Nursery outbreak of scalded-skin syndrome. Scarlatiniform rash due to phage group I Staphylococcus aureus.

From Aug 6 to 14, 1973, scariatiniform eruptions that were considered to be mild forms of the staphylococcal scalded-skin syndrome developed in four neonates. One infant had mild epidermal peeling. All had generalized, finely papular erythema that cleared rapidly after treatment with antibiotics. Cultures from the umbilical stumps or anterior nares of three of the infants yielded colonies of group I Staphylococcus aureus, phage type 29/52/79/86/D11/81, that were able to produce epidermal exfoliation in suckling mice. These data indicate that the nursery outbreak was caused by phage group I staphylococci rather than group II organisms previously associated with staphylococcal scalded-skin syndrome. The demonstration that a group I Staphylococcus can produce exfoliative toxin suggests that the same mechanism for toxin production may exist for phage groups I and II staphylococci.


[Study of drug allergies with special reference to skin manifestations].

One hundred and forty four patients, with dermal reactions to different drugs, were chosen from our clinic. The selection criteria was based on a detailed and careful anamnesis in order to be certain of the specific drug responsible for the reaction. We tried to establish a drug-specific reaction pattern for each of the drugs studied. Intradermal skin tests were performed with all drugs to be studied, except with pyrazolones and aspirin, for which patch tests were applied. The drug concentrations were established prior to the tests in order to avoid unwanted unspecific reactions. In every case, immediate and delayed reaction readings were carried out. A three crosses reaction (+++) was considered positive. The skin tests were positive in 44% of the cases, a value higher than those referred to by most authors. The delayed reactions to skin tests and the chloramphenicol-mediated delayed-type "dermatitis-like" manifestations are compared. It is noteworthy to mention that positive delayed reactions were observed more frequently with chloramphenicol than with any of the other studied drugs. The same applies for those patients with a positive history to chloramphenicol. The most common reaction pattern to penicillin and streptomycin in our series (20%) were urticaria and Quincke's edema. Penicillin, pyrazolones and streptomycin were the most common drugs responsible for urticarial patterns, being the pyrazolones related to fixed erythema in many cases. The age group 25-50 was the most frequently involved. No sex predominance was observed. The value of the classic skin tests is discussed, so are history recording and the in vitro tests.


Comparison of culdoscopic and laparoscopic tubal sterilization.

The growing number of women requesting interval sterilization (apart from term delivery or abortion procedures) necessitates the re-evaluation of traditional surgical procedures. A total of 800 women--the first 400 women undergoing culdoscopic and laparoscopic tubal sterilization procedures at Siriraj Hospital in Bangkok, Thailand--evaluate the appropriateness of the two sterilization procedures for use in interval sterilization programs. No serious operative complications occurred in either group. However, the rate of postoperative complications was considerably higher for the culdoscopic group than for the laparoscopic group. Hospitalization was required for only a small percentage of the patients and most had resumed their normal activities within two days of the operation. This study indicates that both procedures are effective and may be safely performed on an outpatient basis without general anesthetics and with minimal discomfort for the patients.


Treponemal antigen in immunopathogenesis of syphilitic glomerulonephritis.

A patient with syphilitic glomerulonephritis had a renal biopsy and was treated for secondary syphilis. Light, electron, and immunofluorescence microscopic studies revealed an acute proliferative glomerulonephritis with subepithelial, intramembranous, and subendothelial immune complex deposits containing IgG, IgA, IgM, C4, and C3. Similar local deposits containing predominantly IgM were noted in areas of mesangial proliferation. Indirect fluorescent antibody studies employing rabbit treponemal antibody and sheep antirabbit globulin conjugate revealed the presence of treponemal antigen in the glomerular deposits. This finding provides strong evidence for the immunopathogenesis of the glomerular lesion as well as a causal link with Treponema pallidum.


Case report. Congestive heart failure complicating the hungry bone syndrome.

A patient with the hungry bone syndrome following parathyroidectomy for hyperparathyroidism developed congestive heart failure, probably due to the myocardial depressant effects of hypocalcemia and hypomagnesmia. Calcium and magnesium alone were instrumental in relieving his symptoms, decreasing his heart size, and clearing the pulmonary congestion. A mechanism for the pathogenesis of hypocalcemia and hypomagnesemia induced heart failure is proposed.


Inguinal hernia repair. A comparison of the Shouldice and Cooper ligament repair of the posterior inguinal wall.

The basic principle of the Cooper ligament repair is the closure of the deficiency in the posterior inguinal wall effected by suturing the upper margin of the defect, represented by the aponeurosis of the transversus plus its investing fascia, downwards to its insertion  on to Copper's ligament along the superior ramus of the pubis lateral to the pubic tubercle. Because of tension, a relaxing incision in the anterior rectus sheath is frequently necessary. The basic principle of the Shouldice repair of the posterior inguinal wall is an overlapping repair utilizing the transversalis fascia, previously divided from internal ring to pubic tubercle. The lateral (or lower) transversalis flap is anchored upwards, underneath the medial (or upper) flap, being attached medially to the edge of the rectus and laterally to the arching fibers of transversus and internal oblique. The medial flap is then attached to the deepest part of the shelving surface of the inguinal ligament. Tension is a less significant factor and a relaxing incision is not used. In two large well-documented series, each using one of these technics exclusively, the recurrence rates are used to compare these two methods of repair. In Halverson and McVay's twenty-two year series of 263 repairs for primary direct inguinal hernia, using the Cooper ligament method throughout, this rate was 4.9 per cent. In my personal twenty-one year series of 4,812 primary direct inguinal hernia repairs using the Shouldice method exclusively, a recurrence rate of 0.7 per cent was achieved. These results suggest that the Shouldice repair is superior.


Laparoscopy in the diagnosis of blunt and penetrating injuries to the abdomen.

Laparoscopy was evaluated in thirty-seven patients from a group of 132 consecutive patients who were treated for blunt or penetrating injury to the abdomen. A total of twenty-three patients underwent laparoscopy and laparotomy. The findings at laparotomy correlated with laparoscopy. Fourteen patients underwent laparoscopy only, and there were no proved false-negative results. Of the 132 patients considered for laparotomy, 118 underwent abdominal exploration. Laparotomy was considered unnecessary in twenty-five of the 118 patients (21 per cent) and in retrospect, laparoscopy could have identified in each patient the presence of a minor injury or no injury at all. Laparoscopy is a useful method for evaluating blunt and penetrating injuries to the abdomen in selected patients.


Laparoscopy in general surgery.

In the last seven years laparoscopy has become increasingly popular in North America. The procedure has been mainly embraced by the gynecologist. Other specialities have been relatively slow in recognizing its value. Laparoscopy has wide applications in general surgery. It is a useful tool in blunt abdominal trauma and often prevents laparotomy. In patients with acute abdominal conditions, when findings are atypical, uncertainty in diagnosis may be resolved by laparoscopy. In patients with malignant disease it permits assessment of the extent of the lesion and enables accurate selection of the mode of therapy. Numerous procedures per laparoscopy, including biopsies, division of adhesions, cholangiography and collection of samples for bacteriologic studies, may be carried out simultaneously. Complication associated with the procedure are few but may be severe. These can be avoided by careful adherence to proper technic.


Extraperitoneal retention sutures.

A new technic for the application of retention sutures is described. Intestinal obstruction caused by the entrapped intestine between the retention suture and the abdominal wall is practically eradicated with this technic.


[Adenoma of the pigmented ciliary epithelium (author's transl)].

A solid adenoma of the pigmented ciliary epithelium was removed by 9.0 X 6.0 mm "block-excision" (postoperative visual acuity 1.0). The black lesion with a velvety surface consists of very large cells packed with melanin granules of abnormal and variable density, structure and size. Striking intracellular vacuoles contain acid mucopolysaccharides, particularly sialomucins. The literature on tumors of the pigmented ciliary epithelium is reviewed. Criteria for the separation of adenomas for adeno- "carcinomas" (8 cases, all without metastases) from reactive hyperplasia (6 cases) are proposed. The histologic, histochemical and electronmicroscopic findings of our tumor show striking similarities to those of an adenoma of the retinal pigment epithelium.


Fiber types and size in equine skeletal muscle.

Frozen sections of equine musculus semitendinosus were examined for myosin adenosine triphosphatase (ATPase) and reduced nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR), using standard histochemical procedures, and the proportions of the various fiber types and average fiber sectional size were determined. With ATPase staining, approximately 70% of the fibers were classified as alpha fibers (ATPase positive), and 30%, as beta fibers (ATPase negative). In addition, 2 populations of alpha fibers could be readily distinguished on the basis of the intensity of the ATPase reaction, and these were designated alpha positive and alpha intermediate. The relationship of this difference in ATPase reaction to contraction speed of the fibers is not known. With NADH-TR staining, fibers were classified as either red fibers (positive) having aerobic metabolism or white fibers (negative) having primarily anaerobic metabolism. All beta fibers were red by NADH-TR; thus, they conformed to the criteria for beta R fibers. All alpha positive fibers were white by NADH-TR, as were most of the alpha intermediate fibers, and would be classified alpha W. Some of the alpha intermediate fibers gave an intermediate reaction with NADH-TR and could be classified as alpha R fibers which have not transformed to alpha W fibers. The alpha positive fibers were 7 to 10 mum larger in diameter than either beta or alpha intermediate fibers.


Cardiovascular changes during laparoscopy. Studies of stroke volume and cardiac output using impedance cardiography.

The stroke volume and cardiac output changes in twenty-four patients undergoing laparoscopy were measured using the non-invasive technique of impedance cardiography. There was a moderate fall of stroke volume and cardiac output during intraperitoneal insufflation of carbon dioxide which was directly related to the volume of gas used. The need for caution during laparoscopy particularly in ill patients is emphasised.


The avoidance of suxamethonium pain: a study of patients presenting for laparos copy.

A comparison was made of the incidence of post-operative pain in patients given suxamethonium modified by pre-treatment with a small dose of gallamine and those not given suxamethonium. Sequential analysis of the results showed a preference for anaesthetic techniques not employing suxamethonium.


Staphylococcus aureus infections of captive dolphins (Tursiops truncatus) and oceanarium personnel.

