[Effects of capsules of Staphylococcus aureus on the rosette formation with B-lymphocytes and macrophages (author's transl)]. After extraction with guanidium chloride nonencapsulated Staphylococcus aureus (S-Gu) and yeast cells (Hefe-Gu) reduced the hemolytic complement activity of normal human and guinea pig sera much more (fig 1) than encapsulated S. aureus (KS-Gu). Following incubation in the fresh sera S-Gu, Hefe-Gu and guanidinium chloride-extracted S. epidermidis, contrary to KS-Gu, had activated C3 on their surface. Therefore, they formed rosettes with human B-lymphocytes (fig. 2,3,4) and peritoneal macrophages from guinea pigs. The adherence-reactions were less frequent. if the pre-incubation was conducted in the heat-inactivated (30 min, 56 degrees C) sera (table 1,2). After pre-incubation in the absence of serum only the protein A-positive S-Gu formed rosettes with B-lymphocytes.


Root formation in ectopically transplanted teeth of the frog, Rana pipiens I. Tooth morphogenesis. In order to determine the intrinsic (genetic) and extrinsic (functional) parts of the naturally ankylosed tooth, a qualitative study of the development and fate of tooth buds transplanted individually or within the premaxilla was carried out. These teeth were transplanted as autografts during crown formation. They were placed in either the anterior chamber of the eye or in a dorsal subcutaneous site. Most of the 163 transplants survived and were examined at intervals from 0 to 180 days by gross, histologic and microradiographic methods. Tooth buds transplanted with or without the premaxilla were capable of growth to normal size and shape. Lack of underlying bone with which to ankylose and lack of normal oral environment and function did not prevent formation of a normal-sized root area. The root area was composed of dentin and covered by a solid, undisrupted Hertwig's epithelial root sheath which appeared to mold the root. Calcified tissue formed on the outside surface of dentin only when the root sheath was accidentally torn during transplantation.


Ultrastructural and functional aspects of frog heart lesions after isoproterenol. The purpose of the present study was to explore the possible correlation between the ultrastructural changes and the functional changes induced by isoproterenol (IPR) in the myocardium of the frog. The study was performed on winter frogs (R. pipiens), The experimental animals wend then given 2 daily doses of IPR (200 mg/kg b,w.). Twenty-four hours after the second IPR dose, specimens were taken from the heart ventricle and subjected to electron microscopical examination and to analysis of the isometric force decay in response to anoxia produced by sodium cyanide. Specimens were taken from macroscopically non-damaged portions of the ventricle as well as from aneurysms. Control animals were kept at + 8 degrees C and + 25 degrees C and injected with saline. In all IPR-injected animals the specimens from macroscopically non-damaged parts of the myocardium showed ultrastructural changes characterized by a relative increase in mitochondrial mass and a pronounced reduction of glycogen. Specimens from aneurysms showed similar changes but in some fibres signs of more severe injury were observed such as fragmentation of the cristae of the mitochondria and disintegration of myofibrils. The functional analyses showed that the isometric force decay of the heart muscle strips induced by the respiratory block by cyanide was much greater in specimens from IPR-treated animals than in those from control frogs. The augmented force decay was found in both strips from macroscopically normal parts of the myocardium and in those from aneurysms although it was somewhat greater and more rapid in the latter. The observed, minor functional difference between macroscopically non-damaged portions of the myocardium and aneurysms is remarkable with respect to the different preservation of myofilaments in these regions. This similarity in functional decline could possibly be due to the observed homogenous reduction of glycogen in the IPR-exposed myocardium since glycogen was the only source of ATP under the experimental conditions of current interest.


First pass conjugation and enterohepatic recycling of oxazepam in dogs; intravenous tolerance of oxazepam in propylene glycol. Oxazepam dissolved in propylene glycol was administered intravenously to dogs. There were no cardiac or general adverse effects. Hemolysis and thrombophlebitis were observed after rapid infusion (5.6 ml in 1 minute), and were shown to be due to the properties of the vehicle. Comparison of plasma concentration time curves after oral and intravenous administration indicated a bioavailability of 70 +/- 15 S.D. %. The decreased availability after oral dose was considered to be due to first pass elimination as the urinary recovery of metabolites was the same after the two routes of administration. This also indicates complete absorption. In a dog with a chronic biliary fistula 15 mg of oxazepam was given intravenously on two occasions. When normal bile flow into the gut was permitted the disposition of oxazepam was similar to that in normal dogs. When bile was withdrawn the elimination of oxazepam was more rapid with an increase of apparent plasma clearance. In this case 32% of the dose was excreted as conjugates in the bile within 3 hours after administration. In the normal dogs 2-20% of the dose given was recovered in the faeces as the parent compound and practically no conjugates were found. These findings indicate enteral hydrolysis of the conjugates, and a marked enterohepatic recycling or oxazepam.


Pharmacokinetics of oxazepam in healthy volunteers. The pharmacokinetics of oxazepam was studied in healthy volunteers. When oral doses of 15 mg were given to eight subjects on two occasions 2.5 years apart the individual areas under the plasma concentration time curves did not differ significantly. Plasma clearance ranged between 0.050 and 0.171 x kg-1 x h-1 and half-lives from 5.9 to 25 hours. The urinary recovery of oxazepam conjugates was 67 +/- 15 S.D.% of the dose given and the total recovery including faecal oxazepam was 70 +/- 15 S.D. %. On multiple dosing (5 mg t.i.d.) stable steady-state concentrations were established. There was a tendency for slightly lower steady-state concentrations than predicted from single oral doses. During steady-state 86 +/- 17 S.D. % of the dose was recovered in the urine over a 24 hour period.


Oxazepam disposition in uremic patients. The pharmacokinetics of oxazepam was investigated in 13 uremic patients. The apparent terminal half-life of oxazepam in plasma was 24-91 hours compared to 5.9-25 hours reported elsewhere for healthy volunteers. The plasma concentrations showed secondary peaks about 24 hours after the dose and this probably gave rise to the increase in half-life. Plasma clearance of oxazepam appeared to be normal. The conjugated metabolites accumulated to concentrations 5-50 times those of the parent compound and could still be detected 5 days after a single oral dose (0.2 mg/kg). Renal clearance of conjugated oxazepam was significantly correlated to creatinine clearance. The urinary recovery over 5 days was 18-57%. The faecal recovery of 3 days was 0.1-19%. In some patients up to 49% of oxazepam in faeces was in the conjugated form. It is concluded that enterohepatic recycling of oxazepam might occur in uremic patients but is not of great quantitative importance. During multiple dosing the accumulation of conjugates was even more pronounced, with plasma concentrations amounting to 14-61 times those of oxazepam. Steady-state plasma concentrations of oxazepam was similar to those obtained in normal subjects.


Multiple oral doses of diazepam, oxazepam and phenobarbital to dogs--behavioural effects and correlation with antipyrine half-life. The effects of prolonged treatment with phenobarbital, diazepam, and oxazepam on behaviour and on the plasma half-life of antipyrine have been studied in the dog. In this species the biotransformation of diazepam and oxazepam is known to be very similar to man. After equipotent doses of phenobarbital (25 mg/kg) and diazepam (35 mg/kg), antipyrine half-life was found to decrease 80 and 40%, respectively, while after treatment with oxazepam (150 mg/kg) there was an increase of 20%. The behavioural effects declined in the dogs during the course of treatment with diazepam but were rather constant during treatment with oxazepam.


Effect of long-term vitamin D2 treatment on bone morphometry and biochemical values in anticonvulsant osteomalacia. Quantitative morphometric analyses of iliac crest biopsies from 20 epileptic patients receiving chronic anticonvulsant therapy have been performed before and after 4-8 months of vitamin D2 treatment with 9 000 U per day. Biochemical quantities, including serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH), were measured. The anticonvulsant osteomalacia found in the initial bone biopsies was characterized by an increased amount of ummineralized bone, an increased bone resorption and, contrary to vitamin D deficiency, an increased bone mineralization and bone formation. Bone resorption and bone formation were probably equally increased since the amount of cancellous bone was normal. Except for a slight increase in osteoidcovered surfaces and osteoclastic resorption surfaces, the bone changes were normalized after vitamin D2 treatment, leading to a mean serum level of 25-HCC 2.4 times above normal. Serum iPTH was normal before and unchanged during D2 therapy. The urinary calcium excretion remained decreased. The investigation characterizes anticonvulsant osteomalacia as a specific bone disease different from that of vitamin D deects of vitamin D metabolites on receptor cells.


Retinitis pigmentosa: accelerated course of visual loss secondary to exogenous thyroid administration. A 30 year old white female with known retinitis pigmentosa of autosomal dominant transmission was placed on thyroid medication for weight control purposes for nearly one year. The unusually rapid progression of visual field changes and the increased severity of night vision problems are documented by serial functional studies.


Left ventricular performance and graft patency after coronary artery-saphenous vein bypass surgery: early and late follow-up. Left ventircular performance and graft patency were studied postoperatively at 2 weeks in 19 patients, and at 9 months in 15 patients. At early follow-up, left ventricular ejection fraction and mean rate of circumferential shortening were unchanged for the group as a whole, but were slightly improved in patients who had had a moderately abnormal preoperative ejection fraction of 0.30 to 0.60. At late follow-up, 10 of 14 patients had occluded at least one graft or the proximal segment of the grafted coronary artery and had an associated decrease in ventricular function. The risk of graft occlusion was greater if the preoperative ejection fraction was decreased; seven of 10 patients with a preoperative EF of less than 0.60 suffered one or more graft occlusions, but only three of 16 patients with a preoperative EF greater than 0.60 had a postoperative graft occlusion (p is less than 0.05). The results suggest that bypass graft surgery is not generally indicated as a measure to improve ventricular function in patients with ischemic heart disease.


Effects of amyl nitrite on phasic aortocoronary bypass graft blood velocity in man. With the use of a Doppler flowmeter catheter, phasic instantaneous aortocoronary saphenous vein bypass graft blood velocity was continuously measured during the inhalation of amyl nitrite in 20 closed-chest conscious subjects. Administration of amyl nitrite augmented peak diastolic and systolic graft blood velocity within 10 seconds and maximal blood velocities were recorded between 8 and 60 seconds after inhalation. Control mean (+/- 1 S.D.) bypass graft blood velocity was 25 +/- 10 cm. per second and after amyl nitrite 46 +/- 14 cm. per second, resulting in an average 84 per cent rise of blood velocity. It is concluded that amyl nitrite increases aortocoronary bypass graft blood velocity, suggesting a possible enhancement of blood flow to the distal native circulation in patients so operated upon.


