 mg/kg, had no effect on the monosynaptic or short latency polysynaptic reflexes. 5-Hydroxytryptophan, 20 mg/kg, had erratic effects on the C-fiber reflex producing both facilitation and depression which were not statistically significant. The recovery of tryptamine from brain perfusates, after perfusion of the anterior cerebellum and pons, with a modified Gaddum push-pull cannula, decreased across time. L-Tryptophan caused a slight increase in tryptamine release which was not statistically significant, whereas in cats pretreated with p-chlorophenyl alanine, a significant increase in tryptamine release was seen.


Alterations of synapses on axotomized motoneurones.

1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular electrodes 1-77 days after partial transection of the medial gastrocnemius muscle nerve. 2. Three sequential stages of reaction were defined: (i) firstly, conduction velocity of axotomized motoneurones fell, but e.p.s.p. properties and Ia-motoneurone connectivity were normal; (ii) secondly, e.p.s.p.s became characterized by prolonged rise times and half-widths and by diminished amplitudes; (iii) finally, failures of connectivity were also seen, that is, Ia spindle afferent fibres connected with fewer axotomized than normal homonymous motoneurones. 3. The reason for the change of e.p.s.p. properties cannot be stated with certainty: among the factors may be (i) a change of motoneurone membrane properties and morphology; (ii) partial detachment of synaptic boutons before their total disconnexion, and (iii) detachment of Ia afferent branches terminating on the motoneurone soma before those on the dendrites. 4. The previous conclusion that alteration of e.p.s.p. profiles following motoneurone axotomy was due to total disconnexion of those Ia fibres making synapses on the soma and proximal dendrites ("somatic stripping") must be modified to account for the findings that e.p.s.p. changes are seen before connectivity changes.


Significance of radiologic evidence of free air following laparoscopy.

Electrocautery accidents, especially bowel burns, are one of the major causes of morbidity associated with laparoscopic tubal coagulation. Early recognition of such injury is highly desirable. Radiologic evidence of free air, ordinarily suggesting bowel perforation, may not be of diagnostic significance in such patients. Postlaparoscopic radiologic study of 26 patients revealed significant, projected areas of free air among 38.5% of patients 24 hours later. It is suggested that physicians rely on clinical judgement in cases of thermal bowel injury in the immediate postoperative period.


Experience with the use of the Carboflator for establishing pneumoperitoneum.

Safe and adequate pneumoperitoneum is dependent upon intraperitoneal pressure and not upon the number of liters of gas insufflated. Volume of gas delivered depends upon the size of the patient and whether there is any possible leakage. The Carboflator is a useful instrument for establishing controlled insufflation of gas and fail-safe intraperitoneal pressure.


Histological and histochemical comparisons of muscle spindles in three hind limb muscles of the guinea pig.

Guinea pig soleus, medial gastrocnemius and vastus lateralis muscles were compared for spindle density and distribution, number of intrafusal fibers per spindle and histochemical appearance of the axial bundle. A total of 326 spindles was used in the comparisons. Spindle density was over four times greater in the soleus than in either the medial gastrocnemius or vastus lateralis. In the soleus the spindles were distributed at random, but in the other two muscles no spindles were found in those fascicles in which fast-twitch glycolytic extrafusal fibers predominated. The average number of intrafusal fibers per spindle varied by less than 5% between the three kinds of muscles. About 80% of all spindles located had four intrafusal fibers, two of the nuclear bag type and two of the nuclear chain type. The histochemical appearance of the axial bundle was the same in each kind of muscle. Based on intensities of the myofibrillar adenosine triphosphatase reaction product at polar regions nuclear bag fibers were separable into two histochemical groups; nuclear chain fibers were of only one histochemical type.


Effect of PS-K, a protein polysaccharide, on pulmonary metastases of a C3H mouse squamous cell carcinoma.

We studied the effects of PS-K, a protein polysaccaride isolated from a basidiomycete, on the formation of blood-borne metastases. Experimental tumors were fifth-generation isotransplants of a spontaneous C3Hf mouse squamous cell carcinoma that was weakly antigenic. A single-cell suspension from fourth generation tumors was transplanted, and the tumor-bearing legs of the mice were amputated when transplants reached a certain diameter. Daily administrations of PS-K followed immediately, and both lungs were excised on the 21st postamputation day. The number of lung colonies formed on the surfaces of both lungs was counted and total  volumes of metastatic colonies were estimated. PS-K, if administered alone, did not inhibit the lung colony formation. Marked reduction in this formation was observed when five daily doses of PS-K were administered simultaneously with cyclophosphamide. These observations indicate that PS-K may be a potent agent in the therapy of cancer if used as an adjuvant to a chemotherapeutic agent.