Samples from blowhole and pharynx of 1 dolphin ill with a respiratory tract infection and 31 healthy dolphins at 2 oceanariums were examined by bacteriologic cultural technique. During the same period, nasal and volar forearm skin samples were collected from 32 healthy personnel and from a furuncle on the forearm of 1 attendant. Coagulase-positive staphylococci were isolated from 8 dolphins (including the ill dolphin) and from 14 persons. Antibiotic sensitivity patterns (8 drugs were tested) differed markedly for the staphylococcal isolates recovered from dolphins, as compared with those from persons. Staphylocci from the dolphins were totally or partially sensitive to every antibiotic, whereas almost all of the isolates from persons were resistant to penicillin and ampicillin, as well as to certain other antibiotics. Staphylococcus bacteriophage typing revealed that only 1 isolate from a dolphin could be typed (type D11). Six of the isolates from persons were typable, but no isolate was sensitive to only type D11. It was concluded that, although Staphylococcus aureus could be isolated commonly from captive dolphins, there was no evidence of cross infection between the dolphins and the oceanarium personnel.


"Pentazepam" (pentazocine + diazepam) supplementing local analgesia for laparoscopic sterilization.

Salpingectomy by laparoscopy in 200 healthy outpatients employed local analgesia and "pentazepam" (pentazocine 90 mg and diazepam 30 mg in 250 ml of 5% D/W) as anesthesia. Patients received no premedication, ventilated spontaneously, without tracheal intubation, but were given nasal O2 at 3 L/min throughout the procedure. N2O was used for abdominal insufflation, and the abdominal pressure and Trendelenburg position were restricted to less than 20 cm H2O pressure and 30 degrees, respectively. Changes in arterial blood gases measured in 12 patients were unremarkable. Prolonged recovery, unsatisfactory surgical conditions, tachycardia, nausea and vomiting were infrequent.


Nephrotic syndrome associated with Fanconi Syndrome. Immunopathogenic studies of tubulointerstitial nephritis with autologous immune-complex glomerulonephritis.

The nature of renal lesions in a patient with simultaneous onset of the Fanconi syndrome and nephrotic syndrome was investigated by immunologic studies of the patient's serum, cryoproteins, and renal tissue. Acute severe tubulointerstitial nephritis and generalized segmental glomerulonephritis were present. Renal tubular epithelial (RTE) antigen, IgG, and Clq were localized in the glomerull and proximal tubules. Cryoprecipitates containing RTE antigen and anti-RTE antigen were isolated from the patient's serum antibody to RTE antigen was detected in the serum of the patient. However, antibody to tubular basement membrane was not found in the cryoproteins or serum. The unusual simultaneous presentation of these two syndromes in our patient possibly represents a common etiology: tubular damage with release of RTE antigen and subsequent development of immune-complex glomerulonephritis mediated by renal tubular epithelial antigen and antibody to this antigen.


Resolution and reconstitution of ion-transport systems.

1. Oxidative phosphorylation was reconstituted with a mitochondrial proton pump (oligomycin-sensitive ATPase) and segments of the oxidation chain (cytochrome oxidase or DPNH-Q1 reductase). A proton pump of bacteriorhodopsin substituted for the respiratory chain components, giving rise to light-induced ATP formation. 2. Since oxidative phosphorylation has thus become a special case of the problem of ion translocation in general, we have investigated and reconsituted other pumps. The reconstituted Ca++ pump of sarcoplasmic reticulum consists of two factors, the Ca++-dependent ATPase and a heat-stable coupling factor. 3. Other information obtained from reconstitution experiments include the role of asymmetry in organized membranes and the specificity of protein-phospholipid interaction. 4. Purified preparations of Ca++-ATPase catalyze the formation of ATP from Pi and ADP in a stepwise reaction stoichiometric with the enzyme and dependent on Ca++.


Cellular thermogenesis.

The principal conclusion presented in this review is that no single mechanism underlies any of the examples of basal or altered cellular thermogenesis. Both increased Na+ pump operation and uncoupling may occur to a greater or lesser extent, as may other heat-producing mechanisms. There are areas in which further information is needed in order to explain fully the composite nature of the mechanisms involved in cellular thermogenesis. The control of mitochondrial oxidations in their natural habitat (i.e. inside cells) by regulatory proteins, fatty acids, ions (Ca2+, Na+, K+), cyclic AMP, protein kinases, prostaglandins, purine nucleotides, and other factors must be elucidated. There is evidence for the participation of all of these substances in the control of cellular thermogenesis, but no scheme has been developed that takes them all into account. Further emphasis on the tissue-specific differences in the regulation of mitochondrial function is desirable. The regulation of the biogenesis of mammalian mitochondria is another area currently under intense study for which no clear hypothesis has as yet emerged. Information in this area is needed in order to understand the mechanism and role of mitochondrial adaptations associated with altered thermogenesis in hyperthyroidism, in acclimation to cold, and in exercise training, as well as the nature of altered mitochondrial biogenesis, such as appears to underlie the Luft hypermetabolic syndrome.


Renal tubular chloride transport and the mode of action of some diuretics.

The renal diluting segment (thick ascending limb of Henle's loop) reabsorbs sodium chloride in excess of water and is responsible for dilution of the urine as well as reabsorption of a large fraction of the salt present in the glomerular ultrafiltrate. There is active reabsorption of chloride, which causes the voltage to be positive in the tubule lumen. Most, if not all, of the sodium transport is passive, driven by the voltage. Three major diuretics (mersalyl, furosemide, and ethacrynic acid) act in the lumen of the diluting segment to inhibit active chloride transport, not sodium transport as previously believed. This specific action on chloride transport may explain how these drugs are able to inhibit salt transport in the kidney while having so little effect on the transport processes elsewhere in the body.


Effects of enterocin E1A on the ultrastructure of Streptococcus faecium.

Streptococcus faecium 158 cells were examined by electron microscopy at sequential intervals after addition of enterocin E1A, a bacteriocin produced by Streptococcus faecium E1. After addition of enterocin E1A, the nuclear material began to concentrate into distinct areas at the center of the bacteria. In a later stage, extensive condensation of the nuclear filaments left a small cluster of dense granules within a cytoplasmic vacuole, and 10-20% of the cells underwent a complete lysis.


Role of microorganisms in dandruff.

The role of microorganisms in dandruff was studied, by suppressing individually and then collectively the three major components of the scalp microflora. The effect on dandruff was assessed subjectively by clinical grading and objectively by the corneocyte count. No effect on dandruff was demonstrated when scalp organisms were suppressed. In the second group of experiments, dandruff was suppressed by selenium sulfide shampooling and the effect of continued suppression of Pityrosporum with topically applied amphotericin was measured. According to our criteria, dandruff returned to pretreatment levels, despite continued suppression of Pityrosporum. The studies demonstrate that the increased number of scalp microorganisms found in dandruff occurs as a secondary event to increased nutrients and that scalp organisms play no primary role in the pathogenesis of dandruff.


Potential hazards of clindamycin in acne therapy.

In the course of the last two years, a tremendous amount of controversy has been raised over dangers accompanying the use of the antibiotic clindamycin. The controversy has been stimulated by recent reports of fatalities from pseudomembraneous colitis associated with clindamycin therapy. Varying greatly in degree of severity, the colitis has been reported in as high as 10% of all patients using the drug. The pertinence of such data, however, in a young, healthy acne population receiving small maintenance doses is questionable. Nevertheless, because of these reports, the use of clindamycin in the treatment of many of the conditions for which it was previously considered indicated, including acne, is being seriously reevaluated.


[Sebaceous filaments (author's transl)].

Sebaceous filaments are cylindrical tubes of whitish-yellowish color, which can be expressed from areas of the face rich in sebaceous follicles by pinching the skin or by the cyanoacrylat-technique. Sebaceous filaments are most commonly found in the centrofacial areas and the alae nasae in postpuberal individuals with large facial pores and seborrhea. Sebaceous filaments are composed of a skeleton of 10-30 horny cell layers which enclose a mixture of bacteria, sebaceous lipid, corneocyte fragments and one hair. Following the expression of the filament the follicle refills within 30 days. The various portions of sebaceous follicles (acro- and infrainfundibulum) and the follicular contents are presented at the light microscopial and ultrastructural level. Follicles containing sebaceous filaments have a conspicuous granular layer and no acanthosis. Sebaceous filaments should be differentiated from a microcomedo and trichostasis spinolosa. They are a common morphological variant of sebaceous follicles.


Cartilage of the patella. Topographical variation of glycosaminoglycan content in normal and fibrillated tissue.

The variation in the glycosaminoglycan content was studied at different sites of the patella, both where the cartilage was intact and where it showed varying degrees of fibrillation. It was found that when the cartilage surface was intact the glycosaminoglycan content was the same at the different sites of the patella. Local fibrillation always gave rise to a local lowering of fixed charge density, the magnitude of the latter correlating well with the visual assessment of the severity of the lesion. Even in the presence of severe lesions, if there was a site left on the patella where the cartilage was visually normal, its fixed charge density was also at a normal level. Thus, the depletion of glycosaminoglycans is a local phenomenon, limited to the area of fibrillation. The glycosaminoglycan content of normal cartilage is lower in the knee joint than in the hip. This fact, together with the existence of high pressure during load bearing, may be responsible for the greater frequency of destructive lesions affecting the cartilage of the patella compared with that of the hip.


Effects of implanted Doppler flowmeters on femoral vein autografts.

Thirteen femoral vein autografts were placed into the corresponding ipsilateral femoral arteries of 8 mongrel dogs. Cuff-type Doppler (ultrasonic) flowmeters were placed around six of the grafts. None of the vessels thrombosed. Blood flow velocities were measured in all vessels up until the time of sacrifice (mean 95 +/- 5 days after surgery) or accidental death (one dog, 49 days after surgery). The only case of graft failure was attributed to infection at the flowmeter site. With this single exception, the vein grafts exhibited uniformity in histological appearance from dog to dog. These data suggest that implantation of properly designed Doppler flow transducers may have clinical applications. This technique permits continuous or intermittent assessment of blood flow characteristics through a graft without additional trauma or cost to the patient. It is free of the many inherent disadvantages of chronically implanted electromagnetic flowmeters and may negate the need in some instances for followup angiographic studies.


Acceleration of tissue ingrowth on materials implanted in the heart.

A technique for accelerating the development of tissue layers on fabrics implanted in the bloodstream has been explored in dogs and monkeys. Endothelial cell seeding of the fabrics with cells derived from the endocardial surface of the atrium together with an autogenous plasma coating was shown to accelerate organization of fabric-covered devices implanted in the bloodstream of adult primates. At the same time, this technique appears simple and rapid enough to be practical in a clinical setting. The results suggest that this approach might be useful in accelerating the development of tissue layers on prosthetic valves implanted in the heart.


