Studies on the human testis. VI. NADH-linked reactions of microsomal steroid 20alpha-and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase. NADH-linked 20alpha- and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase activities were demonstrated in the microsomal fraction of the human testis. The microsomal 20alpha-hydroxysteroid dehydrogenase showed substrate affinity to pregnenolone and progesterone and not to 17alpha-hydroxyprogesterone and preferred NADH to NADPH as a hydrogen donor. In the presence of NADH, the optimal pH for the enzyme was 7.7 and the apparent Michaelis constants of the enzyme for progesterone and pregnenolone at 37 C and pH 7.4 were 6.9-7.1 X 10-6M and in the order of 10-5M, respectively, 17alpha, 20beta-Dihydroxypregn-4-en-3-one was the only significant metabolite produced from 17alpha-hydroxyprogesterone by microsomal fraction of the human testis in the presence of NADH. The apparent Michaelis constant of microsomal 20beta-hydroxysteroid dehydrogenase for 17alpha-hydroxyprogesterone in the presence of NADH was in the order of 10-5M at 37 C and pH 7.4. The microsomal 17alpha-hydroxylase catalyzed the metabolism of pregnenolone and progesterone at a similar rate in the presence of NADH. The optimal pH and the apparent Michaelis constant at 37 C and pH 7.4 of the NADH-linked reaction of 17alpha-hydroxylase for progesterone were 7.7 and 5.3-5.4 X 10-7M, resepctively. The NADH-linked enzyme activity for progesterone was competitively inhibited by both pregn-5-ene-3beta, 20alpha-diol (inhibition constant: 1.7 X 10-7M) and 20alpha-hydroxypregn-4-en-3 one (inhibition constant: 6.6 X 10-7M), and was resistant to poor oxygen supply during incubation. The results indicate that the microsomal 20alpha-hydroxysteroid dehydrogenase is a different enzyme from the one in the soluble fraction of the human testis and that microsomal 17alpha-hydroxylase in the human testis is activated by NADH as well as NADPH.


Role of adrenergic stimuli in parathyroid hormone secretion in man. The role of adrenergic stimuli in the secretion of parathyroid hormone (PTH) in man was evaluated. Intradermal injections of isoproterenol, 0.15 mg, or epinephrine, 0.3 mg, caused significant prompt increases in serum PTH levels. These increases were not accompanied by any changes in serum calcium (Ca) during the period of observation. Phenylephrine, 1.5 mg, intradermally, did not cause any significant changes in serum PTH or serum Ca. Propranolol infusion alone significantly inhibited the basal secretion of PTH. This inhibition by propranolol was overcome by isoproterenol administration. The results indicate that 1) beta adrenergic agents increase PTH secretion whereas alpha adrenergic agents have no effect, 2) beta adrenergic stimuli probably play an important physiological role in basal PTH secretion in man.


Action of (1-des(aspartic acid), 8-isoleucine) angiotensin II upon the pressor and steroidogenic activity of angiotensin II. The vascular and steroidogenic responses to (1-Sarcosine, 8-Isoleucine)-, and to (1-Des (Aspartic acid), 8-Isoleucine) angiotensin II were compared in bilaterally nephrectomized, ACTH-suppressed dogs receiving constant infusions of angiotensin II. Aldosterone secretion rate was significantly inhibited by pretreatment with 200 ng/Kg/min of the heptapeptide, (1-Des(Aspartic acid), 8-Isoleucine) ang II, but not by similar doses of the octapeptide, (1-Sarcosine, 8-Isoleucine) ang II. In contrast, the pressor action of ang II was unaffected by (1-Des (Aspartic acid), 8-Isoleucine) ang II though significant inhibition occurred with relatively small doses of (1-Sarcosine, 8-Isoleucine) ang II. This study suggests that: (a) angiotensin receptors in adrenal cortex and vascular smooth muscle are functionally different, and (b) (1-Des(Aspartic acid),8-Isoleucine) angiotensin II is a specific antagonist of steroidogenic effect of ang II.


Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins. Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin.