Sodium nitroprusside as a coronary vasodilator in man. I. Effect of intracoronary sodium nitroprusside on coronary arteries, angina pectoris, and coronary blood flow. The effect of the intra-arterial injection of 5 to 10 microng of sodium nitroprusside on the caliber of normal and diseased coronary arteries was evaluated in 21 patients during diagnostic cardiac catheterization. In addition, the effect of intra-graft injection of 5 microng of the same agent on the blood flow in aorta-right coronary artery saphenous vein bypass grafts was also evaluated intra-operatively in two patients. The compound induced an increase in the caliber of both normal and stenosed coronary arteries as well as an increase of flow in the grafts. Consistent with measurements of coronary flow response to sodium nitroprusside, angina pectoris which developed in four patients during cardiac catheterization was immediately relieved and the ischemic ST-segment depression significantly reversed after injection of 5 to 10 microng of the drug into the left main coronary artery. Within the dose range used, the drug caused no significant effect on systemic blood pressure or apparently deleterious electrophysiologic changes. No side effects were observed. We conclude that the primary direct action of sodium nitroprusside in the human coronary artery is vasodilatory.


Asymptomatic coronary artery disease and coronary bypass surgery. The actuarial survival curves of "medically treated" patients whose arteriographic studies demonstrated coronary arterial lesions of various degrees-- now used widt applicable to the asymptomatic patient. No information is available regarding the course or prognosis of the asymptomatic patient with demonstrated lesions in the coronary arteries. For the reasons explained one can propose a hypothesis that the overall prognosis of this type of patient is better than average, probably better than that shown in the best data collected on symptomatic patients. The prophylactic value of aortocoronary bypass operations in preventing myocardial infarction and death has not been established. One can therefore question the justification for the wide case-finding effort of subjecting asymptomatic persons to coronary arteriography, even in light of the low risk of this procedure, unless unusual findings suggest an especially poor prognosis (one example might be past myocardial infarction in a very young patient). Although there are exceptional instances when prophylactic surgery is indicated for asymptomatic patients, further investigation of this subject is needed before the procedure becomes generally accepted.


Fine structure of the secretory and nonsecretory ameloblasts in the frog. I. Fine structure of the secretory ameloblasts. Amelogenesis in the tooth germs of the frog Rana pipiens was examined by electron microscopy at different stages of tooth development. Cellular changes in secretory ameloblasts during this process showed many basic similarities to those in mammalian amelogenesis. Amelogenesis can be divided into three stages based on histological criteria such as thickness of enamel and the relative position of the tooth germ within the continuous succession of teeth. These stages are early, transitional and late. The fine structure of the enamel-secreting cells reflects the functional role of these ameloblasts as primarily secretory in the early stage, possibly transporting in the late stage and reorganizing between the two functions in the transitional stage. In early amelogenesis the cell exhibits well-developed granular endoplasmic reticulum, Golgi complex, microtubules, dense granules, smooth and coated vesicles, lysosome-like bodies in supranuclear and distal portions of the cell and mitochondria initially concentrated in the basal part of the cell. Numerous autophagic vacuoles are observed concomitant with the loss of some cell organelles at the transitional stage. During late amelogenesis the ameloblasts exhibit numerous vesicles, granules, convoluted cell membranes, junctional complexes and widely distributed mitochondria. Toward the end of amelogenesis, cells become oriented parallel to the enamel surface and the number of organelles is reduced. Amelogenesis in the frog is an extracellular process and mineralization seems to occur simultaneously with matrix formation.


Musculoskeletal changes immediately following acupuncture. Electrically augmented acupuncture stimulation was applied to two volunteer subjects who presented with a variety of symptoms. The subjects were given osteopathic musculoskeletal examinations immediately before and after acupuncture stimulation. Prior to stimulation, both subjects were found to have musculoskeletal dysfunctions affecting a number of body regions. After acupuncture had been administered at loci selected with reference to traditional methodology, some but not all of the dysfunctions were found to be altered in the direction of normalization. Those which had changed were the ones judged most likely to be related to the symptoms of the subjects.


Electro-acupuncture treatment in psychiatry. In the course of treatment by Dr. H.L. Wen's technique of acupuncture for the withdrawal symptoms of various drugs, it was noted that there was a relief of neurotic symptoms, tension, restlessness and depression. Therefore, this treatment was used on neurotic patients. Forty patients ranging in age from 22 to 61 years were treated. Case reports are given on four patients. The degree of relief from neurotic symptoms was most marked in symptoms of restlessness, tension, mental and physical fatigue, loss of appetite and irritability, in that order. Obsessional symptoms showed a poor response. It is concluded that electro-acupuncture is useful in the treatment of neurotic symptoms, that it is cheaper and safer than other methods of treatment in use at this time, and that it is a useful adjunct in the treatment of psychoneurosis.


Lightning injury: management of a case with ten-day survival. A boy, injured by lightning, had cardiopulmonary arrest. Following resuscitation and during the course of hospitalization, he developed further cardiac arrhythmia, cerebral edema, generalized seizures, and upper gastrointestinal bleeding. Despite efforts to combat these complications, the patient's condition deteriorated, and he died on the tenth day of hospitalization. The pathologic findings are described and the treatment discussed.


Risk factors in chronic obstructive pulmonary disease (COPD). In a genetic-epidemiologic study of chronic obstructive pulmonary disease (COPD) observations adjusted for age, sex, race, and smoking indicate certain factors to be associated with increased pulmonary function aberrancy, and suggest that they are risk factors for COPD. These presumptive "risk factors" include not only cigarette smoking, but also alpha1-antitrypsin (Pi system) variation, one or more other familial components, low socioeconomic status (SES), and, in whites, ABO blood type (either absence of "B" or presence of "A").


Pulmonary infiltrates and fever in patients with hematologic malignancy: assessment of transbronchial biopsy. Pulmonary infiltrates associated with fever are frequently encountered in patients with acute leukemia or lymphoma; In this prospective series, we analyze 47 such episodes in 43 patients. Overall mortality was 45 per cent in patients with infiltrates and somewhat higher when they also had neutropenia (55 per cent) or acute leukemia (67 per cent). Pulmonary infiltrates could be categorized into three roentgenographic patterns: local consolidation (55 per cent); cavitary disease (13 per cent) and diffuse interstitial disease (32 percent). The exact etiology of the infiltrates could not be predicted by roentgenographic study. Microbiologic or histopathologic diagnosis was established during life in 57 per cent of the patients, with infection most commonly encountered. Twenty-one patients underwent lung biopsy procedures. Biopsy specimens were frequently diagnostic (n = 17) and often dictated therapeutic changes (n = 12). Transbronchial lung biopsy via the fiberoptic bronchoscope was utilized in 14 patients during the latter part of this study; diagnoses were obtained in nine patients. Morbidity was minimal with this procedure, and the need for thoracotomy was diminished when it was available.


Coronary artery aneurysms: study of the etiology, clinical course and effect on left ventricular function and prognosis. Coronary artery aneurysms were found in 16 men between 37 and 62 years of age, mean 51 years. Aneurysms were of two types: saccular and fusiform. They involved the right coronary artery in 13 (87 per cent), the circumflex artery in eight (50 per cent) and the left anterior descending artery in five (31 per cent). In some patients, more than one vessel was involved. Twelve patients presented with angina pectoris, three with congestive heart failure and one with both. Five were in functional class II, eight were in class III and three were in class IV at the beginning of the study. The electrocardiogram showed evidence of previous myocardial infarction in four patients; four patients had left ventricular hypertrophy, one had left axis deviation, one had left  bundle branch block, one had right bundle branch block, two had first degree atrioventricular block and seven had abnormalities in the S-T segment and T wave. Obstructive coronary disease was present in all; the obstruction score was from 1 to 4 in three patients, from 5 to 9 in four patients and from 10 to 14 in the remaining nine. Similar aneurysms were found in the pulmonary artery of one patient and in the abdominal aorta of three patients; in seven of 14 patients with adequate venous angiograms, varicosities of the coronary venous tree were observed. Left ventricular dysfunction and angina pectoris were noted in patients with significant obstructive coronary disease (greater than 70 per cent) and also in patients without obstruction but with coronary aneurysms. Ten patients were treated surgically; nine underwent aortocoronary bypass and one mitral valve replacement. Criteria for bypass was the presence of obstructive disease and medically unresponsive angina pectoris. All but one surgically treated patient showed improvement. The functional class in medically treated patients was unchanged. Fourteen patients were still alive at the completion of the study. The findings of this study suggest that angina pectoris and left ventricular dysfunction can occur with coronary artery aneurysm without coronary artery obstructions. Coronary aneurysms may be a subset of atherosclerosis, and this process may involve other vascular territories. The prognosis in those patients appears to be no worse than in patients with obstructive coronary disease and no aneurysms.


Surgery for duodenal ulcer. A study relating indications to the results of surgery. The present study correlates the indications for operation in 215 patients with duodenal ulcer disease with the results of operative management. The majority of patients had conservative surgery utilizing truncal vagotomy and pyloroplasty or gastrojejunostomy. None of the 194 patients operated on electively died and four patients died after emergency operations, for an overall operative mortality in the entire series of 1.8 per cent. The incidence of recurrent ulcer symptoms in all patients was 10 per cent. We could demonstrate only a modest correlation between indications for operation and long-term results of conservative surgical management; the indication for surgery, whether that of chronic (intractability, stenosis) or more acute (hemorrhage, perforation) ulcer disease is only moderately reliable as a predictor of long-term results. In this series of patients, those with obstructing duodenal ulcers (pyloric stenosis) had the best long-term results after conservative surgical management.


Multidisciplinary treatment for childhood sarcoma. Surgical extirpation of the primary tumor has traditionally been utilized as initial treatment for sarcomas in children. The present report, however, demonstrates that sarcomas are optimally treated by means of a coordianted multidisciplinary approach. The latter offers the potential for achieving improved survival and preservation of organs and limbs, particularly for structures of the head and neck, for extremities, and in the genitourinary system.


The treatment of patients with recurrent ventricular fibrillation. During the four year period from 1972 to 1975, eleven patients, eight with recurrent and three with first attacks of ventricular fibrillation, underwent aortocoronary bypass graft and/or resection of ventricular aneurysm. All patients had old myocardial infarction from seven weeks to six years. Left ventricular angiography demonstrated discrete aneurysm of the anterior wall of the left ventricle in nine of the patients and akinesis or hypokinesis of the anterior and posterior wall of the left ventricle in the remaining two. Coronary angiography was carried out in ten patients and revealed significant disease of the left anterior descending and right coronary arteries in ten and nine patients, respectively. There was no operative mortality, and there were two late deaths. Eight patients have improved significantly and have had no further sign of ventricular irritability. The present study indicates that aortocoronary bypass graft and/or resection of ventricular aneurysm is an effective method of therapy for patients with repeacted ventricular fibrillation who have ventricular aneurysm and ischemic heart disease.