Immune-complex nephritis in bacterial endocarditis.

Glomerulonephritis developed in a 42-year-old man with subacute bacterial endocarditis caused by an alpha-hemolytic Streptococcus. The patient showed hypocomplementemia and an elevated serum rheumatoid factor titer. Immunofluorescence microscopy of a renal biopsy specimen demonstrated granular deposits of IgM and C3 in all glomeruli studied. With the indirect immunofluores(ence technique and specific antiserum, the antigen in glomerular deposits was observed to correspond to the organism found in the blood cultures. These findings can be taken as further evidence that the glomerulonephritis of subacute bacterial enoocarditis represent an immune-complex disease.


[Telesystolic mitral insufficiency with systolic click, mitral valve prolapse, and hypertrophic obstructive myocardiopathy].

There are several causes of the syndrome of "Late systolic murmur and mid-systolic click" due to mitral incompetence with ballooning of the valve, and, as numerous recent publications have shown, amongst them must be included abnormalities of left ventricular contraction. Seven cases have been studied by phonomechanocardiographic, cineangiographic, and haemodynamic methods, and analysis of the findings has shown that the abnormalities of contraction may be due to a cardiomyopathy, with a variable degree of left ventricular hypertrophy which is usually of patchy distribution, and leads to a certain degree of left intraventricular obstruction.


[Atresia of the pulmonary artery with intact interventricular septum. Apropos of 2 cases with prolonged course].

The authors report two cases of atresia of the pulmonary outflow with an intact interventricular septum; they are remarkable for their slow progression. In one patient the pulmonary perfusion was furnished by systemic arteries, while in the other it was by way of a patent ductus arteriosus. This second patient died following an attempted bi-cavo-pulmonary anastomosis. Such slow progression, which is the exception, is only possible if there is a substantial vicarious pulmonary circulation.


[Rupture of the heart in the acute phase of myocardial infarct. Anatomic-macroscopic study].

The data of the macroscopical-anatomical examination of 14 cases of cardiac rupture (10 women, 4 men) complicating acute myocardial infarction were compared with those obtained at autopsy, with the same protocol, in 31 cases of myocardial infarction which resulted in death before the 30th day after the onset. Many anatomical facts separated both groups from each other (size, aspect, limits of myocardial necrosis, state of the coronary arteries). Eventual surgical conclusions might be drawn from this study.


Prevention of vascular complications of diabetes by pancreatic islet transplantation.

Isolated pancreatic islets from Wistar-Lewis rats were transplanted into the liver of diabetic allogeneic recipients to assess ability to prevent diabetic renal and ophthalmic complications. At nine months, the diabetic animals without transplants showed significant increase in PAS-positive material in the renal glomerular mesangium and thickening of glomerular arterioles as compared with normal nondiabetic animals. New vessel formation was also significant in the retina and retinal capillary dilation. Animals in which diabetes had been corrected by early pancreatic islet transplantation were completely protected from these changes, showing no significant pathologic change when compared with normal animals.


Massive bleeding from a ruptured superior mesenteric artery aneurysm duodenum.

A traumatic false aneurysm of the superior mesenteric artery resulting from a gunshot wound five years previously, caused massive hemorrhage into the second portion of the duodenum. Dissection, resection, and end-to-end anastomosis was successful in controlling bleeding into the gastrointestinal tract, but immediate postoperative angiography showed a reappearance of the aneurysm, and three months later, it bled into the retroperitoneum. The patient underwent further resection and two subsequent reconstructions of the superior mesenteric artery, the first with a Dacron graft, which clotted, and the second with autologous saphenous vein, which was successful. Three years later, the patient is well. The case shows that adequate reconstruction of an arterial injury is best performed immediately after it is diagnosed.


Closure of massive abdominal wall defects in adults.

Large full-thickness abdominal wall defects may be satisfactorily closed with the temporary use of prosthetic mesh. Within two weeks after placing silastic mesh directly over exposed bowel, a membrane forms below the mesh. When the membrane thickens, central eliptical portions of the mesh are progressively excised, diminishing the size of the defect. Eventually, the mesh may be removed and the defect closed primarily or repaired with permanent prosthetic mesh.


"Karshi" virus, a new flavivirus (Togaviridae) isolated from Ornithodoros papillipes (Birula, 1895) ticks in Uzbek S.S.R.

Three identical strains of an arbovirus were isolated from 475 Ornithodoros papillipes ticks collected in June, 1972, in burrows of the great gerbil (Rhombomys opimus Licht., 1882) in the environs of Beshkent, Karshinsk steppe, Uzbek S.S.R. The isolate was found to range among flaviviruses. Complement-fixation, agar diffusion precipitation and neutralization tests is tissue culture and mice indicated a one-way antigenic relationship between the isolate and West Nile virus. However, the pattern of differences between them made it possible to consider the isolated agent as a new virus, "Karshi" virus. The results of electron microscopic studies of this virus are presented.


[Histochemical study of carbonic anhydrase and HCO3(-)-stimulated adenosine triphosphatase in the rat stomach during hydrochloric acid secretion].

By means of histochemical methods it was established that carboanhydrase of the parietal cells of fundal glands and HCO-3 stimulated ATP-ase of the rat's gastric mucosa capillaries disposed next to the parietal cells were activated by food and histamine. The obtained data confirm the idea of the multicellular functional essembly sustaining HCL secretion (R. I. Salganik, 1974). Should gastrin induce the formation of histamine in endocrinous cells and the histamine activate carboanhydrase in parietal cells, our data confirm the supposition that HCO-3-ions stimulate ATP-ase sustaining the exchange between HCO-3-cells and C1- of blood to form HCl in the endothelial cells of blood capillaries adjacent to the parietal cells.


[Autoradiographic and histochemical study of the intestinal epithelium of the Baltic lamprey].

The intestinal epithelium of the Baltic lamprey and its larva was studied. Glandular cells and absorbing cells simultaneously capable to synthesize polysaccharides were found histochemically in the composition of the epithelial layer. The cranial zone where glandular cells analogous to the cells of the pancreas were concentrated was revealed in the medial intestine of the larva. The rest of the intestine was devoid of specialized glandular cells. Using H3-thymidine as a precursor it was shown that in the cranial zone of the intestine the cambial cells were scattered diffusely throughout the whole epithelial layer and in other portions of the medial intestine the cambial zone was distinctly seen in the lateral portions of the intestine (the area of the fornix) where labelled nuclei were formed and mitoses took place. After injection of H3-thymidine poor incorporation of the isotope was found in the nuclei of solitary cells of some adult lampreys going to spawning. Uneven incorporation of S35-methyonine, used as a precursor, in the epithelium of the intestine and the liver of the adult lamprey was shown.


[Cellulomembranous formations as the main stroma of the hepatic lobe in mammals].

Thick (25-30 mu) sections of the fresh human, rabbit and rat liver were dismembered by vibrating in saline and the connective-tissue honeycomb-pannicular formations (HPF) were revealed. While being devoid of hepatocytes they correspond to the surface of the cross section of the lobule in a number of cases both by the form and by the size. Silver impregnation stains the HPF in yellow and the argirophilic fibres in black. Under natural conditions hepatocytes are disposed on the HPF with the wide basal side forming a one-cell-high layer with its total body and the free opposite apical surface.


[Stomach polyps in simians at the Sukhumi nursery].

Polyp-like changes in the mucous membrane of the stomach were noted in monkeys of the simian nursery in Sukhumi (100 cases). In 6 baboon hamadryads, in 4 Stum-tailed macaques and in one macaco rhesus they were diagnosed as the so-called polypous gastritis. In 5 Stum-tailed macaques there were noted gigantic folds of the pylorus. Of 84 macacos in 61 animals there was one polyp and in 23 macaques--2 and more polyps. Incidence of polyps among local monkeys was 0.48% in macaques rhesus and 2.3% in Stum-tailed macaques. Among imported monkeys the incidence of polyps was in macaques rhesus--0,31% and in Stum-tailed macaques--9,2%. Polyps in monkeys are considered as disregenatory formations, occasionally associated with parasitizing of helminths. In contrast to man, polyps in monkeys are not considered as precancer processes.


[Histoenzymatic studies and internal irradiation. III. Histoenzymatic changes of the kidney treated with chloromeridrin Hg 197].

The histochemical behaviour of alkaline phosphatase, adenosintriphosphatase, acid phosphatase and acetylglucosaminidase activities was studied in rat kidney treated with Chloromeridrin Hg. In these experimental conditions it was found that the nephrocytes in the proximal convoluted tubule present changes in the enzymatic activities examined, generally proportional to the doses employed. With lower doses of radionuclides, the histoenzymatic changes have a local character and are completely reversible after a month. With higher doses they take on a more extensive character and persis to some extent one month after treatment. These findings suggesti that Hg could be used clinically with due precautions.


[A morphohistochemical study of the embryotropic action of steroids with androgenic properties].

Morphohistochemical study of an embryotoxic and teratogenic action of acetate of androstenolone, acetate of 16-dehydropregnenolone, and methyltestosterone applied dayly to the skin of white rats during the entire course of gestation was carried out. A marked embryotoxic effect of acetate of androstenolone has been established. The teratogenic effect of the agents under study manifested itself in impairment of the processes of differentiation of structural elements of organs and tissues, or in rough underdevelopment of foetuses on the whole (following the exposure to acetate of androstenolone). In addition, a decrease in contents of nucleic acids and proteins in tissues, as well as some disorders of the carbohydrate metabolism in different organs and tissues were noted. The authors recommend to use histological and histochemical methods in investigations of embryotropic action of low doses of steroids.


[Congenital heart defects in persons of advanced and old age].

The article presents data on 7 sectional observations on congenital heart defects in elderly and old persons (57 to 75 years). An open oval window with the functioning valve was detected in 6 cases, completely non-obliterated oval window--in one case. The correct diagnosis had not been made when the patients were alive. This can be easily explained due to the difficulties of diagnosing, since no clinical manifestations of the defect were noted for a long time. In all cases death was caused by chronic cardiovascular insufficiency.


[Photocoagulation of senile macular degeneration. (Critical analysis of the results obtained in 66 cases)].

The article is a critical study of visual results obtained by means of photocoagulation in 66 cases of senile macular degeneration with a follow up from 3 months up to 45 months. The author believes that an improvement of the visual acuity of 0,1 is not a reliable criteria for evaluation of the results. She takes as true good results only the cases in which reading is possible after treatment (visual acuity greater than or equal to 0,7 Parinaud 3). Using that criteria the percentage of true sucess is only of 32,5 p. 100 for the cases treated since over one year. That percentage is low but it seems enough to justify the treatment since only 3,4 p. 100 of the non treated cases keep usefull visual acuity after one year. Besides, review of the causes of sucess and failures leads to feel that the results should be improved in the future by an earlier treatment, a better selection of the indications and a more accurate technique.