Schedule-dependent effect of phase-specific cytotoxic agents on production of hemolytic plaque-forming cells.

The proliferative phase of the primary response of mice to sheep red blood cells (SRBC) was used to study quantitatively the schedule-dependent effect of four phase-specific cytotoxic agents: 1-beta-D-arabinofuranosylcytosine (ARA-C), methotrexate (MTX), 5-fluorodeoxyuridine (5-FUDR), and 5-fluorouracil (5-FU). The multiple injections of ARA-C- GIVEN 24-60 HOURS AFTEr SRBC injection caused a 100-fold greater inhibition in the production of direct hemolytic plaque-forming cells (PFC) on day 4 than the maximum inhibition obtained by a single injection. A similar, but lesser, enhancing effect was observed with 5-FUDR. Although a single injection of either MTX or 5-FU given 24 or 48 hours after the immunization alone was effective in suppressing PFC production, multiple injections of MTX at 6-hour intervals could cause the same degree of inhibition with a smaller total dose. In contrast, there was no difference for 5-FU, whether given as a single injection or in a divided dose. When only two doses of cytotoxic agents were used, 8- and 14-hour intervals with ARA-C and MTX, respectively, gave the maximum degree of inhibition.


In vitro lymphocyte dysfunction in Hodgkin's disease.

In vitro lymphocyte function and delayed cutaneous hypersensitivity (DCH) response in vivo were assessed in 27 patients with Hodgkin's disease. Lymphocyte responsiveness to phytohemagglutinin (PHA) and to a standard mitomycin C-treated lymphoblastoid cell line in a one-way mixed lymphocyte culture (MLC) was measured simultaneously and compared to that of controls. Seventeen patients, including 6 of 11 untreated patients, had some defect either of DCH or of an in vitro lymphocyte function. In patients lacking a DCH response, the PHA and MLC responses were significantly depressed as compared to either those with intact DCH or normal controls. In patients with intact DCH, the PHA but not the MLC response was significantly depressed. PHA stimulation and MLC may define different subpopulations of responding thymus-derived lymphocytes in patients with Hodgkin's disease. Measurement of lymphocyte response to PHA and to a standard lymphoblastoid cell line in the one-way MLC may provide complementary in vitro means of assessing cell-mediated immunity in patients with Hodgkin's disease.


Management of massive abdominal wall defects: role of porcine skin grafts.

Primary closure with "minimal tension" of an inadequately debrided massive abdominal wall defect invariably results in further necrosis and dehiscence. Rotation flaps and prosthetic materials are potentially hazardous in severely traumatized and contaminated wounds. An alternate technique, utilizing an abdominal wall pack and porcine skin graft has been used in two patients with close-range shotgun blasts and one patient with postoperative necrotizing fascitis. The combination of a biological dressing and an abdominal wall pack, stinted by strategically placed retention sutures, controls infection, promotes healthy granulation tissue, and prevents bowel erosion with fistula formation.


Linear abdominal trauma.

Three cases of blunt abdominal trauma are presented to exemplify the mechanism of trauma and the problems of diagnosis associated with any linear blow to the abdomen. The mechanisms of visceral injury are reviewed, and special attention is directed to the abdominal wall injury that can be present in these patients. This injury has special implications in directing the operative approach and repair. An unusual aortic occlusion is described which is peculiar to this type of injury.


Bacteriophage T4 head morphogenesis. VII. Terminal stages of head maturation.

Several aspects of the terminal stages of T4 head maturation were investigated using ts and am mutants blocked at single steps of the assembly pathway. We had previously found that cells infected with mutants of gene 13, e.g., tsN38 and amE609, accumulated both stable (10 to 20%)- and fragile (80%)-filled head precursors (Hamilton and Luftig, 1972). Here we showed the following for such gene 13-defective, mutant-infected cells. (i) Using thin-section analysis the pool of phage precursor structures observed under nonpermissive conditions was one-third of that observed when the cells were cultured under permissive conditions. (ii) In order for complete conversion of the precursors into viable phage to occur, there were apparent requirements of metabolic energy, protein, and DNA synthesis. (iii) The intracellular DNA pool under nonpermissive conditions exhibited a 50% distribution between 63S (mature size) and 200 S (concatenate size) DNA, with the latter DNA serving as a precursor pool. Further, this DNA pool when spread onto a protein monolayer exhibited a dispersed array of DNA, strands around a core, which was less dense than that found for the greater than 1,000S DNA concatenate isolated from gene 49-defective infected cells. (iv) When precuations were taken to stabilize the head precursors, such as lysis of the cells into glutaraldehyde, there was a 30% increase in the yield of 1,200S filled heads. Correlating these results and previous results concerning gene 49-defective unfilled heads, we propose that there are several forms of gene 13 fragile head precursors which serve as intermediates between gene 49 unfilled heads and gene 13 stable filled heads. We cannot, however, rule out the possibility that all gene 13-defective heads represent a single class of unstable particles, which decay slowly. In either case, we have shown that gene 13-defective particles are unstable to some degree inside the cell and are highly unstable outside the cell; yet all particles can still be efficiently converted to phage in vivo.