Preoperative intra-aortic balloon assist in high risk revascularization patients. Sixty-five high risk myocardial revascularization patients had preoperative IABP with two operative deaths. Only six patients needed rapid institution of cardiopulmonary bypass after anesthesia induction despite marked blood pressure drop in half the patients. There were only two instances of postpump power failure. Preoperative IABP is a valid method of limiting morbidity associated with coronary surgery in high risk patients.


The incidence and clinical significance of antibodies to extractable nuclear antigens. Sera from 378 patients were assayed for antibodies to extractable nuclear antigens (ENA), ribonucleoprotein (RNP) and nonnucleoprotein (Sm). Anti-ENA antibodies were not found in control subjects, patients with rheumatic diseases and negative fluorescent antinuclear antibodies (FANA), or in patients with rheumatoid arthritis, dermatomyositis, drug-induced lupus, idiopathic thrombocytopenic purpura (ITP), or hemolytic anemia with positive FANA. Anti-Sm antibodies were found in 32 per cent of patients with systemic lupus erythematosus (SLE) and were not found in any other condition. There were no significant clinical or serological differences between patients with and without anti-Sm antibodies. Anti-RNP antibodies occurred in 15 per cent of SLE patients, 9 per cent of scleroderma patients, and in 100 per cent of patients with mixed connective tissue disease. SLE patients with anti-RNP antibodies had a significantly lower anti-DNA antibody titer and a significantly lower incidence of nephritis and impaired renal function. Anti-Sm and anti-RNP titers did not vary with changes in clinical status. Awareness of the presence of anti-Sm and anti-RNP antibodies is diagnostically useful. Anti-RNP antibodies have a prognostic value as well.


[Seesaw nystagmus: symptom of a biochemical disorder (author's transl)]. A case of the rare seesaw nystagmus is presented and compared as for identity with an another case, reported by this author earlier. Some new finds were made, completing the first observation, published 1974 [27]. Both the cases of the seesaw nystagmus were found to have the same biochemical disorders: the cystathioninuria and the hypopyridoxalphosphatemie.


The role of lactic acid in neovascularizations. In this study the aqueous lactate concentration was determined. There was a significant increase of the aqueous lactate content in cases of rubeosis iridis and in cases of large intraocular malignant melanoma where a rubeosis iridis was present in 22%. These data seem to confirm the importance of the increased lactate concentration in neovascularizations.


[Results of objective accommodation determination in eyes with alternating functional central scotoma (alternating strabismus) (author's transl)]. Objective determination of monocular accommodation in young eyes revealed a different behaviour in strabismus alternans from that in normal binocular vision. This manifested itself by strongly differing individual responses, less correct values in physiological and unphysiological accommodation tests, and different reactions on hindering clear vision that cannot be compensated by refraction changes. The possibility of central scotoma, persisting during fixation and varying in density, occurring in alternating strabismus, is discussed.


[Tonographic and tonometric aqueous humor outflow tests after trabeculotomy (author's transl)]. In 10 eyes which trabeculotomy was performed because of primary open angle glaucoma preoperatively, 1 to 3 months and 12 months postoperatively the diurnal curves and tonographic results were compared. The i.o. pressure was reduced in all eyes. The ocular rigidity was decreased from 0.0206 +/- 0.0019 (s.d.) preoperatively to 0.0164 +/- 0.0015 after 1 to 3 months and to 0.0168 +/- 0.0017 after 12 months. Regarding the individual change of ocular rigidity, the outflow facility was improved on an average of from 0.13 +/- 0.02 preoperatively to 0.37 +/- 0.10 or 0.20 +/- 0.03 units postoperatively. This means a reduction of the resistance to aqueous outflow from 10.62 +/- 1.89 to 3.88 +/- 0.57 or 5.77 +/- 0.77 units. The differences are statistically significant. If the changings of ocular rigidity are not regarded there is no significant improvement of the conditions of aqueous humor outflow.


[Experiences gained with a combined ketamin anaesthesia for eye-surgery on cats (author's transl)]. A combined anaesthesia with ketamine, urethane und propionylpromazine was performed on 30 cats for lengthy eye-surgery operations. This schedule of anaesthesia proved to be most advantageous because of the promt onset and the sufficient degree of anaesthesia, which could be maintained for hours without complications. Open manometric tonometry showed no raised intraocular pressure during the anaesthesia with a mean value of 27.6 mm Hg, which is within the normal range of IOP for cats.


What happens when hospitalized patients see their own records. The effect of giving hospitalized medical patients access to their problem-oriented hospital records was investigated. Twenty-five subjects were given free access to their records while 25 other subjects served as controls. Few of the open record group actively sought and studied their records; most elected to see them only as part of routine ward rounds; and one objected to seeing the record at all. Taking the experimental group as a whole, there was no measurable effect of seeing the record on the subjects' ability to list their diagnoses or medications, their self-assessment of depression, anxiety or contentment, or their attitudes toward selected components of the health care system. On the other hand, in individual instances access to the hospital record seemed to facilitate communication and provide an opportunity for hospital inpatients to monitor objectively their hospital course.


Sickle cell trait and hematuria associated with von Willebrand syndromes. A von Willebrand syndrome was present in four patients with sickle cell trait and hematuria. The first two patients had severe anemia and active bleeding and received cryoprecipitate, with prompt cessation of hemorrhage. All of the patients had repetitive laboratory and clinical features; that is, reduced, but detectable, factor VIII-related antigen, heterogeneity of, and incongruities within, the coagulation studies performed by consistently defective platelet aggregation to ristocetin correctable only with normal plasma. Bleeding outside the genitourinary tract never was observed. Because of the focal nature of the hemorrhage, the hematuria may not have been perceived as part of a general hemorrhagic disorder and the diagnosis not pursued. These observations suggest that when sickle cell trait and hematuria occur together, a von Willebrand syndrome should be a major diagnostic consideration that ultimately may point toward a rational, effective, easily administered, and clinicially acceptable form of treatment with cryoprecipitate.


Ototoxic interactions of ethacrynic acid and streptomycin. Various aminoglycoside antibiotics and potent diuretics are known to depress cochlear and vestibular function. Several clinical and research studies suggest that the drugs administered together produce enhanced ototoxicity. The present series of experiments determines the depressive effects of ethacrynic acid and streptomycin, alone or in combination, upon the vestibular system of the cat. The changes in function, when quantified, indicate an addition, rather than a potentiation of toxicity, and suggest different sites of action.


Effect of CO2 on the perilymphatic oxygen tension in cats. A microelectrode with a tip of 100micron permitting recording of the oxygen tension in the perilymphatic space according to the polarographic principle and having a minimal drift of 1-25% per hour has been developed. The effects of apnea, hypo- and hyperventilation as well as those of inhalation of pure oxygen, and CO2 upon the perilymphatic PO2 have been measured by placing the electrode in the perilymph through the fenestrated stapedial footplate of 87 adult cats. The correlation between the arterial PO2 and the perilymphatic PO2 is so close that even hypo- or hyperventilation in presence of air does influence the oxygen content of the perilymphatic space. In view of the effect of the smallest accumulation of alveolar CO2, particular attention has to be paid to the system used for respiration of the experimental animal, when determining the action of drugs or inhaled gas mixtures on the oxygenation of the inner ear fluids. The measurement of the perilymphatic oxygen tension also indicates that the rate of blood flow cannot be used to deduct with accuracy the actual degree of oxygenation of the inner ear fluids.


[Co-operation among T cells in the development of cell-mediated cytotoxicity]. Lethally iradiated F1 hybrid mice were given an intravenous injection of parental strain spleen cells. Six days later, their spleen cells were used as the effector cells to measure the in vitro cell-mediated cytotoxicity (CMC) of the parental cells. The treatment of  the parental donors with hydrocortisone resulted in a marked decrease of the capacity of their spleen cells to produce a CMC reaction, while the treatment with anti-thymocyte serum (ATS) resulted in an almost complete loss of such activity. The mixing of spleen cells from hydrocortisone-treated parental donors with the spleen cells from ATS-treated parental donors before injection resulted in a synergistic amplification of the cytotoxic response. These results demonstrated a synergistic interaction between hydrocortisone resistant T cells and ATS-resistant T cells in the generation of cytotoxic lymphocytes.


[In vitro differentiation of B lymphocytes]. In order to find if lymphoid colony-forming cells in the mouse are precursors of lymphocytes or are more differentitaed cells with a high proliferative capacity, their distribution between spleen and lymph node was compared to that of mitogen-sensitive B lymphocytes and that of precursurs of B lymphocytes assayed in mass cultures. The results and the responses to culture conditions suggest that these cell populations are different from each other.


[Genetic control of the H-2 region of the cell surface: cationic amino groups in the periphery of T lymphocytes]. Spleen lymphocytes and erythrocytes from congenic mice of diffrent haplotypes were characterized on a precise biophysical basis (the anodic electrophoretic mobility, EPM) to correlate any subtle differences in the cell surface topochemistry with the H-2 specificity. Spleen T lymphocytes from A.CA (H-2f) and A.SW (H-2s) mice exhibited high values EPM, which were significantly different. In contrast, significant differences in the EPM of B cells and erythrocytes were not observed. Cell electrophoresis of spleen T lymphocytes (without " contaminating " B cells), before and after the chemical modification of the cell surface by treatment with small/non-toxic concentrations of maleic anhydride, showed the number of lysine side chain amino-groups in the periphery of cells with H-2f specificity to be about twice those on cells with H-2s haplotype. Such a difference was observed both in the case of premature T lymphocytes and mature T lymphocytes. The difference in the number of cationogenic amino-groups in the cell periphery contributing a positive charge, would explain the oberved difference in the EPM of H-2f and H-2s spleen T lymphocytes, and suggest that the macromolecules coded by the H-2 genes or other genes under H-2 control lead to delicate differences in the chemical composition of the surface membranes of cells of the two H-2 haplotypes, expressed only on high EPM lymphocytes of spleen (T or T-like cells).