[Retinal detachment caused by disinsertion of the ora serrata. Study of 100 cases treated by various methods].

A presentation of 100 cases of retinal detachment caused by retinal disinsertion reviewed over 25 years. The overall sucess rate (84 per cent) improves to 95 per cent with the introduction of cryotherapy associated with Lincoff sponges.


[Highly hydrophilic soft lenses. Optic indications for permanent wearing and adaptation technic].

After the indications of the various contact prostheses are briefly reviewed, the interest of continuous wearing of optical hydrophilic soft lenses is emphasized. Aphakia, high ametropis and anisometropia are the main indications. Yet, continous wearing should be recommended only to patients who have difficulty with contact lens manipulation. The patient will be admitted twice in hospital for the fitting and cared for twice a day which permits to get over the difficulty of the first two nights. From the evaluation os the fitting of 33 eyes, the advantages, disadvantages, failures and complications of such a technique are discussed.


[Spatial value of the fovea in young children].

After defining physiological fixation of the fovea and relating our knowledge of its normal development in the context of spatial perception, we have reviewed the pathological adaptations encountered in strabismus. Out of all the clinical examinations that are possible in very young children and which enable sensory disturbances to be revealed, the examination of fixation appears to be simple and dependable, sometimes well before the appreciation of the comparaison of visual acuity of the two eyes. Amblyopia can be suspected using this method in cases of poor foveal fixation when compared with the other eye, and it enables treatment to be instituted and controlled all the more efficiently since therapy in an early stage can lead to a rapid recovery and maintenance of normal development.


[Intraocular and cerebral reticular sarcoma].

An anatomo-clinical study is presented of a reticulum cell sarcoma (or lymphosarcoma), limited to the eye-ball and the brain. The eye disease developed as a chronic, diffused hypertensive uveitis. The diagnosis of the nature of the brain tumour was made by cytological study of the cerebro-spinal fluid.


[Vertical vergences. I. Physiological and pathological aspects].

The vertical vergences are rather weak physiological conjugate movements of the eyes. When the ocular axes approach each other or deviate, a vertical convergence or divergence occurs. These reflex movements are evoked either by visual stimuli (fusional vergence) or by labyrinthine stimuli. In pathological situations vertical vergences may become evident in permanent or alternating hyperphorias, in the strabismus occurring in the Hertwig-Magendie syndrome, in see-saw nystagmus and in labyrinthine lesions (such as Meniere's disease, after labyrinthectomy and after section of the VIIIth nerve).


[Atypical conjunctival and tonsillar locations of malacoplakia].

Conjunctival and tonsillar sites for malakoplakia have never been previously described. The diagnosis in these presented cases has only been arrived at after elimination of mycosis and parasitic disease. The aetiology remains unknown and the pathophysiology is discussed.


[Scanning microscopy aspects of the corneal endothelium in disciform keratitis and graft rejection].

Scanning electron microscopic study of corneal endothelium in two cases of corneal disease. In one case of herpetic keratitis with stromal oedema and anterior uveitis an important cellular reaction is found with different cells forming a retrocorneal membrane. In a case of graft rejection there are two different aspects. On somes places there is an inflammatory reaction with lymphocytes and macrophages. The main surface of the graft is covered with indifferenciated cells whose origine is probably the receiver's endothelium.


[Areolar atrophy of the macula].

The article is a general review of central areolar choroidal dystrophy based on 24 cases, some of them followed from one year up to six years. Two major points are discussed: the etiology and the natural course. The disease is believed by the author not to be an etiological entity for, if it can occur as a primary maculopathy, it is more often the ultimate stage of another heredo macular degeneration. The visual prognosis depends more upon the location of the lesion than upon its size. Of course the visual prognosis is poor when the atrophy involves the center of the macula, but it is good, at least during several years, when the very center of the fovea is spared off.


[Drachman's "ophthalmoplegia plus" or Kearns and Shy syndrome. Apropos of 2 cases with mitochondrial abnormality ultrastructurally demonstrated in the muscle].

Two typical cases of the Kearns and Shy syndrome are reported. Some of the authors have previously published observations on simple ocular myopathy and oculo-pharyngeal dystrophy associated with abnormalities of the mitochrondria in skeletal muscle cells. This disease, which is still called "ophthalmoplegia plus", combines a progressive external ophthalmoplegia, muscular defects and varied neurological signs with other symptoms particularly retinal, endocrine and cardiac. Histo-enzymological and ultra-structural studied of a fragment of skeletal muscle confirm the presence of mitochondrial anomalies.


[Urbach-Wiethe syndrome].

The "Urbach-Wiethe syndrom" is an hereditary disease which start during early childhood, distinguishable by a lipoglycoproteinosis which affects the skin, mucosae and also the eyes, with cyst formations in the lid's marginal, drusen of Bruch's membrane. Corneal opacities, and glaucoma seen to be rarer.


["Implicit time". Practical and theoretical aspects].

52 normal subjects were studied as control for our "Ganzfeld" method of E.R.G. Separately 132 patients with different retinopathies; inflammatory and degenerative (or dystrophic) were studied and results compared and discussed. It seems that the amplitude is involved - diminished - in some retinopathies, but implicit time only when widespead alteration of neuro-epithelim accured.


[Electron microscopic study of the corneal endothelium in 2 cases of keratitis. Herpetic disciform keratitis. Neuroparalystic keratitis with dry keratitis].

Study of corneal endothelium by scanning and transmission electron microscopy in two cases of corneal disease. In one case of herpetic keratitis with stromal oedema, there is no cellular reaction. The endothelium is damaged with cellular necrosis and nucleus irregularity. Intercellular junctions are abnormal. With TEM it is possible to say that there are two layers of cells on some places with cellular necrosis. In one case of corneal dryness with lesions of corneal anaesthesia the cells are very damaged and a retrocorneal membrane if formed by many layers of cells. The intercellular junctions are almost normal.


Frequency of incidence of retina detachment in the French population. Percentage of bilateral detachment.

An inquiry conducted with French ophthalmologists shows an incidence of retinal detachment in the French population of about 8 in 100000, 13 to 14p. 100 of the cases were bilateral.


[Influence of surgical technic in cataract operation. (Postoperative astigmatism, type of iridectomy)].

The authors have made a statistical study of the influence of surgical technique on the anatomical (astigmatism) and functional results in cataract surgery. They have taken into consideration whether the incision is made under a conjunctival flap or not, with a keratome or Gillette blade, with a sector or peripheral iridectomy. Their conclusions are that when performed by the same surgeon the different surgical techniques do not give rise to significant variations in astigmatism or in the eventual functional result.


[Current problems posed by carotid-cavernous arteriovenous fistula].

The authors discuss the problems posed by carotico-cavernous fistulae. New radiological techniques enable a more precise diagnosis, a haemodynamic approach and the therapeutic solutions are able to avoid all surgical intervention.


[Intraocular complications following Custodis-Lincoff operation].

This investigation is based on 262 cases of retinal detachment treated with episcleral silastic sponge implants and cryopexy. Anatomical restoration of the retina after one operation or more was successful in 89 percent. Drainage of subretinal fluid was carried out in 52 percent of the cases. Supplementary light-coagulation 3 or 4 weeks after the operation was applied in 43 cases (17 percent) in order to seal off retinal holes on the buckle due to inadequate chorioretinal adhesion following cryopexy. Insufficient adhesion was directly related to the retinal elevation in the area of the tear. Chorioretinal haemorrhages in the group without release of subretinal fluid were caused by the following factors: Repeated cryo-application in the same place, application of the probe on the open part of the tear instead of around the tear, sponge-fixation in the immediate area to vortex veins, pressure exerted by the sponge on choroidal and retinal vessels, particularly in persons of advanced age. Local haze of the vitreous corresponding to the location of the cryp-application was directly related to the number of applications and the position of the tear. Vitreous haze was more frequent where the hole was situated towards the ciliary body. Pigment migration was observed in 9 percent of the cases. It should be noted that this complication was also encountered preoperatively in a group amounting to 4 percent of the total number of cases after padding of the eyes and absorption of subretinal fluid. Such cases should be distinguished from those of postoperative occurrence of pigment migration. Detachment of the choroid happened more often in the group in which subretinal fluid was released. In this group expulsive haemorrhage also occurred, which, apart from the choroidal detachment, resulted, immediately upon drainage of subretinal fluid, in high intracular pressure. Macular puckering was noticed in 5 cases (2,7 percent). In 4 out of the 5 cases with this complication, the tear was located towards the posterior pole and sponge fixation was radial.


[Vitelliform degeneration of the macula].

Macular vitelliform degeneration is an hereditary affection, with autosomal dominan transmission. It is probably congenital. Three phases in the evolution of lesions: I The "fried eggs" aspect. II Various ophthalmologic aspects: mixed egg, pseudo-hypopion, retractile form. During these first two phases, the yellowish vitelline substance only may extend in macular region, especially downards. III The atrophic phase. Visula acuity remains strangely good, especially during the first two phases. Nevertheless, the visual function study, especially colour vision and profile perimetry, elecites a precocious suffereance of macular cones, associated to fluorographic alteration of pigmentary epithelium in phases II and III. Actually, these lesions are mostly situated in perifoveolar area, respecting the foveola, which explains conservation of good vision. The electro-oculogram is deeply modified in most cases. The pathogenesis of this affection remains unexplained, but the evolution of lesions both in pigmentary epithelium and neuro-epithelium enables to think that vitellin substance lays between these two layers.


[Histology and function of the cryopreserved corneal endothelium].

This work consists of a histological study of cryopreserved corneal endothelium before and after perfusion, and of measurements of the corneal thickness during perfusion. 1) Histoligical study: a) After 7 hours of perfusion, the endothelium of fresh corneas is unchanged. b) The preserving solutions used for freezing do not modify the histological structure of the endothelium. c) All the freezing and thawing processes described in this paper substantially alter the histological structure of the endothelium. Latent alterations are revealed during perfusion. 2) Pachymetric study: a) In the experimental conditions described, the fresh corneas keep their normal thickness for 7 hours of perfusion. b) The preserving solutions do not modify this property. c) After freezing and thawing the thickness of the perfused cornea increases rapidly. The thickness of the perfused cornea appears more slowly under the following conditions: 33 to 66 p. 100 of serum in the preserving solution, volume less than 1 ml; eutectic point between - 4 and - 6 degrees C; the duration of the plateau less than 4 min. speed of freezing after the plateau about 5 degrees C/min.