Postinfection control by bacteriophage T4 of Escherichia coli recBC nuclease activity.

Infection by bacteriophage T4 has previously been shown to cause a rapid inhibition of the host recBC DNase, an ATP-dependent DNase that is required for genetic recombination in Escherichia coli. We report here the partial purification of a protein ("T4 rec inhibitor") from extracts of T4-infected cells and some characteristics of the in vitro inhibition reaction with purified inhibitor and recBC nuclease. This inhibitory activity could not be purified from extracts of uninfected E. coli. Both the ATP-dependent exonuclease and DNA-dependent ATPase activities of recBC DNase are inhibited by T4 rec inhibitor. Experiments suggest that the inhibitor interacts with the nuclease in a stoichiometric manner. The biological significance of this inhibition is discussed with respect to control reactions in phage-infected cells.


Fate of input oncornavirion RNA--biological studies.

The fate of input Friend leukemia virus RNA was studied using labeled input virus. The appearance of nuclear RNA-DNA hybrid molecules and the apparent integration of input virion RNA with host cell DNA was studied using a series of inhibitors of DNA or protein synthesis, cell growth conditions, and an intercalating agent. Under all these conditions of infection, little to no viral-specific RNA-DNA hybrid molecules were formed. These data demonstrate that the formation of such RNA-DNA hybrid structures requires conditions of infection that allow provirus synthesis and integration. Furthermore, they suggest that at least a fraction of input virion RNA may transiently become integrated with host cell DNA.


Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.


Concanavalin A perturbation of membrane enzymes of mammary gland.

The plant lectin concanavalin A (Con A) specifically inactivates the 5'-nucleotidase of a plasma membrane-enriched fraction from lactating mammary gland. The lectin also causes an activation of the membrane Mg++-ATPase, but does not affect galactosyltransferase or alkaline phosphatase. The enzyme perturbations are prevented by alpha-methylmannoside, an inhibitor of Con A binding, indicating that specific binding to carbohydrate structures rather than nonspecific protein-protein interaction is involved. Solubilization of the 5'-nucleotidase in detergents (0.2% Triton X-100 or 1% deoxycholate) does not prevent Con A inactivation, indicating that incorporation into the membrane structure is not a requirement for the Con A effect. the results suggest that Con A inactivates the 5'-nucleotidase by a direct interaction with the enzyme and that this enzyme is a Con A receptor site on the surface of mammary cells.


An aetiological study of 1,000 patients with an I.Q. assessment below 51.

This paper examines the actiological basis of the severer grades of mental retardation in 1,000 individuals attending an outpatient clinic. It was found it was possible to make a suggested diagnosis in 78% of cases. These fell into broad aetiological groups: genetically determined, 25%: early prenatal abomalies, 18%: perinatal damage, 17% prenatal and postnatal infections, 15%; cultural disintegration, 3%. The changing pattern of incidence and the possibilities of prevention are discussed for each group.


Membrane adenosine triphosphatase of Micrococcus lysodeikticus. ISolation of two forms of the enzyme complex and correlation between ezymatic stability, latency and activity.

Two new forms of the plasma membrane ATP-ase of Micrococcus lysodeikticus NCTC 2665 were isolated from a sub-strain of the microorganism by polyacrylamide gel electrophoresis. One of them had a mol.wt of 368,000 and a very low specific activity (0.80 mumol.min-1.mg protein-1) that could not be stimulated by trypsin. This form has been called B1 (strain B, inactive). If the elctrophoresis was carried out in the presence of reducing agents (i.e., dithiothreitol) and the pH of the effluent maintained at a value of 8.5 another form of the enzyme was obtained. This had a mol.wt of 385,000 and a specific activity of 2.5-5.0 mumol.min-1.mg protein-1 that could be stimulated by trypsin to 5-10 mumol.min-1.mg protein-1. This preparation of the ATPase has been called from BA (strain B, enzyme active). The subunit composition of both forms has been studied by sodium dodecyl sulphate and urea gel electrophoresis and compared to that of the enzyme previously purified from the original strain (form A). The three forms of the enzyme had similar beta and delta subunits, with mol.wt of about 50,000 and 30,000 dalton, respectively. They also had in common the component(s) of relative mobility 1.0, whose status as true subunit(s) of the enzyme remains yet to be established. However, subunit alpha, that had a mol.wt of about a 52,500 in form A (ANDREU et al. Eur. J. Biochem. (1973) 37, 505-515), had a mol.wt similar to beta in form B1 and about 60,000 in form BA. Furthermore BA usually showed two types of this subunit (alpha' and alpha") and an additional peptide chain E) with a mol.wt of about 25,000 dalton. This latter subunit seemed to account for the stimulation by trypsin of form BA. Forms BA could be converted to B1 by storage and freezing and thawing. Conventional protease activity could not be detected in any of the purified ATPase forms and addition of protease inhibitors to form BA failed to prevent its conversion to form B1. The low activity form (B1) was more stable than the active forms of the enzyme and also differeed in its circular dichroism. These results show that M. lysodeikticus ATPase can be isolated in several forms. Although these variations may be artifacts caused by the purification procedures, they provide model systems for understanding the structural and functional relationships of the enzyme and for drawing some speculations about its function in vivo.