[Determination of anti-DNA and anti-RNA antibodies in serum and CSF by a new counterimmunoelectrophoresis method]. A new quantitative counterimmunoelectrophoresis technique allows the determination of anti-DNA and anti-RNA antibodies in the serum and the unconcentrated CSF. Normal sera (but not normal CSF) presents anti-DNA and anti-RNA antibodies probably of IgG type. Pathological results (elevated serum values and/or presence of anti-nucleic  antibodies in CSF) are observed in some neurological diseases especially SSPE, multiple sclerosis and, generally speaking infectious diseases. A very significant correlation exists between the presence of anti-nucleic antibodies in CSF and a local (intrathecal) IgG synthesis. The same correlation is observed with oligoclonal aspect in CSF. In some cases a percentage of anti-nucleic antibodies higher in CSF than in serum may indicate the persistence of an infectious agent inside the central nervous system.


[Suppressor cells in allergic encephalomyelitis]. The induction of EAE in Lewis rats by basic protein (BP) is suppressed by the transfer of non-draining lymphnode cells from cured animals. The activation of draining lymphnode cells of these cured animals by BP, PHA or ConA is decreased with the addition of non-draining lymph node cells from the same rats.


[In vitro stimulation of human T and B lymphocytes by lipopolysaccharide (LPS)]. The appearance of cells (CFC) having the property to cluster several layers of sheep red blood cells around themselves has been used in our laboratory as a marker for T cell activation. In this study, enumeration of stimulated T cells was carried out by this technique, whereas enumeration of B cells was carried out with surface Ig staining using fluorescein-labelled anti-Ig antibodies or F(ab)2 anti-Ig. Lymphocytes were stimulated in vitro for various lengths of time with the polyclonal mitogen PWM, the specific antigen Varidase and LPS added at culture initiation or 16 hours after beginning of culture. Our results confirm that human lymphocytes preincubated for 16 hours before addition of LPS give rise to higher numbers of CFC and blast cells, In all cases, less than half of these blasts reacted with the F(ab)2 anti-Ig, This suggests that under these conditions, LPS is not a mitogen specific for human B cells.


[Anti-actin and anti-tubulin antibodies in the serum of non-immunized animals]. The preparation and the purification of anti-action and anti-tubulin antibodies is reported. The occurrence of low amount of IgG anti-tubulin was also found in the sera of non-immunized animals from various species. The staining of the cellular network of microtubules as well as of tubulin paracrystals was observed with both induced and natural antibodies.


[Induction of anti-glomerular basement membrane antibodies in BN rats: genetic control]. Mercuric chloride induces anti-glomerular basement membrane antibodies in Brown Norway rats  (Ag B3) and not in Lewis rats (Ag B1). Studies on (Lewis X BN) F1 and F2 and with back-crosses (Lewis X BN) F1 X Lewis demonstrate a genetic control for this immune response. This genetic control probably depends on two non-linked, autosomal and dominant genes. One of these genes is linked to the major histocompatibility locus.


[Antinuclear antibodies and PHA response in rheumatoid arthritis]. We have studied the in vitro PHA response of two groups of rheumatoid arthritis patients differing only in the presence or absence of antinuclear antibodies. The response was depressed in positive patients and normal in negative patients. Differences in peripheral blood mononuclear cell sub-populations or lymphocytotoxic antibodies do not seem to explain this observation. Simple antinuclear antibody screening could serve as a simple method to identify a sub-group of immunodepressed rheumatoid patients as potential candidates for immunostimulating therapy.


[Modulation of lymphocyte proliferation by serum factors and lipopolysaccharide]. The in vitro proliferative response of rat lymphoctes culitivated in increasing concentrations of calf serm (LCS) was measured by the incorporation of 3H-thymidine. Results showed that in contrast to the response of PHA, the response to concanavlin A (conA) was greatly dependent on the concentration of serum in the medium. Kinetics of the response of ConA indicated that increasing concentrations of LCS unblocked the non-response to supraoptimal doses of the mitogen. The supportive effect of LCS was not due to an increase in cell viability and was abolished when serum was dialyzed. By contrast, lipopolysaccharide (LPS) exerted an adjuvant effect on the response to optimal and suboptimal concentrations of ConA without unblocking the non-response to high doses. LPS facilitated the response to ConA of a distinct subpopulation of T cell isolated by separation on nylon wool columns. This in vitro model allowed us to study some factors which may be implicated in tolerance and immunity.


[The role of thymic microenvironment in T-cell maturation]. The role played by different components of thymic microenvironment in T-cell-maturation is examined: antibodies to a soluble thymic factor (STF) were thus shown to inhibit T-cell maturation in the chicken while incubation of bursal "null" cells with STF could induce the differentiation of some of them into T cells. In addition to STF, whose properties resemble those of other soluble thymic factors, an insoluble thymic factor (ITF) is described: it is localized mainly in membranes associated with medullary blood vessels, and its injection to mice provokes an influx of marrow stem cells into the thymus.


[Physiology and pathology of the HLA complex (author's transl)]. The functions of the genes included in the HLA complex have been studied mainly through the allogenic response, in vitro and in vivo. The sequence of this response was established thanks to primary and secondary MLC and CML. It appears that at least two clones of T lymphocytes are involved, the first in the non-self recognition through HLA-D differences, and the second in immunization against the HLA-A and B incompatibilities. Many associations between HLA and diseases have been found. They can be classified in three categories according to their associations with HLA-B, D, or with another gene of the complex. They are true experiments of nature which will give clues to the physiological functions of the HLA complex genes.


[Regulation of lymphocyte responses in vitro: inhibitory effects of rat serum]. Previous results on the potentiation by cytochalasin B (CB) of lymphocte responses in vitro, particularly the requirement for serum for this potentiation, prompted us to undertake the present study on inhibitory effects of autologous serum on rat lymphocyte activities. Main results mirror the inverse effect of CB: maximal inhibition is obtained at suboptimal doses of PHA; inhibitory effect bears essentially on early events of activation; high cell density is of prime importance. In contrast to CB, serum affects more 3H-TdR incorporation than blast transformation. Therefore, CB and some serum component(s) could have inverse effects on a single regulatory mechanism: suppressive cellular interactions.


Serial studies of numbers of circulating T and B lymphocytes in children with acute lymphoblastic leukaemia. Serial studies of numbers of circulating T and B lymphocytes at monthly intervals in children with acute lymphoblastic leukaemia showed a marked fall in the number of B cells, relatively greater than that of T cells, early in the course of maintenance chemotherapy and immediately after a course of cranial irradiation. The fall in the number of B cell is not a consequence of long-term chemotherapy, and is possibly related to a specific event such as cranial irradiation.


Causes of death in aortocoronary bypass surgery: experience with 1,000 patients. Of the first 1,000 consecutive patients in our unit to receive aortocoronary bypass grafts, 108 have died: 32 at operation, 16 in hospital, and 60 late. Of 343 patients who had a normal ventricle, only 1 (0.29%) died at operation, and 2 of the 8 late deaths were noncardiac in cause. Most operative deaths resulted from low cardiac output, and most later deaths were caused by congestive heart failure. A study of the relation of various clinical and operative factors with mortality found that patients with congestive heart failure who underwent valve replacement and bypass grafting had the worst prognosis (73% mortality) while those undergoing bypass grafting with Class III or IV ventricular function (as we define it) and congestive heart failure were next (49% mortality).


[Cellular interaction in the pokeweed-mitogen induced terminal differentiation to polyclonal immunoglobulin production in human B lymphocytes in vitro]. The differentiation of human B lymphocytes in vitro into Ig secreting cells, as measured by a radioimmunoassay rendered specific to IgG and IgM, in response to a polyclonal stimulant, requires the participation of several cellular types. Upon poleweed-mitogen stimulation, B-cell enriched and monocyte containing cell suspensions prepared by elution of nylon wool adherent cells, when mixed with various concentrations of T cells purified by filtration through nylon wool column and depletion of EAC-rosette forming cells, synthesize 5 to 20 times more Ig than non separated lymphocytes. These experiments which demonstrate the cooperation of certain T cells also suggest that other cells eliminated by nylon wool adherence act as suppressor cells. The cooperation of these T cells is independent of their proliferation and can be obtained with allogeneic T cell.


Tissue uptake of isotopically labeled aprotinin in early myocardial ischemia. The tissue uptake of 3H-aprotinin was studied in anesthetized cats during acute myocardial ischemia (MI) 1 an 2 hr after injection of the tracer. Several tissues exhibited a rapid uptake of the protease inhibitor. Kidney, lung and liver demonstrated the greatest uptake with tissue/plasma ratios of 1.6 to 4.8. Spleen, adrenals, intestine, heart and pancreas exhibited tissue/plasma ratios of 0.28 to 0.58, whereas abdominal aorta, skeletal muscle and omentum had tissue/plasma ratios below 0.17. The rate of clearance of 3H-aprotinin from cat plasma was unaltered by myocardial ischemia. Although ischemic myocardial tissue took up less aprotinin than the non-ischemic myocardial tissue in the same hearts, ischemic tissue accumulated significant amounts of aprotinin relative to the non-ischemic region (82%). These data show that aprotinin reaches ischemic myocardial tissue during the first 2 hr of acute ischemia and would be available to antagonize some of the proteases which may be liberated during these critical early hours of the ischemic process.


Lupus-like syndrome associated with carcinoma of the breast. Two patients with locally advanced carcinoma of the breast had radiation therapy as primary treatment. Within one year, a lupus-like syndrome developed characterized by pneumonitis, pleural effusion, and positive fluorescent antinuclear antibody (FANA) reaction and lupus erythematosus (LE) preparation. Pericarditis developed in one patient and leukopenia in the other. The bilateral pulmonary disease, serological abnormalities, and rapid and sustained response to administration of prednisone made the diagnosis of systemic lupus erythematosus more likely than radiation-induced disease or metastic carcinoma. Radiation to normal and/or malignant tissue may have initiated an immunological response leading to a lupus-like syndrome.


[Cellular interactions in the lymphocyte response to PHA in old people]. Peripheral blood lymphocytes (PBL) from the same number of old subjects (OS) and young subjects (YS) have been separated into subpopulations of T cells (T1 and T2 fractions) and B cells. Phagocytes were removed by carbonyl iron. The recovery in T1 is reduced in the OS. Their PHA response is inhibited by monocytes but not by polynuclears (PN). The response of their peripheral T cells is not reduced but it is not enhanced by adding PN. There is a normal T-B cell interaction in the response to PHA. It is suggested that the impaired PBL response to mitogens is secondary to the reduction of their content in T1 lymphocytes.