[Organotypic culture of the rabbit cornea. Evaluation of its morphologic criteria].

A report of a study on the cellular and tissue morphology of organotypic cultures of rabbit cornea using a method conforming to physiological conditions. The results demonstrate that in the first few hours there exist structural changes in the tissues as well as on ordinary histology, scanning and electron microscopy. These affect the endothelium primarily, whereas the keratocytes and epithelium seem to be more resistant, the latter having the tendency to invade the surfaces of the explant and to transform itself into fibroblastic cells. Certain reservations should therefore be expressed about the use of these explants, whether they are intended to preserve pathological corneas of different origin, or to be used in transplants.


Efficacy of Linco-Spectin water medication on Mycoplasma synoviae Airsacculitis in broilers.

Three trials were conducted to evaluate the efficacy of Linco-Spectin (LS) water medication on Mycoplasma synoviae (MS) air-sacculitis in broilers under controlled experimental conditions. Day-old chicks were vaccinated against infectious bronchitis and Newcastle disease virus and exposed to a broth culture of MS by the respiratory route. In each trial, one-half of the flock was treated with 2 g of LS per gallon of drinking water for the first five days of life, and the other half was kept as a control. At two and eight weeks postinoculation (PI) birds were weighted individually and examined serologically, culturally, and grossly for MS airsacculitis. Linco-Spectin water medication was effective in controlling MS airsacculitis in broilers.


Organization of ground substance proteoglycans in normal and osteoarthritic knee cartilage.

A study of the organization of proteoglycans in articular cartilage indicates that nonaggregated proteoglycans existed in larger numbers in osteoarthritic than in normal cartilage and that proteoglycan aggregates in arthritic cartilage were smaller than normal. After dissociation from hyaluronic acid and tissue glycoproteins, no difference in hydrodynamic size of disaggregated proteoglycans was noted, but chondroitin sulfate chains of those from diseased cartilage were shorter than normal. The data suggest that there is a defect in proteoglycan aggregation in osteoarthritic cartilage which could be of pathogenetic significance.


The natural history of rheumatic aortic regurgitation and the indications for surgery.

A detailed review was made of 180 patients with severe aortic regurgitation of rheumatic origin. Of these patients, 110 underwent aortic valve replacement. Thirty-nine clinical and haemodynamic factors were studied in an attempt to define those associated with (1) death before surgery, (2) a higher incidence of complications and hospital mortality after surgery, and (3) an unsatisfactory longer-term result of surgery. Only heart failure, radiographic heart size, left ventricular hypertrophy, and ventricular premature beats were associated with death before surgery. No factor predisposed to surgical complications and only preoperative factors associated with an unfavourable result after surgery were advanced heart failure, cardiomyopathy, extreme cardiomegaly, and ventricular premature beats. It is concluded that the indications for operation are: a cardiothoracic ratio of greater than 0-60, or a history of heart failure combined with electrocardiographic evidence of extreme left ventricular hypertrophy. Operation may be safely postponed if these indications are not met, though the presence of ventricular extrasystoles or evidence of independent myocardial disease are further factors which should influence the decision.


Regression of primary pulmonary hypertension.

A girl who presented in childhood with advanced primary pulmonary hypertension and whose condition later improved is described. This is the first time to our knowledge that documented regression of the disease has been reported.


The effect of manipulation of reticuloendothelial system activity on glomerular deposition of aggregated protein and immune complexes in two different strains of mice.

Glomerular uptake of intravenously administered aggregated albumen or immune complexes in mice appears to be inversely related to the activity of the reticuloendothelial system (RES). Stimulation of RES activity diminishes the amount of material appearing in the glomerulus whereas RES blockade enhances glomerular uptake. The possible relevance of these observations to experimental models of immune complex disease is discussed.


Anaerobic transport of amino acids coupled to the glycerol-3-phosphate-fumarate oxidoreductase system in a cytochrome-deficient mutant of Escherichia coli.

The uptake of proline and glutamine by cytochrome-deficient cells of Escherichia coli SASX76 grown aerobically on glucose or anaerobically on pyruvate was stimulated by these two substrates. Pyruvate could not stimulate transport in the glucose-grown cells. Uptake of these amino acids energized by glucose was inhibited by inhibitors of the Ca2+, Mg2+-stimulated ATPase such as DCCD, pyrophosphate, and azide, and by the uncouplers CCCP and 2,4-dinitrophenol. Glycerol (or glycerol 3-phosphate) in the presence of fumarate stimulated the transport of proline and glutamine under anaerobic conditions in cytochrome-deficient cells but not in membrane vesicles prepared from these cells although glycerol 3-phosphate-fumarate oxidoreductase activity could be demonstrated in the vesicle preparation. In contrast, in vesicles prepared from cytochrome-containing cells of E. coli SASX76 amino acid transport was energized under anaerobic conditions by this system. Inhibitors of the Ca2+, Mg2+-activated ATPase and uncoupling agents inhibited the uptake of proline and glutamine in cytochrome-deficient cells dependent on the glycerol-fumarate oxidoreductase system. Ferricyanide could replace fumarate as an electron acceptor to permit transport of phenylalanine in cytochrome-deficient or cytochrome-containing cells under anaerobic conditions. It is concluded that in cytochrome-deficient cells using glucose, pyruvate, or glycerol in the presence of fumarate, transport of both proline and glutamine under under anaerobic conditions is energized by ATP through the Ca2+, Mg2+-activated ATPase. In cytochrome-containing cells under anaerobic conditions electron transfer between glycerol and fumarate can also drive transport of these amino acids.


Gaps in DNA synthesized by ultraviolet light-irradiated WI38 human cells.

DNA replication in ultraviolet-irradiated human cells was examined by treatment of the extracted DNA with a single-strand specific endonuclease from Neurospora crassa. WI38 cells were uniformly labeled with 32Pi for two generations before irradiation and then labeled with [3H]thymidine after irradiation. The isolated DNA was sedimented in neutral sucrose gradients after incubation with the endonuclease. The endonuclease treatment had no effect on the sedimentation profiles of either [32P]DNA or [3H]DNA from unirradiated control cultures. The endonuclease treatment also did not significantly alter the profile of [32P]DNA from irradiated cultures but did introduce breaks in the 3H pulse-labeled DNA synthesized after irradiation. These results indicate that DNA synthesis after ultraviolet irradiation proceeds in such fashion that gaps are formed along the newly made strand, leaving regions of single strandness in template DNA. As replication proceeds these gaps disappear and 2 h after irradiation (100-250 ergs/mm2) they are barely detectable by the endonuclease assay.


"Action potentials" in Neurospora crassa, a mycelial fungus.

Occasional spontaneous "action potentials" are found in mature hyphae of the fungus Neurospora crassa. They can arise either from low-level sinusoidal oscillations of the membrane potential or from a linear slow depolarization which accelerates into a rapid upstroke at a voltage 5-20 mV depolarized from the normal resting potential (near-180 mV). The "action potentials" are long-lasting, 1-2 min and at the peak reach a membrane potential near-40 mV. A 2-to 8-fold increase of membrane conductance accompanies the main depolarization, but a slight decrease of membrane conductance occurs during the slow depolarization. Two plausible mechanisms for the phenomenon are (a) periodic increases of membrane permeability to inorganic ions, particularly H+ or Cl- and (b) periodic decreases in activity of the major electrogenic pump (H+) or the Neurospora membrane, coupled with a nonlinear (inverse signoid) current-boltage relationship. Identification of action potential-like disturbances in fungi means that such behavior has now been found in all major biologic taxa which have been probed with suitable electrodes. As yet there is no obvious function for the events in fungi.


Comparison of the physicochemical properties of fragment D derivatives of fibrinogen and fragment D-D of cross-linked fibrin.

The molecular weight of Fragment D derivatives obtained from plasmic digests of fibrinogen and cross-linked fibrin was determined by equilibrium sedimentation and compared with the summated molecular weight of their polypeptide chains observed after electrophoresis of reduced protein in sodium dodecyl sulfate polyacrylamide gels. The measured molecular weight of Fragment D (Stage 2) of fibrinogen is 103 500, which is compatible with a molecule containing only one each of the Aalpha (13 000), Bbeta (43 000) and gamma (39 000) chain remnants. Fragment D-D of cross-linked fibrin has a molecular weight of 189 000, compatible with a molecule containing one isopeptide-bound gamma-gamma chain (80 000) and two each of Bbeta (43 000) and Aalpha (13 000) chain remnants. The NH2-terminal amino acid residues of the Fragment D derivatives were measured quantitatively using a thioacetic-thioglycolic acid method, and molar quantities were calculated on the basis of the molecular weights determined by equilibrium sedimentation. Fragment D preparations obtained from Stage 2 and Stage 3 digests of fibrinogen have 3 mol of NH2-terminal amino acids per molecule, while Fragment D-D has seven. These data support the view that two Fragment D molecules, each of three polypeptide chains, are derived by plasmic degradation from each fibrinogen molecule, and that an isopeptide-bound, six chain Fragment D-D molecule is released from cross-linked fibrin by plasmin. Equlibrium sedimentation measurement of the molecular weights of Fragment X (Stage 1 and Stage 2) and Fragment Y are 265 000 and 148 000, respectively. These values are compatible with asymmetric cleavages of Fragment X to Fragments Y and D (Stage 2), and of Fragment Y to Fragments D (Stage 2) and E, and with a fibrinogen model in which the two halves are joined by disulfide bonds only in the amino-terminal regions.


Diphasic transformations of F-actin. Effects of urea and MgCl2 on F-actin.