The effect of an H2-receptor antagonist on food-stimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcers. Comparison with an anticholinergic drug. The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.


Laser fusion of selected dental casting alloys. Laser-fused precious, nonprecious, and mixed metal welds were investigated for optimum weld energy requirement as determined by tensile strength tests. These strengths were compared to soldered unions. Laser fusion is as good as, or better than, unions created by conventional dental joining methods.


Effects of phosphates in acid-containing beverages on tooth erosion. Rat studies demonstrated that low-pH powdered beverage mixes containing monocalcium phosphate caused less molar erosion than reconstituted frozen orange juice and grape juice when these beverages were consumed at excessive levels. A number of sodium phosphate supplements in low-pH beverages were not as effective as monocalcium phosphate in preventing molar erosion. Total acidity or pH values of the beverages could not be used with reliability to predict their potential to cause molar erosion.


Studies of fluorapatite: II. The solubility behavior. The solubility product of fluorapatite has been determined by equilibrating a very pure mineral specimen in KCl solutions at ionic strengths up to 0.1. At pH's less than 5.0 to 6.0 the solubility product of fluorite, and not that of fluorapatite, is the governing principle under the experimental conditions used.


Cellular localization of tyrosine hydroxylase by immunohistochemistry. The enzyme tyrosine hydroxylase (TH) was immunohistochemically localized by the peroxidase-antiperoxidase method in rat to chromaffin cells of the adrenal medulla, large neurons and small darkly staining cells of the superior cervical ganglia and noradrenergic and dopaminergic neurons in brain. As compared with the conjugated peroxidase or immunofluorescence techniques, the peroxidase-antiperoxidase method gave the most selective and specific cytoplasmic localization of TH antisera in every tissue examined. The peroxidase staining with the TH antisera was more intense in dopaminergic than in noradrenergic neurons of the central nervous system. While TH was visualized in cell bodies of both dopaminergic and noradrenergic neurons, it could only be detected in axons and terminals in the dopaminergic system. The perikarya of noradrenergic neurons could be distinguished from dopaminergic neurons by the immunohistochemical demonstration of the enzyme dopamine-beta-hydroxylase only in the former.


Computer-facilitated nutritional analysis. A seven-day dietary analysis of 59 students in the dental health profession indicated that their nutrient consumption was generally adequate. A dental health examination indicated excellent oral hygiene. Nevertheless, many students were deficient in specific nutrient categories. Results suggested that computerized nutritional analysis techniques have general applicability in dental practice and epidemiological testing.


Studies on the specificity of autoantibodies produced in systemic graft-vs-host disease. Anti-erythrocyte antibodies were found in serum and on RBC of F-1 hybrid hamsters afflicted with systemic graft-vs-host (GVH) disease. These antibodies were shown to be reactive with antigenic determinants unique to hamster erythrocytes compared to heterologous erythrocytes and to non-erythrocytic hamster tissues. They fulfilled the criteria for true autoantibodies by failing to discriminate strain specificities among the domestically maintained isogenic hamster lines that were tested. It is suggested that the excessive production of these antibodies results from the allogeneic effect by which donor T-lymphocytes attack host B lymphocytes and stimulate heretofore quiescent self-reactive clones. Moreover,it is proposed that these autoantibodies can function as enhancing antibodies and subvert continued progression of GVH disease. In this regard, they resemble antibodies directed at allogeneic transplantation antigens that have been shown to attenuate and abort GVH processes.


Detection of antibodies to mycobacterium tuberculosis by solid phase radioimmunoassay. The sandwich solid phase radioimmunoassay procedure has been adapted to the serological diagnosis of tuberculosis by the use of disposable plastic haemagglutination trays in which the wells were sensitized with soluble mycobacterial antigen and the subsequent uptake of globulin from test sera detected with radioiodinated antiglobulin. The influence of time and temperature of the incubation stages, pH, washing times, drying and the efficiency of various non-specific blocking agents have been studied. In an initial survey carried out on 319 sera the results obtained showed a good correlation with the presence or absence of established tuberculous infection.