Ultrastructure of the spleen in malignant histiocytosis. We examined the ultrastructure of the spleen surgically removed from a patient with the in vivo diagnosis of malignant histiocytosis. The findings showed sinuses greatly dilated and lined by large atypical histiocytic cells. Erythrophagocytosis was prominent. These findings, as well as the histologic features of the bone marrow and later autopsy specimens, confirmed the diagnosis of malignant histiocytosis. The somewhat unusual confinement of histiocytes to sinusoids raised the possibility that this may represent a rare subvariant, histiocytic sinus reticulosis, first described by Robb-Smith in his original paper.


Ultrastructure in the differential diagnosis of pulmonary histiocytosis and pneumocystosis. A child with histiocytosis X initially diagnosed at the age of 4 months had a series of pulmonary biopsies later in the course of the disease. The specimens were examined by light and electron microscopy. The primary disease was complicated by Pneumocystis carinii pneumonia. This study demonstrates the limitation of light microscopy and the necessity of ultrastructural examination to verify the simultaneous occurrence of an infiltrative disorder such as histiocytosis X in the presence of an infection.


[Role of H-2 region in cytolysis of viral induced lymphomas by T lymphocytes]. The cytolyse of lymphoma cells by anti-MSV-CTL requires an H-2 identity on CTL and target cells. It can be limited to D or K antigens. An altered cells hypothesis is the more likely hypothesis in H-2a or H-2d tumour cells. However the D antigen alone is involved in H-2b tumours Arguments are given which supports the existence of Ir genes controlling the formation of CTL against H-2Dd modified by MSV.


Lattice corneal dystrophy. Report of an unusual case. The clinical, histochemical, light and electron microscopic evaluation of a case of lattice corneal dystrophy, appears clinically as an atypical granular dystrophy. There is structural and histochemical differentiation of the two dystrophies. Electron microscopy is often an invaluable aid in establishing a definitive diagnosis. The possible sources of the filamentous material found in lattice corneal dystrophy are discussed. It seems that not only keratocytes, but also corneal epithelial cells, occasionally may have the ability to elaborate the abnormal material that is considered to be amyloid in nature.


T-lymphocytes and survival of head and neck squamous cell carcinoma. The thymus-dependent lymphocytes (T cells) were enumerated in the peripheral circulation of 38 patients with histologically demonstrated squamous cell carcinoma of the head and neck. We have previously shown that this "total" T-cell count correlates well with degree of tumor involvement. A lower percentage of T cells were shown in patients with more advanced malignant neoplasms. Here we present follow-up data on these patients to evaluate the efficiency of the T-cell test in determining survival prognoses. We found no evidence that results of this test can extend prognostic abilities above those based on clinical staging. The survival data from six patients treated with a chemoimmunotherapy regimen of BCG vaccine, methotrexate sodium, and isoniazid did not demonstrate an increased survival time compared to patients at similar clinical stages who were treated by conventional use of surgery and irradiation.


[Duration of postacceleratory nystagmus in theory and experiment (author's transl)]. For special questions the validity of models has to be verified in each case. One possibility for controlling the model of the vestibulo-oculomotor system (completed with a neuronal integrator) which is used for automatic quantitative nystagmus analysis is the duration of the postacceleratory nystagmus. Theoretically for this parameter an upper limit exists which is independent of stimulus strength and influenced only by the system parameters and stimulus duration. Several experimental studies are compared with the theoretical calculations. As a result, the conception of the model is confirmed; however, nystagmus duration appears to be a valuable characteristic only under certain experimental conditions. For this reason, nystagmus duration is not considered as a parameter of the quantitative analysis.


[Equilibriometric findings in partially blind and blind children (author's transl)]. 26 of both blind or partially blind children were subjected to equilibriometric tests. By way of a vestibular-ocular test they were given the Rotatory-Intensity-Damping test. During the tests the per and postrotatory nystagmus reactions were electronystagmographicly registrated. For the vestibular-spinal tests the Unterberger's stepping test with photographic registration of the body-sway in the Cranio-Corpo-Gram was used. In most of the children you could identify a definite per and postrotatory reaction in spite of considerable spontaneous reactions. The strong eyelid movements of these patients, the intensive spontaneous deviations and diminished corneo-retinal potential made precise judgement of the electronystagmogram difficult. Comparison between the blind and partially blind children enabled the differences to be objectified. Blind-born children have a higher spontaneous activity, slightly diminished per and postrotatory nystagmus reactions and a diminished bodyequilibrium. These results can be explained on one side by habituation and on the other side by efferent structures, which have an inhibitory effect on the vestibular input.


Prostaglandin E treatment of NZB/NZW mice. NZB/NZW F1 hybrid mice were treated with pharmacologic doses of prostaglandin E1 (PGE1) (200 microng subcutaneously either once or twice daily) from 6 through 52 weeks of age. PGE1-treated mice were protected against development anemia, clinical nephritis, and death. At 52 weeks 18 of 19 treated mice were alive, wherase only 2 of 19 untretreated control mice were alive. None of the 10 mice treated with PGE1 twice daily exhibited significant (greater than 2+) proteinuria at 1 year of age. PGE1 treatment did not prevent development of antibodies to nuclear antigens. The data also suggest that survival of NZB/NZW mice is prolonged when treatment with PGE1 is begun at 24 weeks, an age at which mice already show evidence of nephritis. Thus all 6 mice treated with PGE1 (200 microng sc twice daily) from 24 weeks were alive at 52 weeks, whereas only 2 of 6 untreated control mice were alive. The mechanisms whereby PGE1 treatment influences the course of disease in NZB/NZW mice are not known.


Aprotinin and growth of Walker 256 carcinosarcoma in the rat. Growth of the Walker 256 carcinosarcoma implanted within various sites in Spraque-Dawley rats was investigated in animals receiving twice daily i.p. injections of the antiprotease aprotinin. Although administration of aprotinin partially attenuated the growth and lethality of i.p. tumour, no effect of aprotinin was found on intramuscular tumour development. Furthermore, we were unable to demonstrate unequivocal growth inhibition by aprotinin of lung tumour colonies from i.v. injection of tumour cells. Histological examination of intramuscular and pulmonary tumours revealed little evidence of host cellular immune response in either saline- or aprotinin-treated rats.


Spectrum of von Willebrand's Disease: a study of 100 cases. Italian Working Group. The clinical picture, family history and laboratory findings of 100 patients with von Willebrand's disease (VWD) have been studied in Italy in a multicentre survey from two rural areas with a known high incidence of the disease and from two large cities (Rome and Milan). Bleeding time, procoagulant factor-VIII (VIIIAHF) assay, platelet retention and PRP-ristocetin aggregation were measured in each centre, and plasma samples were frozen and subsequently assayed for factor VIII-related antigen (VIIIAGN) and ristocetin co-factor (VIIIVWF) in one laboratory (Milan). On the basis of the inheritance pattern, clinical severity of the disease and laboratory findings, patients with VWD were separated into two groups. In 17 patients the absence of a family history of bleeding, a high incidence of parental consanguinity and involvement of both sexes suggested an autosomal recessive mode of inheritance; the unusual severity of the disease with markedly abnormal results of all six laboratory measurements (and frequent reduced levels of VIIIAGN and VIIIVWF in the unaffected parents) were consistent with the homozygous state. In 83 patients, the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity. In these, VIIIVWF was usually much lower than VIIIAHF and VIIIAGN. The findings suggest that although some patients may present with simultaneous abnormalities of all six studied laboratory measurements, the majority show a variation in the spectrum of the abnormal results, without any obvious simple pattern.


Synthesis and characterization of a pancreatic trypsin inhibitor homologue and a model inhibitor. The synthesis and characterization of protein proteinase inhibitor homologues with variations in the amino acid composition in the vicinity of the reactive site should aid the understanding of the mechanism by which inhibition of enzymatic activity occurs. A homologue inhibitor in which the reactive-site residue Ala-16 of basic pancreatic trypsin inhibitor (Kunitz) (BPTI) is replaced by Phe has been synthesized to study the effect of this replacement on the dissociation constants of the enzyme-inhibitor complexes. The replacement of Ala-16 by Phe causes a dramatic increase in the K1 value of the trypsin-BPTI complex while that of the chymotrypsin-BPTI complex remains essentially the same. This cannot be explained simply in terms of increased steric crowding. The Phe replacement probably causes a small change in the local conformation of the reactive site of the inhibitor which leads to a large decrease in the stability of the very tight trypsin-BPTI complex. This conformation change apparently can be tolerated in the less tightly bound chymotrypsin-BPTI complex. On the basis of the known structure of BPTI, a cyclic heptadecapeptide containing one disulfide bond was synthesized as a model inhibitor in order to determine if a smaller peptide can be designed to act as a highly efficient inhibitor for trypsin. This heptadecapeptide which contains all of the amino acid residues of BPTI taking part in the interaction of the proteinase inhibitor with trypsin binds 3 X 10(7) time more weakly to the enzyme than native BPTI does. It thus appears that even though only a small part of the inhibitor molecule enters directly into interaction with the enzyme, the remaining portions of the molecule which hold the structure of the inhibitor rigid are essential for the strong interaction.


Further evidence for dissipative energy migration via triplet states in photosynthesis. The protective mechanism of carotenoids in Rhodopseudomonas spheroides chromatophores. The protection action of carotenoids against irreversible photodestruction was discovered in photosynthetic bacteria by Stanieda and coworkers. In green plant material it was found by Wolff and Witt (1969) Z. Naturforsch, 24b, 1031-1037 and (1972) Proc. 2nd. Int. Congr. Photosynthesis Res. Stresa (Forti, G., Avron, M. and Melandri, A., eds.), Vol. 2, pp. 931-936, Dr. W. Junk, N. V. Publ. The Hague) that the formation of special carotenoid triplet states (via very rapid energy transfer from excited chlorophylls) and their fast radiationless decay in tau1/2 approximately 3 microns is at least one mechanism for the protective action of carotenoids to irreversible photooxidation of the chlorophylls. Hence, it is anticipated that the same mechanism might be realized also in bacteria. The present study gives evidence for such a "triplet valve" to be established also in bacteria. This conclusion was derived from the following observations: 1. The light-induced difference spectrum shows a bleaching of a carotenoid at three characteristic wavelength between 400 and 500 nm. A positive peak around 533 nm indicates the formation of a carotenoid triplet state. 2. The absorption changes can be induced by red light which excites only bacteriochlorophyll. This indicates an energy transfer from bacteriochlorophyll to carotenoids. 3. The light-induced carotenoid triplets decay radiationless in 3 microns in air-saturated aqueous suspensions of the chromatophores. 4. The carotenoid triplet formation occurs only at actinic flash intensities where the photosynthesis becomes saturated. 5. Addition of dithionite, which blocks photosynthesis, markedly increases the extent of carotenoid triplet formation. The different types of exciton migration within the photosynthetic unit are discussed, especially the routes leading to the dissipation of excess excitation energy.