Asakura, Taniguchi and Oosawa [1]proposed that muscle actin polymer under sonic vibration is in a different state from that of the ordinary double stranded helical structure (F-actin), characterised by partially interrupted structures of F-actin, a state of "f-actin". In order to confirm different states for actin polymers [1, 2], physicochemical studies were made by measurements of viscosity, flow birefringence, electric birefringence, fluorescence, electron microscopy, quasielastic light scattering and ATP splitting. The following results were obtained. (1) F-actin polymers can undergo two processes of depolymerization upon treatment with urea and various salts as judged by measurements of flow birefringence and viscosity: one is a rapid process in a solution containing K+ or Ca2+ and urea; the other is a slow process following a brief rapid one in a solution containing Mg2+ and urea. (2) In the presence of Mg2+ and a suitable concentration of urea, F-actin (FMU-actin) appeared to exhibit different properties than ordinary F-actin; it had lower viscosity and lower flow birefringence and it had on the whole a more flexible polymer structure, also judging from experiments of quasielastic light scattering, electric birefringence. The different structure was confirmed directly be electron microscopic observation. The aromatic side chains of FMU-actin were also more mobile than those of F-actin judging from fluorescence measurements. The transformation between F-actin and FMU-actin was reversible. (3) The state of FMU-actin polymers was also characterized by ATP splitting; FMU-actin split about one mole of ATP into ADP and inorganic phosphate per mole of actin monomer at room temperature, where F-actin did not. A molar excess of Mg2+ with respect to actin monomer at room temperature, where F-actin did not. A molar excess of Mg2+ with respect to actin monomer is required for ATP splitting. F-actin in solutions containing K+ or Ca2+ and urea did not split ATP. FMU-actin activated on Mg-ATP-ase of myosin at nearly the same rate as that of F-actin. (4) We have postulated a flexible filament model (f-actin). The relationships between the structure of f-actin and its functional role for force generation during contraction are discussed.


Cleavage of thrombosthenin A by thrombin. Evidence for the existence of two types of bovine platelet actin.

Bovin platelet actin prepared by Spudich's method (Spudich, J. A. (1972) Cold Spring Harbor Symp. Quant. Biol. 27, 585-594) separated into two peaks on a Sephadex G-200 column. The actin of both peaks had a mol. wt. of 42 000 on sodium dodecyl sulfate-polyacrylamide gel and activated myosin ATPase, although in a quantitatively different manner. Actin eluted in the first peak (probably an oligomeric form) was not polymerized in 2 mM MgCl2 and 0.05 M KCl, while that of the second peak went through normal G-F transformation. If CaATP was present in the incubation mixture neither actin was attacked by thrombin. However, if EDTA was added, thrombin split G-actins and the pattern of cleavage was the same as that found for muscle actin in our earlier studies, i.e. the final split products were two actinopeptides and two larger fragments of 26 500 and 11 000 daltons. It is suggested that the possible attraction of membrane-associated platelet actin for thrombin may have an importance in thrombin-induced platelet aggregation.


The heterogeneity of dermatan sulfate and heparan sulfate in rat liver and a shift in the glycosaminoglycan contents in carbon tetrachloride-damaged liver.

The glycosaminoglycan of rat liver can be separated into five distinct fractions; a hyaluronic acid fraction, a heparan sulfate fraction with a molar ratio of sulfate to hexosamine (S/HexN) around 0.7, a heparan sulfate fraction with a S/HexN ratio around 1.4, a dermatan sulfate fraction with a S/HexN ratio near unity, and a dermatan sulfate fraction with a S/HexN ratio around 1.3. Enzymatic analysis of the two dermatan sulfate fractions indicates that they differ significantly in that the high sulfated fraction contains relatively more N-acetylgalactosamine 4,6-bissulfate units (about 26% of the total hexosamine). In experimental injury produced by carbon tetrachloride, the low sulfated fraction increases as much as 9-fold on a dry weight basis, bearing no linear relationship to the amount of the high sulfated fraction which increases only 2-fold. A significant shift is also observed in the levels of the two heparan sulfate fractions. In this case, however, the high sulfated fraction shows a much more pronounced increase than does the low sulfated fraction. On the basis of these observations, it is suggested that for each of the dermatan sulfate and heparan sulfate classes there are at least two pools, distinguished by sulfation degree and perhaps by turnover rate and physiological function.


Glycolipid glycosyl transferases of a hamster cell line in culture. II. Subcellular distribution and the effect of culture age and density.

The activities of two galactosyl transferases catalysing the formation of di- and tri-glycosyl ceramides in NIL-2 hamster cells have been studied with respect to culture age and density, subcellular distribution, and transformation of cells by virus. The activity of the transferases was found to increase considerably as culture density increased, although maximal activities were found before appreciable cell contact occurred. The highest transferase activities were found in the endoplasmic reticulum. Virus transformation reduces the activity of the transferase catalysing triglycosyl ceramide synthesis, while the transferase catalysing diglycosyl ceramide synthesis is slightly increased. There is no evidence that the transformed cells produce a dialysable soluble inhibitor of transferase activities.


Na+-dependent phosphorylation of the rat brain (Na+ + K+)-ATPase. Possible non-equivalent activation sites for Na+.

The steady state levels of Na+-dependent phosphoenzyme (E-P) in the (Na+ + K+)-ATPase (EC 3.6.1.3) of rat brain, obtained from a time course study of phosphoenzyme formation at 4 degrees C, were dependent on the concentration of Na+ in the reaction and were maximal in the presence of 64 mM Na+. The plot of phosphoenzyme vs. Na+ concentration gave a curve which on conversion to a double reciprocal plot (1/E-P vs. 1/Na+) gave a line with two breaks, yielding apparently three linear segments. This may be taken to indicate the presence of multiple Na+ sites for the formation of the phosphoenzyme. To test this hypothesis further, the following approach was taken. By making the assumption that the phosphoenzyme may represent bound Na+, it was possible to subject the data to rigorous multiple-site analysis by utilizing steady-state binding equations described by Klotz and Hunston (1971) (Biochemistry 10, 3065-3069), and by Scatchard (1949) (Ann. N.Y. Acad. Sci. 51, 660-672). The analysis of the data by these methods suggests that there may be three non-equivalent Na+ activation sites for the formation of Na+-dependent phosphoenzyme in the (Na+ + K+)-ATPase. The estimated intrinsic association constants (Ka) for activation by Na+ at each of the three sites were 3.4, 0.295, and 0.025 mM-1, respectively.


Purification of protoplast-secreted acid phosphatase from baker's yeast. Effect on adenosine triphosphatase activity.

In order to examine acid phosphatase (EC 3.1.3.2) and ATPase (EC 3.6.1.3) activities of baker's yeast (pH optimum 3.5) a protoplast-secreted enzyme preparation was purified and some physical and chemical properties were studied. Three protein fractions containing ATPase and acid phosphatase activities, in the same ratio as the initial preparation, were separated by ion-exchange chromatography. The first fraction which had the highest protein content yielded a homogeneous preparation after Sepharose 4B chromatography and was used in further studies. An attempt to estimate molecular weight of this protein was made. Attempts to separate acid phosphatase and ATPase activities by ion-exchange chromatography, gel filtration, isoelectric focusing and sucrose density gradient centrifugation have been unsuccessful. Both activities behaved the same way to heat and urea denaturation. These results suggest that the two activities are associated with the same protein molecule.


A reexamination of the postulated charge transfer interactions at the active site of the enzyme rhodanese.

Spectral and kinetic studies of the interaction of N-methylnicotinamide chloride and nicotinamide with the enzyme thiosulphate sulphurtransferase (thiosulphate: cyanide sulfurtransferase, EC 2.8.1.1) (also known as rhodanese) have been performed and compared with previous inhibition data obtained with N-1-(4-pyridyl)pyridinium chloride (NPP). Like NPP both N-methylnicotinamide chloride and nicotinamide are competitive inhibitors of rhodanese with respect to the substrate thiosulfate. Rhodanese binding of N-methylnicotinamide chloride gives rise to no charge transfer absorbtion band. In addition, the free energy of interaction (deltaG0) of NPP with rhodanese is approximately equal to the sum of the individual deltaG0 values of MNA and NA. These compounds are analogous to the two halves of the NPP structure. We conclude that NPP and N-methylnicotinamide chloride are not bound via a charge transfer mechanism. The major stabilizing influence appears to be an ionic interaction with an anionic enzyme site with accessory apolar stabilization. It is postulated that the ionized active site sulfhydryl group in rhodanese could provide the ionic site.


Effect of ozone on erythrocyte membrane adenosine triphosphatase.

Human erythrocyte membrane fragments were exposed to O3 over varying lengths of time. Ozone was found to have a deleterious effect on the ouabainsensitive ATPase (EC 3.6.1.3) in the membrane fragments. After 1 min of exposure to O3, which was generated at a rate of 4.0 mumol/min, ouabain-sensitive ATPase activity decreased to 26% of the control. Ouabain-insensitive ATPase was found to be unaffected by O3 exposure under the test conditions. Additions of ascorbic acid or cysteine, prior to O3 exposure, partially protected the enzyme from inactivation. However, the inactivating effect of O3 could not be reversed by addition of either ascorbic acid or cysteine after exposure. Superoxide dismutase or catalase did not afford significant protection. The enzyme could not be protected by Ellman's reagent. The inactivating effect of O3 on the ouabain-sensitive ATPase was also demonstrated in exposure of intact erythrocytes. No detectable change was observed in glycolytic activity in the hemolysate prepared from O3-treated erythrocytes, however. It was postulated that inactivation of the membrane ATPase by O3 may be responsible for the destructive effect of O3 on the red cell.


Studies on photophosphorylation utilizing methylene diphosphonate analogs of ADP and ATP.

Spinach chloroplasts were able to photophosphorylate the ADP analog alpha,beta-methylene adenosine 5'-diphosphate (AOPCP). Phosphorylation of AOPCP was catalyzed by chloroplasts that were washed or dialyzed to remove free endogenous nucleotides. In the presence of glucose, hexokinase, AOPCP and 32Pi, the 32P label was incorporated into alpha,beta-methylene adenosine 5'-triphosphate (AOPCPOP). In contrast to photophosphorylation of AOPCP, the ATP analog AOPCPOP was a poor substrate for the ATP-Pi exchange reaction and its hydrolysis was neither stimulated by light and dithiothreitol nor inhibited by Dio-9. Photophosphorylation of AOPCP was inhibited by the alpha,beta- and beta,gamma-substituted methylene analogs of ATP, while phosphorylation of ADP was unaffected by them. The ATP-Pi exchange was also unaffected by both ATP analogs, while the weak AOPCPOP-Pi exchange was inhibited by the beta,gamma-methylene analog of ATP. Direct interaction of methylene analogs with the chloroplast coupling factor ATPase was indicated by the enzymatic hydrolysis of AOPCPOP on polyacrylamide gels.


Pig heart mitochondrial ATPase : properties of purified and membrane-bound enzyme. Effects of flavonoids.