Balkan nephritis. A synthetic view on 50 studied cases.

Epidemiological, clinical pathological investigations concerning Balkan nephritis (BN) have revealed some particular aspects which define this condition as a distinct nosologic entity. Its endemic familial character and its occurrence restricted to some limited geographic areas in Bulgaria, Yugoslavia and Romania, are highly unusual. BN leads to chronic impairment of the renal function which is, however, not constantly associated with edema and hypertension. The duration of the disease is prolonged; death takes place from uremia within five to ten years. Gross pathologic changes are consisting of severe bilateral atrophy of the kidneys, with structural changes suggesting a 'renal cirrhosis'. The etiology of the disease is obscure. Investigations carried out by means of electron microscopy and immunofluorescence tests are suggesting that the pathogenesis is rather complex. The role of a persistent tolerated or slow, latent virus infection in certain families, that of some toxic factors, and the implication of autoimmune mechanisms are to be considered.


Morphogenesis and pathogenesis of chronic lung diseases. X. An anatomoclinical and pathogenetic study of 48 pseudotumoral chronic pneumonites.

Forty-eight cases of operated pseudotumoral chronic pneumonites were anatomoclinically and histogenetically studied. Two groups of cases can be established. The first one (21 cases), in which the histogenetic mechanism is related to previous bronchopulmonary infections, suppurations, and immune processes of the immediate type, is characterized by numerous granulocytic foci, granulomatous structure, Arthus type vasculites and fibrous evolution. The unefficient therapy could be one of the determining factors of this evolution, by maintenance of active germs and released antigens. The second group (27 cases) is characterized by hypertrophic bronchites reflecting the prolonged penetration of airborne antigens, by a step by step involvement of peribronchial and parenchymatous structures. A multiphasic development is comparatively demonstrated in the different cases, and dominated by various proportions of plasmocytes and fibroblasts interfering with a restorative granulomatous process involving the intra- and interlobular areas and evolving to a fibrogranulomatous state. Obstructive pneumonitic phenomena and reactive endoalveolitis obliterans interfere, too. Correlations between the dynamics of this picture and the experimental data assert an immune mechanism with repeated immediate and delayed hypersensitivity reactions and auto-aggressive phenomena, determined by released antigens and inductors of cell proliferation and differentiation, as the main processes conducing to the building up of the pseudotumoral chronic pneumonites.


The size distribution of thyroid follicles in single thyroid glands, a peculiar problem of particle size distribution in stereology.

Follicle sections vary in size according to their inclination mainly in hypertrophied thyroids. Sagittal sections elicit a shift to small classes, while transversal sections, to large classes. There is no mathematical transformation able to convert data obtained by sections into "true" sizes of follicles, as may be achieved by isolation. All papers emphasizing only section diameters and inferring about follicle size must be cautiously interpreted, and even discarded, if they tend to establish differences in follicle size solely on that basis. Follicle isolation is necessary if we need to establish follicle size and shape. Although proportions are almost stable for rats of the same age and weight, the proportions of follicle size may vary, as dependent on age and other internal and external conditions. The situation is most complicated by colloid accumulation; but despite these impedimenta, TSH secretion enlarges the follicles, a situation hitherto not well established. Cell enlargement is consequently followed by follicle enlargement, despite colloid resorption.


Rhythmic circadian activity of the rat hepatic lobule reflected at cellular level.

Study of the liver by quantitative microscopic methods (karyogram, nucleologram), cytophotometry and karyometry demonstrated the circadian rhythmicity of the different nuclear variables in terms of the functional activity of the cells. In the hepatic lobule of the adult rat, synchronized to a fixed feeding hour, a cellular rhythmic self-renewal was recorded, especially due to ploidization, with cytotopographical particularities, consisting in the cyclic reversible transformation of diploid into polyploid cells (with a single hypertrophic nucleus or binucleate) according to the increased metabolic requirements in the course of digestion.