Selective inhibition of initial polyadenylation in isolated nuclei by low levels of cordycepin 5"-triphosphate. The effect of cordycepin 5'-triphosphate on poly(A) synthesis was investigated in isolated rat hepatic nuclei. Nuclei were incubated in the absence and presence of exogenous primer in order to distinguish the chromatin-associated poly(A) polymerase from the "free" enzyme (Jacob, S.T., Roe, F.J. and Rose, K.M. (1976) Biochem. J. 153, 733--735). The chromatin-bound enzyme, which adds adenylate residues onto the endogenous RNA, was selectively inhibited at low concentrations of cordycepin 5'-triphosphate, 50% inhibition being achieved at 2microng/ml. At least 80 times more inhibitor was required for 50% reduction in the "free" nuclear poly(A) polymerase activity. Inhibition of DNA-dependent RNA synthesis also required higher concentrations of the nucleotide analogue. These data not only offer a mechanism for the selective inhibition of initial polyadenylation of heterogeneous nuclear RNA in vivo by cordycepin, but also provide a satisfactory explanation for the indiscriminate effect of the inhibitor on partially purified or "free" poly(A) and RNA polymerases.


Mammalian adenylosuccinate lyase. Participation in the conversion of 2'-dIMP and beta-D-arabinosyl-IMP to adenine nucleotides. Adenylosuccinate synthetase (EC 6.3.4.4) from rabbit muscle efficiently catalyzes the formation of 2'-deoxyadenylosuccinate and beta-D-arabinosylade-nylosuccinate from 2'-dIMP and beta-D-arabinosylIMP (Spector, T. and Miller, RL. (1976) Biochim. Biophys. Acta 445, 509-517). These novel analogs of adenylosuccinate were synthesized with this enzyme and their kinetic constants were determined with adenylosuccinate lyase purified from Ehrlich ascites cells. 2'-Deoxyadenylosuccinate and beta-D-arabinosyladenylosuccinate were readily cleaved to 2'-dAMP and beta-D-arabinosylAMP, respectively. Their Km values were similar to that of adenylosuccinate (3-6 micronM) and their substrate efficiencies (V/Km) were 120 for 2-deoxyadenylosuccinate and 32 for beta-D-arabinosyl-adenylosuccinate, compared to a value of 100 for adenylosuccinate. The products of the reactions, 2'-dAMP and beta-D-arabinosylAMP, were competitive inhibitors with Ki values of 5 and 87 micronM, respectively. ATP and ADP were considerably weaker competitive inhibitors with Ki values of 200-300 micronM. IMP, GMP, xanthosine 5'-monophosphate, 6-thioIMP and 6-thioGMP had Ki values greater than 200 micronM.


Effect of psychotropic agents upon the blastogenic response of human t-lymphocytes. Antischizophrenic agents, phenothiazine and nonphenothiazine, inhibit the transformation of the T-lymphocyte in vitro. This inhibition occurs only in the early event and is neither competitive with dopamine, nor appears to involve Na+/K+ adenosine triphosphatase. RNA synthesis is more sensitive to the inhibitory effect than DNA or protein synthesis. This leads to the conclusion that chlorpromazine may act by inhibiting the synthesis of newly formed RNA, and subsequently, transformation, rather than by alteration of the cell membrane.


An image intensifier aid for chronic night blindness. Working with the Retinitis Pigmentosa Foundation, ITT has designed an image intensifier monocular specifically for application as a prosthetic aid for persons suffering from chronic night blindness as a result of retinal degenerations. A description of the instrument along with the rationale for its major design points is given and its applications illustrated. The first few of these instruments were delivered earlier this year and limited production has been started.


[Cytotoxic serum against B-lymphocytes obtained by immunization with bone marrow cells]. Immunization of rabbits with the bone marrow cells of intact mice permitted to obtain antisera selectively reacting with the cells of the bone marrow origin. A method of obtaining the anti-B-sera by immunization of animals directly with the bone marrow cells permitted to exclude irradiation and thymectomy of mice, this serving as necessary steps of the methods described formerly.


[Antibody formation and B-cell migration from bone marrow to spleen in mice under conditions of stimulation and suppression of erythropoiesis]. The effect of erythropoietic stimulation and suppression on the production of antibody-forming cells (AFC) in the spleen and on the B-cell migration from the bone marrow to the spleen was investigated in the CBA mice. Erythropoiesis stimulation proved to sharply increase the AFC count in the spleen and the B-cell migration from the bone marrow to the spleen 1 and 4 days after the bleeding. Erythropoiesis suppression resulted in a slight increase of the AFC count in the spleen 4 and 7 days after the transfusion of syngeneic red blood cells. However, the erythropoietic suppression inhibited the B-cell migration from the bone marrow to the spleen. Possible mechanisms of the effect of the erythropoietic stimulation and suppression on the antibody production are discussed.


[Human, guinea pig and rat lympocyte rosette formation with spermatozoids]. In the thymus, spleen and bone marrow of adult guinea pigs, 14--30-week human fetuses, and the peripheral blood of sterile men there were found cells capable of forming the rosettes with homo- or heterologous spermatozoa (RFC). Development of autoimmune orchitis after the trauma of the rat testis or after the guinea pig immunization with the testicular homogenate mixed with complete Freund's adjuvant caused the appearance of RFC with spermatozoa in the thymus and the spleen of rats, and an increase of their number in the lymphoid organs of guinea pigs. Such treatment did not influence the quantity of sheep-cell rosettes in the lymphoid organs of rats and guinea pigs. A possibility of using the detected capacity of animal and human lymphocytes to form spontaneous and immune rosettes with the spermatozoa to test the degree of lympocyte differentiation and their sensitisation to the spermatozoa antigens after the spermatogenesis distrubances of the autoimmune nature is discussed.


Demonstration of granulopoietic factor(s) in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue. A human lung cancer (OTUK-tumor) was transplanted serially to nude mice, which invariably developed a marked neutrophilia. In order to analyze this phenomenon, in vitro agar culture studies were carried out. A three- to fourfold increase of colony-forming units in culture was observed in the femurs of these nude mice. Moreover, the plasma of nude mice bearing this tumor, as well as the tumor extract, had a significantly higher colony-stimulating activity on mouse bone marrow cells than appropriate controls. This activity had the property to stimulate granulocyte and/or mixed cell type colonies rather than mononuclear cells. This activity was also demonstrated, in a dose-dependent way, on normal human bone marrow cells. These findings indicated that the OTUK-tumor produced human granulopoietic colony-stimulating activity, which may have stimulated granulopoiesis in vivo as well.


Growth of bone marrow cells of normal and Rauscher virus infected mice in suspension cultures stimulated by CSA. Bone marrow cells of normal and Rauscher virus (RLV) infected CBA/J mice were cultured under stimulation by postendotoxin serum. Cellular morphology and the number of granulocytic committed stem cells from day 1-5 after the onset of the cultures were studied with different amounts of postendotoxin serum added. There was a good correlation between total cellularity, the number of immature granulocytopoietic cells and the number of colony forming unit cells (CFUc) in suspension with the amount of postendotoxin serum. Postendotoxin serum delayed the appearance of macrophages in the cultures for 1-2 days. Cells from RLV infected animals showed a rather normal differentiation of the morphological recognisable cells 5 and 21 days after infection, but the CFUc survival in vitro 3 and 5 weeks after infection was reduced.


The effect of two pesticides, Miedzian 50 and Gesagard 50, on the development of tadpoles of Rana temporaria. Tadpoles of the frog, Rana temporaria, in two developmental stages were subjected to the action of aqueous suspensions of two pesticides--Miedzian 50 and Gesagard 50. The changes caused by these substances pertain chiefly to the alimentary canal, brain, and muscles, and are connected with the developmental stage of the animals. Miedzian 50 caused a partial sytolysis in the cells of the intestinal epithelium and the parenchyma of the liver. Gesagard 50 was more toxic; under its action strong degenerative changes were obtained in the alimentary canal and the brain. Also, disorders in the development of tadpoles were observed. These consisted in a partial inhibition of growth and a retardation of the process of completion of the operculum as compared with control animals.


A comparison of the reflex organization of thoracic and lumbar segments in the frog spinal cord. Both lumbar dorsal root (DR) primary afferents and descending fibers in the lateral column (LC) make monosynaptic connections with ipsilateral lumbar motoneurons in the frog spinal cord. We have determined that LC fibers also make monosynaptic connections with thoracic motoneurons, while thoracic primary afferents do not. The central reflex time (CRT) for the lumbar DR-VR pathway was 2.5 +/- 0.3 msec, but the CRT for the thoracic DR-VR pathway was 8.5 +/- 2.6 msec. By using a conditioning-test paradigm we have been able to determine that the earliest sign of segmental synaptic transmission in thoracic motoneurons occurs only after a delay of 6.1 +/- 0.9 msec. These results correlate very well with the different morphological characteristics of lumbar and thoracic segments. We have also investigated the central organization of lumbar and thoracic segments and found that the segmental polysynaptic input to motoneurons is more diffuse in thoracic than in lumbar segments. The intersegmental reflexes between thoracic and lumbar segments provide additional evidence for a more diffuse organization in thoracic segments.


Metabolism of tryptopan and serotonin by the chick pineal gland in organ culture. Marked differences were seen between the metabolism of L-[3-14C] tryptophan and of [2-14C]serotonin by the intact chick pineal gland in organ culture. The major metabolite of tryptophan recovered by our procedures was melatonin, which accounted for about half the radioactivity recovered as metabolic products. In contrast, the principal product of serotonin metabolism recovered was hydroxyindoleacetic acid, and the yield of products derived through monoamine oxidase (EC 1.4.3.4) activity vastly exceeded that of melatonin. Metabolism of tryptophan yielded a much larger proportion of methlated metabolites among the products recovered than did metabolism of serotonin. However, the yield of methoxyindoleacetic acid from serotonin was greater than that from tryptophan. Serotonin formed endogenously and serotonin supplied exogenously appear to enter two or more largely distinct metabolic pools.