Soluble ATPase (F1) has been purified from pig heart mitochondria. The purified enzyme had a high specific activity and was homogeneous as checked by ultracentrifugation and electrofocusing. It could be dissociated into subunits by cold-treatment or sodium dodecyl sulfate denaturation. The molecular weights of the two major and three minor subunits could be estimated by sodium dodecyl sulfate gel electrophoresis. The native enzyme had an isoelectric point of 5.2 while the cold-denatured enzyme showed three main bands focusing at pH 5.0, 5.2, and 5.4. Kinetic properties (Vm and Km (atp) have been compared for the soluble and membrane bound ATPase in presence of various anions. Inhibitory effects of Quercetin and other flavonoids have been tested in order to get an insight on the interaction between ATPase and its natural inhibitor.


Biosynthesis of acid mucopolysaccharides by the surviving new born rat skin. I. - Kinetics of the biosynthesis at the polymer level.

1) The amounts of individual mucopolysaccharides in the new born rat skin have been estimated and their specific rates of labelling assessed in vitro. Total and percentage amounts of these polymers agree satisfactorily with previously published data. 2) Relative rates of labelling from [U14C]-glucose have been estimated by combining column chromatography separation and electrophoresis on cellulose acetate strips. Specific radioactivities have been measured either with respect to the total uronic acid content of the fractions or with respect to their quantitative staining with Alcian Blue. The two methods agreed satisfactorily. 3) Average biosynthetic rates almost identical for hyaluronic acid and the total sulfated mucopolysaccharides. However, within the latter fraction, heparin + heparan sulfate incorporate [U14C]-glucose about 4 to 5 times more rapidly than the chondroitin sulfates. This result could not be expected from previous data obtained in vivo and is discussed with reference to a possible heterogeneity of the cell material whence the various mucopolysaccharides originate. 4) In the presence of puromycin, labelling of the sulfated mucopolysaccharides stops almost immediately, indicating a stringent requirement for protein primers. Biosynthesis of hyaluronic acid is affected only after preincubation of tissue with puromycin (one hour) and subsequent incubation of two hours with [U14C]-glucose.


Heart contractile proteins.

That several proteins of the sarcomere differ from one muscle to the next is well documented, and it is becoming evident that homogeneous muscles, like the heart, are also species specific. 1) Clear-cut evidence is available concerning myosin, and, to date, several types of molecules have been described. a) The myosins of white skeletal, heart, and smooth muscle differ in the activity of their Ca2+ and K+ATPases, as also in the structure of their light subunits. b) The Ca2+ATPases of the various cardiac myosins have been shown to exhibit species differences and correlate with the speed of shortening of the muscle. 2) The structures of tropomyosin, some troponin components, and alpha actinin (but not actin) appear to be unlike in the different types of muscle. 3) These phylogenic modifications may be related to the changes characteristic of the particular muscles under pathological conditions, which are accompanied by substantial increase in protein synthesis.


Factors affecting risks of congenital malformations. I. Analysis of epidemiologic factors in congenital malformations. Report from the Collaborative Perinatal Project.

An analysis was made of over 30 demographic, biologic and medical variables in relation to risks of congenital malformations which occurred in the Collaborative Perinatal Project. The study population consisted of 46,689 single and multiple live births and fetal deaths about whom complete information was available on all study variables. Included in the analysis were 5 general malformation categories, 27 specific major, and 7 specific minor malformations. Several new associations were detected between epidemiologic factors and risks of specific malformations while other previously reported associations were confirmed by the present investigation. The analysis of general categories of malformations showed that multiple births had a higher frequency of major malformations than single births; whenever sex differences in incidence were noted, males, with few exceptions, had an excess of malformations over females; and maternal diabetes during pregnancy was associated with increased risk of major malformations in the fetus. Among specific findings of possible etiologic significance were that the risk for microcephaly was associated with infrequent prenatal visits and the presence of maternal hyperthyroidism; and unusually low weight gain and infrequent prenatal visits were associated with increased risk for lung hypoplasia. There was no significant effect of inbreeding of the fetus or mother on the risks of general or specific types of malformations. Anencephaly was more frequent among white than among Negro infants, whereas no difference in incidence was noted in spina bifida between the two racial groups. This finding points to an inconsistency in the hypothesis of common etiology for these malformations. Whites were also found to have significantly higher incidences over Negroes of pyloric stenosis, congenital dislocation of the hip, micrognathia, and pectus excavatum, while Negroes have higher incidences of metatarsus varus and inguinal hernia.


[Mechanism of hypothalamic influences on bile formation].

Acute experiments were conducted on male rats; it was revealed that electrical stimulation of the nuclei of the anterior hypothalamus led to reduction of choleresis and to a fall of the potassium content in the bile, increase of permeability of the connective tissue stroma of the liver and of cell membranes of hepatocytes. Stimulation of the posterior hypothalamic nuclei induced an increase in choleresis, of the concentration of potassium ions and cholates in the liver, and also of the cholinesterase activity in the serum and homogenates of the liver. Permeability of connective tissue structures of the liver and of the intercellular spaces of hepatocytes proved to fall. The influences of the hypothalamus on bile formation included a change in the functional activity of hepatocytes and of the production of a fluid fraction of the bile.


Biosynthesis of acid mucopolysaccharides by the surviving new born rat skin. II. - Specific labelling of individual monosaccharides from (U14C)-glucose. Metabolic origin of L-iduronic acid.

1)Individual monosaccharides (uronic acids and aminosugars) have been purified following specific hydrolysis of the mucopolysaccharides from new born rat skin (hyaluronic acid, heparin + heparan sulfate, chondroitin sulfate A, B and C), after incubation with [U14C]-glucose under various conditions and for varying incubation periods. The yields and the specificity of the methods used for hydrolysis are discussed. 2) Monosaccharides from hyaluronic acid and the sulfated mucopolysaccharide fraction are labelled at an approximately equal rate. In addition, high rates of labelling of glucosamine isolated from the sulfated fractions confirms the preferential labelling of (heparin + heparan sulfate) demonstrated with the sulfated polymers. 3) In all fractions, aminosugars are considerably less labelled than the corresponding uronic acids, which suggests the existence of endogeneous diluting precursor pools for the former monosaccharides. 4) No drift of radioactivity from D-glucuronate to L-iduronate could be demonstrated in sulfated mucopolysaccharides after inhibition of their biosynthesis by puromycin or diluting the labelled precursor pools. Hence it has not been possible to substantiate on the surviving tissue the C5 epimerization at the polymer level, as previously demonstrated by other authors with subcellular fractions of various origin.


Aplastic anemia: failure of patient leukocytes to stimulate allogeneic cells in mixed leukocyte culture.

One-way mixed leukocyte cultures were used to study the ability of cells from 53 patients with aplastic anemia and 65 of their HLA-identical siblings to stimulate and to respond to cells from unrelated individuals. The capacity of leukocytes from 28 of 53 patients to stimulate was diminished or absent, wheras their ability to respond remained comparable to that of cells from their HLA-identical siblings. Leukocytes from the group of patients with the lowest peripheral lymphocyte count were least stimulatory. The results indicate that in acquired aplastic anemia there exists a dissociation between stimulation and response in mixed culture.


[Functional analysis of the muscles of the anterolateral wall of the abdomen using electromyocartography].

The purpose of this study was to analyze the function of the superficial muscles of the anterolateral wall of the abdomen in dorsal decubitus by an original technique: electromyocartography. This technique attempts to monitor the individual or inter-subjective variations that complicate quantitative analysis of the overall electromyogram with integration of action potentials. It is shown that relative quantification of the areas explored with respect to the most active area considerably improves the consistency of the results. The most dependable electrode locations for the analysis of the abdominal muscles are determined. From a functional point of view: The rectus abdominis is active in flexion of the cranial portion of the trunk, either alone or in combination with right or left rotation of the trunk. Its activity is less, and predominates in the distal portion of the muscle, in flexion of the caudal portion of the trunk in combination with a 15 degree flexion of the hips. The obliquus internus abdominis, which can be explored only in a single area, is especially active in rotation. The obliquus externus abdominis plays a major role in stabilizing the pelvis when the lower limbs are involved in the movement of the trunk.


[Electromyocartography of the posterior and inferior wall of the abdomen during extension of the torso].

Analysis of the functions of the muscles of the inferior and posterior regions of the trunk was carried out by electromyocartography for the basic movements of extension of the trunk in ventral decubitus. For a given subject, the results varied little with time. By contrast, the results were substantially the same from subject to subject in the case of only one movement : extension of the caudal portion of the trunk combined with extension of the hips. A functional balance-sheet can be based only on this movement. The sacro-spinalis (without attempting to determine the respective roles of the various bundles) seems to be the only one involved in certain movements of extension of the trunk: Its action is at a maximum, highly variable, when the extension involves both the caudal and the cranial portions of the trunk; It is considerable in the extension of the caudal portion alone, and Moderate in the extension of the cranial portion alone.


The effect of in vivo chromium exposure on Na/K-and Mg-ATPase activity in several tissues of the rainbow trout (Salmo gairdneri).

The effect of in vivo chromium exposure on Na/K-and Mg-ATPase activity was studied in several tissues of the rainbow trout, Salmo gairdneri. Those tissues studied were: intestine, gill, liver, and kidney. Tissue chromium levels were determined for control rainbow trout and trout exposed to 2.5 mg Cr/1 (as chromate) for 48 hours. After exposure to chromium, inhibition of Na/K-ATPase activity, but not Mg ATPase activity, was observed. These results may partially explain the detrimental effects of hexavalent chromium on fish.


Preventing the birth of infants with Down's syndrome: a cost-benefit analysis.

The costs and economical benefits of providing routine prenatal diagnosis of Down's syndrome with termination of affected pregnancies in older pregnant women in the west of Scotland were examined. The potential economic benefits would be greater than the costs for women aged 40 and over, probably about equal to costs for those aged 35 and over, but less than costs if the service were extended to women under 35.


The effects of temperature and inhibitors on HCO3-stimulated swelling and ion uptake of monkey cerebral cortex.

In the presence of high concentrations of K+, additions of HCO3- as low as 0.35 mM caused a 23% increase in swelling, and concomitant increases in the chloride content of incubating monkey cerebrocortical slices. The uptake of chloride was accompanied by increased uptake of sodium and was highly temperature dependent, showing a marked activation at approximately 30 degrees C. A similar temperature activation was also found for a Mg2+-dependent, HCO3-stimulated ATPase activity in monkey cerebral cortex, consistent with a possible role for this enzyme in the K+ and HCO3-dependent swelling process and its associated ion movements. K+-dependent, HCO3-stimulated cerebrocortical tissue swelling with uptake of Na+ and Cl- was inhibited by acetazolamide indicating that carbonic anhydrase was also involved. The addition of ouabain also inhibited swelling and K+ and Cl- uptake at low concentrations, but led to increased swelling at higher concentrations ( greater than 10 mum). A similar biphasic effect on swelling was also seen following addition of ethacrynic acid.