Thymoma immunological and ultrastructural characterization. A 69-year-old man with a mediastinal mass was found to have atypical lymphoid cells in peripheral blood and bone marrow. Light and electron microscopic studies showed that the mediastinal mass was a thymoma. B- and T-cell differentiation and PHA responsiveness in the tumor and peripheral blood were consistent with T-cells. After excision of the tumor and a course of radiotherapy  the B/T ratio and PHA responsiveness in peripheral blood returned to normal while the atypical lymphocytes disappeared from circulation.


Studies of T, B, and null lymphocytes during the course of acute lymphocytic leukemia. The distribution of T, B and null lymphocytes was studied in the peripheral blood (PB) of 34 children with acute lymphocytic leukemia (ALL), at diagnosis and during the course of their disease. All patients received the same chemotherapy. At diagnosis, the proportion and absolute numbers of T lymphocytes fell into 2 groups, a "low" group (medians 8%, 318/mm3) and a "normal" group (medians 60%, 1405/mm3). Patients with a low proportion of T cells tended to have a high proportion and absolute number of null cells (correl. coeff. r = 0.94). This group has had high white blood cell counts (median = 29,600/mm3) and a high proportion of blasts (84%). During remission, the proportion of T cells returned toward normal (40-75%) in both groups. Four patients in the low T group relapsed; T cells again fell to low levels and returned to normal in response to new therapy. Three interpretations of these observations are suggested: 1) Active leukemia may cause normal lymphocytes (T cells and to a lesser degree B cells) to lose their surface markers; 2) Acute leukemia may inhibit maturation of normal lymphoid cells, and thus T or B markers are not sufficiently developed to be detectable; and 3) Cells without surface markers (null cells) may be a part of the malignant population, even though they are not morphologic blasts. Further studies are necessary to test these hypotheses.


Lymphoblasts with T-cell markers in five girls with acute lymphocytic leukemia. In previous reports, children with acute lymphoblastic leukemia (ALL), who presented with T-cell markers on their lymphoblasts (T-lymphoblasts), have been predominantly older boys often with a mediastinal mass. These children are thought to constitute a subgroup of childhood ALL that has the poorest prognosis. Here, we report five girls with ALL, who presented with T-lymphoblasts but without a mediastinal mass. All responded well to chemotherapy and three of five are in maintained remission 21-33 months after diagnosis. The fourth patient died while in remission of causes other than leukemia and the fifth relapsed and died of infection two years after diagnosis. These observations suggest that girls with T-lymphoblasts may not have an adverse prognosis.


Angio-immunoblastic lymphadenopathy terminating as Hodgkin's disease. The clinical course of a 33-year-old man with generalized lymphadenopathy bearing all physical, laboratory and histologic characteristics of "angio-immunoblastic lymphadenopathy with dysproteinemia" (AILD) is described. Therapy was without significant benefit and the patient died 22 months after initial diagnosis. At autopsy in addition to the characteristic cellular polymorphism of AILD, numerous Hodgkin's cells and Sternberg-Reed cells were identified in the lymph nodes and spleen. Pleomorphic cellular infiltrates containing an increased number of immunoblasts and some giant cells were found also in the portal spaces of the liver. The evolution of Hodgkin's disease (H.D.) from AILD suggests that the latter may have represented a reaction to the agent which causes H.D..


Effect of Corynebacterium parvum on colony-stimulating factor and granulocyte-macrophage colony formation. Because Corynebacterium parvum has tumor-inhibitory properties and stimulates granulocyte-macrophage production, it may have clinical value in combination with chemotherapy. The leukopoietic effect of killed suspensions of C. parvum was studied in mice using the technique of in vitro clonal culture of hematopoietic cells. After C. parvum injection, there was a prompt, sustained elevation of serum colony-stimulating factor followed by an increase in granulocyte-macrophage precursor cells in the spleen and increases in blood mononuclear and granulocyte cells. Colony-stimulating factor production is suggested as a major mechanism of stimulation of granulocyte-macrophage proliferation by C. parvum. Since rapidly proliferating hematopoietic cells may have increased sensititity to cytotoxic agents, the details of hematopoietic stimulation by C. parvum may be critical in the sequential timing of combined C. parvum and chemotherapy treatment to obtain maximal tumor inhibition and minimal hematopoietic toxicity.


Effect of glucan on granulopoiesis and macrophage genesis in mice. Glucan, a potent reticuloendothelial stimulant, is a glucopyranose polysaccharide derived from zymosan. Because of glucan's potential as an immunotherapeutic agent, we performed studies in order to determine its effect on granulopoiesis and macrophage production in mice. One week after the i.p. injection of 4 mg of glucan, there was a tenfold increase in colony-forming cells in the spleen and approximately a twofold increment of cells in the bone marrow and the peritoneal cavity capable of colony formation in vitro. There was a relative and absolute increase in the number of pure macrophage colonies from bone marrow and spleen. The total macrophage content in spleen, peritoneal cavity, and bone marrow as also increased in the treated mice. Serum from glucan-injected mice had high colony-stimulating activity levels, and the peritoneal macrophages elaborated increased colony-stimulating activity in vitro as compared to controls. Peripheral white blood cell counts were two times greater than those of control in the glucan-treated mice. These studies indicate that glucan administration results in increased granulocyte and macrophage production. The enhanced leukopoiesis is probably mediated in part by augmented release of colony-stimulating activity from macrophages. These observations suggest that the use of glucan as an immunotherapeutic agent can result in an increased number of available effector cells.


Enantiomeric forms of 9-(5-deoxy-beta-erythro-pent-4-enofuranosyl)adenine and a new preparation of 5-deoxy-D-lyxose. Methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-beta-D-ribofuranoside (3) was obtained in three steps from D-ribose. Exchange of the isopropylidene group for benzoate groups and acetolysis gave 1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-iodo-D-ribofuranose which was coupled with 6-benzamidochloromercuripurine by the titanium tetrachloride method to afford the blocked nucleoside. Treatment with 1,5-diazabicyclo[5.4.0]undec-5-ene in N,N-dimethylformamide and removal of the blocking groups have 9-(5-deoxy-beta-D-erythro-pent-4-enofuranosyl)adenine (9). A similar route starting from methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-alpha-D-lyxofuranoside (14) afforded the enantiomeric nucleoside, 9-(5-deoxy-beta-L-erythro-pent-4-enofuranosyl)adenine (20). Methyl 2,3-O-isopropylidene-alpha-D-mannofuranoside was treated with sodium periodate and then with sodium borohydride to give methyl 2,3-O-isopropylidene-alpha-D-lyxofuranoside (11). Acid hydrolysis afforded D-lyxose. Tosylation of 11 gave methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-alpha dp-lyxofuranoside (12) which was converted into 14 with sodium iodide in acetone. Reduction of 12 gave methyl 5-deoxy-2,3-O-isopropylidene-alpha-D-lyxofuranoside which was hydrolyzed to give 5-deoxy-D-lyxose.


Fate of thymocytes: studies with 125I-iododeoxyuridine and 3H-thymidine in mice. Cortical thymocytes of young adult mice were labeled in situ with radioactive DNA precursors. As a result of cell emigration and cell death, total thymic radioactivity decreased within 8 days to 10% or less of that present on day 1. Accumulation of thymic migrants in peripheral lymphoid organs was estimated by computing the net thymus-derived radioactivity in these tissues. Thymic cell death was assessed by comparing values obtained with 125I-UdR to those acquired with 3H-TdR; The results indicate that cortical thymocytes migrate to the spleen, mesenteric lymph node, femurs and intestine; nevertheless, only a small fraction of the activity originally present in the thymus was recovered in these organs; the vast majority of newly formed cortical thymocytes apparently die after a relatively short life span. Exclusive of the fraction which dies in situ, evidence for thymocyte death is seen in bone marrow; however, most migrants appear to terminate in the intestine.


Electron microscopic study on the early histogenesis of thymus in the toad, Xenopus laevis. Sequential electron microscopic observations of thymic histogenesis in the toad, Xenopus laevis, reveal that the thymus arises as epithelial buddings of the visceral pouches at Nieuwkoop-Faber stage 40, and acquires its basic histological features at stages 48-49. In the rudiments and the surrounding mesenchyme at stages 43-45, there are non-epithelial cells with pseudopodia, abundant ribosomes, and marginated heterochromatin. These cells, possible precursor cells of thymic lymphocytes, are frequently observed to attach and pass through the basal lamina which coats the thymic rudiment. The proliferation and differentiation of large lymphocytes are evident at stage 47. During stages 48-49 the small lymphocytes, lymphoid cortex and epithelial medulla including the thymic cysts, differentiate, and vascularization occurs. The results provide an ultrastructural basis for recent experimental evidence that the thymus exerts its essential function at stages 47-48. The possibility of non-epithelial derivation of thymic lymphocytes is discussed.


The lateral hypothalamic area. An ultrastructural analysis. An ultrastructural analysis of the rat lateral hypothalamic area (LHA) was undertaken in order to provide an initial step in the characterization of this complex area which appears to participate in a number of important neural functions. The organization of the normal tuberal LHA was compared to the area following acute and chronic denervating lesions. In the normal animal, the principal features of the LHA are the presence of lateral hypothalamic neurons, a major sagittal pathway (the medial forebrain bundle, MFB) and the interposed neuropil richly populated by a variety of synaptic terminal types. Alterations in the synaptic organization of the LHA following rostral and caudal MFB lesions were most pronounced in animals with acute and chronic caudal lesions. A 10% reduction of synaptic terminals containing 800-1000 A diameter dense core vesicles and a 10% increase in terminals containing lucent core vesicles was observed in animals with caudal lesions while no significant redistribution of synaptic terminal types occurred with rostral lesions. The preliminary degeneration experiments indicate that identification of the numerous and diverse afferents to the LHA neuropil may be aided by this method but that a detailed and systematic ultrastructural analysis will be required to identify sources of input with certainty.


Report of the ad hoc committee on the indications for coronary arteriography. Prepared by the council on clinical cardiology of the American Heart Association. The purpose of this report is to aid physicians as they consider performances of coronary arteriography in individual patients. The recommendations are largely based on published reports about the procedure, coronary disease and current approaches to treatment. The fact that relevant information is accumulation rapidly has been taken into account and it is hoped that the guidelines will be adaptable in this time of change. However, the results of clinical trials of coronary bypass surgery now in progress could necessitate a revised point of view in the future. A guiding principle in preparation of this document was that the findings from arteriography should resolve diagnositic problems, or serve to evaluate patients for treatment which has known therapeutic outcomes. These goals should be readily apparent. An example is arteriography to evaluate the feasibility for coronary surgery for intractable angina pectoris. In a few areas, arteriography as preparation for coronary bypass surgery is suggested as a promising plan to deal with desperate illness, despite incomplete information about outcomes. The role of coronary arteriography is explored in various clinical syndromes which include chest pain of uncertain origin, chronic stable angina pectoris, main left coronary artery disease, unstable angina, latent coronary disease, after recovery from myocardial infarction, recurrent ventricular arrhythmias, the problem of sudden death, after aorto-coronary bypass surgery and acute myocardial infarction. Alternative opinions are mentioned in various sections of the report, but whenever possible, a concensus of the committee's opinion is given.


Detection of creatine kinase BB isoenzyme in sera of patients undergoing aortocoronary bypass surgery. Creatine kinase BB isoenzyme (CK-BB) was detected intraoperatively in 22 of 25 patients undergoing aortocoronary bypass surgery, both in the coronary sinus and in the mixed venous blood. In a group of 10 patients in whom selective intracavitary profound hypothermic arrest was used, CK-BB values were lower than in another group of 10 patients, in whom controlled ventricular fibrillation with moderate total body hypothermia was instituted. This latter group also had higher levels of CK-MB. Patients who developed acute myocardial infarction immediately prior to or during the surgical intervention had the highest CK-BB values. This enzyme appeared as early as 15 minutes after the institution of cardiopulmonary bypass and disappeared within 6 hours. It is considered that part of the BB isoenzyme in serum of patients undergoing heart surgery is of myocardial origin.


Electrochemical profile of K and Cl ions across the proximal tubule of bullfrog kidneys: a study using double-barreled ion-sensitive microelectrodes. Micropuncture study was performed in the proximal segment of bullfrog nephrons with double-barreled ion-sensitive microelectrodes to determine the electrochemical profile of K and Cl across the individual borders of tubular epithelium. The mean peritubular potential obtained was -68.4 mV, and the K activity in the plasma and the cell interior was 2.64 and 61.6 mEq/liter, respectively. The calculated equilibrium potential for K was 79.3 mV. Therefore, the cell K must be maintained by some K uptake mechanism against an electrochemical gradient of 11 mV. Further, the K activity of the tubular fluid was 2.92 mEq/liter and the actually measured PD across the brush border membrane was -55.7 mV. Since the calculated Nernst K potential is 76.8 mV, the K entry from lumen to cell must be done against an electrochemical gradient of 21.1 mV in the net. These facts might suggest a possibility of bilateral existence of K uptake mechanism in both the peritubular and brush border membranes of proximal tubular cells. In contrast, the Cl activity was measured to be 9.30, 78.0, and 72.5 mEq/liter for the cell, tubular fluid, and plasma, respectively. The Nernst Cl potentials calculated were 53.6 and 51.7 mV for the brush border and the peritubular membrane, the data being less than the actually determined values, 55.7 and 68.4 mV, respectively. Thus, the Cl ion seemed to distribute passively throughout its reabsorptive process in the bullfrog proximal tubule.


Acute gastrointestinal bleeding during experimental hypercarbia. Experimental acute hypercarbia in dogs produced significant blood loss from the upper gastrointestinal tract, as well as from the small and large intestines. At necropsy, gross and microscopic examinations demonstrated necrotizing lesions resembled the postmortem ulcerations found in some patients with severe hypercarbia. Superior mesenteric arteriograms performed in four animals shortly after onset of hypercarbia showed abnormalities consistent with vasoconstriction. Vagal inhibition by atropine and correction of respiratior acidosis by TRIS buffer failed either to reduce the blood loss or to alter the pathologic lesions. Multiple studies of blood coagulation in the hypercarbic animals revealed no consistent changes when compared with eucarbic animals. In four animals treated with phenoxybenzamine during hypercarbia, blood loss and hemorrhagic gastrointestinal lesions were diminished, suggesting possible pathogenetic role of alpha-adrenergic stimulation. Although the mechanism is not proved, vasoconstriction secondary to adrenergic stimulation may play an important bleeding occurring with hypercarbia.


Alpha1-antitrypsin deficiency with diffuse bronchiectasis and cirrhosis of the liver. The medical literature has emphasized repeatedly the association of alpha1-antitrypsin deficiency with panacinar emphysema and cirrhosis of the liver. Previous reports have linked bronchiectasis with alpha1-antitrypsin deficiency. The present case confirms this association and adds the presence of an hepatic abnormality characteristics of alpha1-antitrypsin deficiency to complete the syndrome. The patient's phenotype was found to be MDuarteZ. It has been suggested that patients with diffuse bronchiectasis should be screened for alpha1-antitrypsin deficiency. We would add that a complete assessment of hepatic function, including liver biopsy, should be carried out in those individuals with reduced levels of alpha1-antitrypsin.


Disruption of proximal aortosaphenous vein anastomosis. Late complication of aortocoronary bypass surgery. A 43-year-old man who had undergone aortocoronary saphenous vein bypass developed disruption of the proximal aorto-saphenous vein anastomosis. Although rare, a mediastinal hematoma secondary to leakage or disruption of an anastomotic site should be considered in patients who develop a mediastinal mass after aortocoronary bypass surgery.


Bypass graft for coronary arterial stenosis following radiation therapy. A 48-year-old man developed symptoms of progressive angina pectoris leading to myocardial infarction 12 years after two large doses of radiation for treatment of superior vena caval syndrome. Angiographic studies showed an isolated critical stenosis in the left anterior descending coronary artery, for which a successful surgical procedure for saphenous vein bypass graft was was performed. Coronary arterial stenosis following radiation therapy has been reported rarely, but this case supports the thesis that such lesion can be treated surgically.


Influence of Steroidal enzyme inducers on the toxicity of pyrogallol, pargyline and nialamide. In rats, the toxic manifestations of overdosage with with parcyline (a monoamine oxidase inhibitor) or pyrogallol (a catechol-o-methyltransferase inhibitor) were diminished by treatment with the more potent steroidal (pregnenolone-16alpha-carbonitrile, spironolactone, etc.) or nonsteroidal (phenobarbital) catatoxic substances. Except for significant protection offered by glucocorticoids (triamcinolene, prednisolone acetate) against pargyline, all other pretreatments (progesterone, estradiol, desoxycorticosterone acetate, etc.) either had no influence on or increase the deleterious effects of the two amine inhibitors. Nialamide intoxication was exacerbated by most of these conditioners.


Acute effects of low doses of clomiphene upon LH release in ovariectomized estrogen-progesterone treated rats. The acute effects of low doses of clomiphene citrate upon serum LH within the first two hours after the intravenous injection into ovariectomized, estrogen-progesterone blocked rats were investigated. There was a short-lasting elevation of LH release 45--60 min after injection of 2.5 microng clomiphene. A second LH releasing effect occurred within 60 min when 50 microng clomiphene or more were injected. Doses between these two dose levels were not effective. It is concluded that these effects may probably be due to a partial reduction of distinct estrogen receptor sites both in the hypothalamus and in the pituitary which causes a short-lasting decrease of the negative feedback of the circulating estrogens.


Interaction of RNA polymerase with promoters from bacteriophage fd. Replicative form DNA of bacteriophage fd, which had been fragmented with the restriction endonuclease II from Hemophilus parainfluenzae (endo R- HpaII), was reacted with Escherichia coli RNA polymerase; the resulting stable preinitiation complexes were analysed using the filter binding assay followed by gel electrophoresis. At 120mM KCL the first-order rate constants for complex decay were determined to be 10(-2)-10(-6)s-1. The second-order rate constants for complex formation were found to be about 10(6) -10(7) M-1 s-1. From these values association constants for the individual promoters were calculated to be 2 x 10(-8) -2 x 10(-11) M-1. The rate of formation and the stability of promoter complexes was enhanced in superhelical DNA. No evidence was found for stable promoter-specific closed complexes consisting of enzyme and helical DNA. This and the kinetic data suggest that the unwinding of base pairs is already important early in promoter selection, and not only for the formation of the final open complex. The initiation of RNA synthesis form the preinitiation complex was faster than complex dissociation and complex formation for all promoters. Consequently, the initiation efficiency of a promoter is determined by the rate of complex formation, and not by its 'affinity' for the enzyme. No correlation was found between the relative order of the fd promoters for the binding and the dissociation reaction. This is explained by different structural determinants, for the two reactions, which are located in different parts of the promoter DNA.


The purification and properties of human alpha1-antitrypsin (alpha1-antiprotease), variant Z. After three stages of preliminary purification, variant Z was chromatographed on a DEAE-cellulose column. Upon elution with a linearly increasing concentration of NaCl, variant Z was recovered in two separate peaks, the first of which contained 81% and the second 19% of the total. The preparation corresponding to the first peak was homogeneous by various criteria. The trypsin and chymotrypsin inhibiting capacities and the specific antigenic activity of the preparation were nearly the same as those of an authentic sample of variant M. Variant Z contained 8 or 9 more gycine residues than variant M, but no appreciable difference was found between their carbohydrate contents. By analytical isoelectrofocusing the isoinhibitors of purified variant Z overlapped with those in the plasma of the donor and were cathodal to, but partially overlapped with purified variant M. After desialysation, the overlap between the different variants became complete, but variant Z contained a larger proportion of cathodal and smaller proportion of anodal components than variant M. Both variants formed five distinct isoinhibitor-protease complexes after incubation with trypsin and chymotrypsin and the corresponding complexes in the different variants completely coincided.


Some observations on the Rohon-Beard cell perikaryon. During the hatching period, the Rohon-Beard cells of Salmo gairdneri showed definite structural maturity of their perikarya, which is in contrast to the amphibian species investigated, where neuronal maturation of the Rohon-Beard cells is finished only in later -- posthatching -- developmental stages.


Somatotopic organization of the eye muscle representation in the semilunar ganglion. A somatotopic arrangement of the extraocular muscle proprioception has been found in the semilunar ganglion. The cells innervating the proprioceptors of the superior rectus and superior oblique muscles lie more dorsally than those innervating the inferior rectus and inferior oblique. The lateral rectus and the medial rectus are represented in the lateral, respectively in the medial portion of the cellular pool which provides the sensitive innervation of the eye muscles.


Inhibition of DNA synthesis in concanavalin A stimulated rat lymph node cells by serum from arthritic rats. Serum from adjuvant arthritic rats inhibits the mitogenic response of rat lymph node cells to concanavalin A, leaving unaffected the response to phytohemagglutinin. This activity is already evident 4 days after adjuvant administration and persists for at least 28 days.


Vitamin C and the immune response.

Vitamin C and the immune response. The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.