The effects of EHDP on regenerating trabecular bone using in vivo microscopic, light and electron microscopic, and electron microprobe techniques.

Metallic chambers were implanted into the proximal tibiae of rabbits to permit microscopic examination of living bone in situ. The bone repair process secondary to the injury produced during installation of the chamber, was visualized. Six to 8 weeks after implantation, osteoid and/or bone could be seen. The effects of various doses of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on the repair and regeneration processes following chamber implantation were studied. Data from various techniques indicated that: (1) following low dose EHDP (0.25 mg/kg/day) chambers contained bone tissue morphologically and ultrastructurally indistinguishable from controls; and (2) with higher doses of EHDP (2.5 or 10 mg/kg/day) chamber contained spicules of normal osteoid, osteoblasts and osteocytes, but were devoid of osteoclasts. The effects of the various regimes of EHDP also were assessed on regenerated, trabecular bone contained within the tibia chambers three months after implantation of the chambers. Data from various methods of analysis supported the following conclusions: (1) the low dose of EHDP (0.25 mg/kg/day) had no toxic effects on the trabecular bone within the chambers but there appeared to be an increase in bone formation as compared to saline control; (2) higher doses of EHDP (2.5 or 10mg/kg/day) were not toxic to bone cells but thick osteoid seams formed on the trabecular bone within the chambers. No osteoclasts were found associated with the bone apparently due to the coverage of bone surfaces by osteoid seams; and (3) osteoid which accumulated after EHDP treatment of 2.5 mg/kg/day for 2 months remained uncalcified for as long as 2 months following withdrawal of EHDP administration. The results showed the value of tibial chamber for examining microscopically living bone in situ and demonstrated the inhibitory effect of EHDP on mineralization of newly formed osteoid and a lack of effect on bone cells.


Subcellular and functional effects of quinidine, procaine amide, and lidocaine on rat myocardium.

Different antiarrhythmic agents such as quinidine, procaine amide, and lodocaine at 1 mM concentrations were found to depress the ability of an isolated perfused rat heart to generate contractile force. Quinidine, but not procaine amide or lidocaine, decreased calcium uptake by both mitochondrial and microsomal fractions at different concentrations of calcium. The mitochondrial phosphorylation rate, respiratory control index, and state 3 oxygen consumption, but not ADP:O ratio and state 4 oxygen consumption, were depressed by only quinidine. None of these agents had any effect on myofibrillar Mg2+-ATPase or Ca2+-stimulated ATPase activities. On the other hand, sarcolemmal Mg2+-ATPase and Ca2+-ATPase activities, but not Na+-K+-ATPase activity, were increased by all these drugs. The sarcolemmal adenylate cyclase (EC 4.6.1.1) activity was decreased by quinidine only. These results suggest some similarities and differences in the sites of action of quinidine, procaine amide, and lidocaine within the myocardium.


Excitation-contraction coupling in heart. XIX. Effect of hypoxia on calcium transport by subcellular particles in the isolated perfused rat heart.

To examine the role of changes in calcium transport by subcellular particles in the pathogenesis of contractile failure due to oxygen lack, both mitochondrial and microsomal fractions were obtained from the isolated hypoxic rat hearts and their calcium binding and uptake abilities were determined by the Millipore filtration technique. The contractile force decreased by about 40, 60 and 70% of the control within 5, 10 and 30 min respectively, of perfusing the heart with hypoxic medium containing glucose. In hearts perfused for 10 min with hypoxic medium containing glucose, calcium binding and uptake by the microsomal fraction decreased significantly. However, mitochondrial calcium binding, but not uptake, decreased significantly on perfusing the hearts with hypoxic medium containing glucose for 20 to 30 min when the microsomal calcium transport was markedly depressed. Reduction in contractile force, calcium binding and uptake by the microsomal fraction as well as calcium binding by mitochondria of hearts made hypoxic for 30 min recovered towards normal upon reperfusion with control medium for 15 min. On the other hand, omitting glucose from the hypoxic medium significantly decreased calcium binding by mitochondrial and microsomal fractions within 10 min of perfusion in comparison to the control and accelerated the effects of hypoxia upon contractile force and microsomal calcium uptake. In contrast to the hypoxic hearts, the mitochondrial calcium uptake decreased significantly and the magnitude of depression in the microsomal calcium binding was appreciably greater in hearts made to fail to a comparable degree upon perfusion with substrate-free medium. The observed defects in calcium transporting properties of microsomal and mitochondrial membranes appear secondary to the contactile failure in hypoxic hearts.


The influence of splenectomy on cellular immunologic parameters in Hodgkin's disease.

Cellular immunity was evaluated in 15 untreated patients with Hodgkin's disease before and about 10 days after splenectomy. Skin test-reactivity was not affected by the operation. The number of lymphocytes was moderately increased in patients with pathologic stage I and II disease. The relative proportion of E-binding lymphocytes in the peripheral blood diminished significantly (p = .001) in patients with splenic weights of 240 g and more, whereas the PHA-stimulated thymidine incorporation increased significantly (p = .015) and the proportion of EAC-binding lymphocytes increased significantly (p = .023). The PHA-stimulation of peripheral lymphocytes in patients with pathologic stage I and II disease was at the same level before and after operation, but increased significantly (less than 0.02) in the more disseminated forms. The stimulation of the lymphocytes in vitro by a cocktail of antigens, and by allogeneic cells (MLC) remained unchanged. Although the number of cases studied is rather small, it is concluded that about 10 days after, splenectomy has no demonstrable untoward effect on the cellular immunologic potency.


"Endometrial" adenocarcinoma of the prostate: a distinctive tumor of probable prostatic duct origin.

A so-called "endometrial" adenocarcinoma of the prostate has been studied by light and electron microscopy, and by histochemical techniques. The previously proposed utricular origin and estrogen dependence of such tumors is questioned. Strong acid phosphatase staining, and the ultrastructural demonstration of multivacuolated, lipid, and lysosome-containing tumor cells, suggest a prostatic ductal origin for this type of carcinoma despite the histologic similarity to carcinoma of the endometrium.


Hyperprolactinemia and steroid metabolism by rat mammary adenocarcinomas.

The metabolism of both testosterone and dehydroepiandrosterone by 10 adenocarcinomas induced and grown in the presence of high prolactin (plasma prolactin greater than 220 ng/ml) was compared with the metabolism of 10 adenocarcinomas induced and grown in the presence of normal levels (plasma prolactin less than 60 ng/ml). The tumors associated with high prolactin significantly metabolized more testosterone to both 5alpha-dihydrotestosterone and 5alpha-androstanediol. The metabolism of dehydroepiandrosterone was similar in both groups of tumors. It is concluded that prolactin may differentially influence the metabolism of C19 steroids by rat mammary adenocarcinomas.


Anionic polysaccharide production and tyrosinase activation in cultured human melanoma cells.

A human melanoma cell line established in our laboratory was characterized in terms of tyrosinase activity and anionic polysaccharide production. Tyrosinase levels were diluted during the growth phase and increased after the cell culture became confluent. The anionic polysaccharides produced included hyaluronic acid, heparitin sulfate, and a high-molecular-weight condroitin 4-sulfate. In contrast, a primary culture of human melanocytes derived from embryonic iris produced much greater amounts of hyaluronic acid, about 30-fold less heparitin sulfate, and a mixture of chondroitin 4-sulfate and dermatan sulfate. Saccharides secreted into the culture medium were generally identical to those remaining cell associated except for the melanoma heparitin sulfate, wherein the latter fraction appeared to be of lower molecular weight.


Effects of 2-amino-1,3,4-thiadiazole on ribonucleotide pools of leukemia L1210 cells.

The effects of 2-amino-1,3,4-thiadiazole [aminothiadiazole (NSC 4728)] on purine and pyrimidine ribonucleotide pools of L1210 ascites cells in vivo are presented and discussed as they relate to the site of action. Within 1 hr after administration of the drug, the levels of guanosine triphosphate, guanosine diphosphate, adenosine triphosphate, and adenosine diphosphate were reduced, whereas those of inosine monophosphate (IMP) and uridine triphosphate were increased. The most pronounced effects were the lowering of guanine ribonucleotide pools and the elevation of IMP. Aminothiadiazole produced a marked inhibition (approximately 95%) of the incorporation of [8-14C]inosine into guanine nucleotides, whereas only a slight inhibition (approximately 20%) of incorporation into adenine nucleotides was observed. These results suggest that the thiadiazole (or a metabolite thereof) inhibits the conversion of IMP to guanosine monophosphate; this conclusion is reinforced by the observation that mycophenolic acid, a known inhibitor of this conversion, produced effects on ribonucleotide pools similar to those produced by aminothiadiazole. Aminothiadiazole did not inhibit IMP dehydrogenase isolated from L1210 cells. The effects of the thiadiazole on nucleotide pools were prevented by simultaneous administration of nicotinamide. Since nicotinamide is known to prevent or reverse the antileukemic activity of aminothiadiazole, it is probable that the inhibition of synthesis of guanosine monophosphate is related to the antileukemic action of this agent.


Effect of a spermatogonial chalone on the growing rat testis.

Immature rats were used in an experiment to test the possible influence of a spermatogonial chalone on the expanding spermatogonial population in their developing testes. An extract from adult rat testes was injected intraperitoneally into 33-day-old rats and control animals were injected with an equal amount of saline. Two groups of normal adult rats similarly injected with the testicular extract and saline solutions served as additional controls. Following these injections, all animals were administered a dose of 3H-thymidine 10 hr before sacrifice. An analysis of the labeling indices of the various types of spermatogonia revealed that in young rats injected with testicular extract the percentage of labeled type A spermatogonia was significantly lower than in control animals. In contrast, the labeling indices of Intermediate and type B spermatogonia were similar in the two groups of young rats. In the two groups of adult animals, there was no difference  in the labeling indices of type A or of other types of spermatogonia. These data indicated that the saline extract of adult testes contained a substance, a spermatogonial chalone, inhibiting specifically the proliferation of some type A spermatogonia. The results also support the concept that a spermatogonial chalone may intervene, through its action on the spermatogonial stem cell population, to arrest the growth of the seminiferous tubules as the animal reaches maturity.