Aryl hydrocarbon (benzo[a]pyrene) hydroxylase: a mixed-function oxygenase in mouse skin. Mouse skin contains aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity which is inducible by aromatic polycyclic hydrocarbons and benzoflavones.  The duration and magnitude of induction, but not the initial kinetics, are dependent on the inducer dose.  The cutaneous hydroxylase activity is inhibited by carbon monoxide and requires the presence of NADPH, indicating that the enzyme is one of the mixed-function oxygenases.  The highest enzyme activity was found in the superficial layer of skin which contains the sebaceous glands and the upper pilary canals.  Enzyme activities were intermediate in the epidermis and lowest in the deeper dermal layers.


Role of urease in pyelonephritis resulting from urinary tract infection with Proteus. The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.


Kinetics of hemodiafiltration. II. Clinical characterization of a new blood cleansing modality. Hemodiafiltration, a process in which whole blood is first diluted with a physiologic electrolyte solution and then ultrafiltered across a membrane to convectively remove solutes and excess water, has been applied clinically for the first time. Six-hour hemodiafiltration with a 1.6 m.2 hollow-fiber ultrafilter was applied intermittently to an anephric patient as an alternative to 6-hour hemodialysis using a 1.45 m.2 coli. A quantitative basis for evaluating clinical hemodiafiltration kinetics was developed, and the results were compared with data from prototype devices. With blood, diluting fluid, and ultrafiltrate flow rates of 200 ml. per minute, removal rates of urea and creatinine by both hemodiafiltration and dialysis were comparable, but for solutes of larger molecular weight (uric acid, phosphate, and inulin) removal rate was significantly greater for hemodiafiltration. The observed ultrafiltrate flux was similar to values predicted from in vitro studies. With the present membrane formulation the measured sieving coefficients for inulin, creatinine, and urea were not significantly different from one, and whole blood clearances for these solutes were 117, 108, and 101 ml. per minute, respectively. This solute clearance pattern is very similar to the human kidney and in sharp contrast to standard coil hemodialysis.


Alteration of factor VII activity by activated Fletcher factor (a plasma kallikrein): a potential link between the intrinsic and extrinsic blood-clotting systems. Although surface contact is known to accelerate the one-stage prothrombin time of human plasma through the participation of Hageman factor (factor XII) and factor VII, it has not been clear whether Hageman factor interacts with factor VII directly or indirectly. Recently, Gjønnaess reported experiments suggesting that plasma kallikrein was an intermediate between Hageman factor and factor VII. The present study was undertaken to elucidate the interaction of plasma kallikrein and factor VII. Incubation of Fletcher-trait plasma (deficient in a plasma prekallikrein) with kaolin at 0 degrees C. did not induce shortening of the Thrombotest time or enhancement of factor VII activity, in contrast to studies of normal plasma. Monospecific rabbit antiserum against plasma kallikrein blocked the shortening of the Thrombotest time of normal plasma brought about by kaolin. Purified Hageman factor fragments (prekallikrein activator) induced an increase in factor VII activity in normal or Hageman-trait plasma, but not in Fletcher-trait plasma. A purified plasma kallikrein preparation enhanced factor VII activity in all plasmas, including that of Fletcher-trait plasma. The effect of the kallikrein preparation was blocked by soybean trypsin inhibitor, Trasylol, or rabbit antiserum against kallikrein, but not by lima bean trypsin inhibitor or antiserum against Hageman factor. The activity of partially purified factor VII was enhanced by purified kallikrein in the presence, but not in the absence of factor VII-deficient plasma. These results further support the idea that the enhancement of factor VII activity by surface contact is via Hageman factor and plasma kallikrein, suggesting a possible link between the intrinsic and extrinsic pathway of blood clotting. The significance of this phenomenon in hemostasis in vivo remains to be elucidated.


The effect of pH on radioimmunoassay of LH and FSH. Freezing and thawing of human serum produces alkaline changes in the pH. Weak buffers were of insufficient capacity to compensate for these pH changes. Thus the effect of serum pH on modified solid-phase and double-antibody radioimmunoassay (RIA) of LH and FSH was studied. Pooled postmenopausal serum standardized against the Second International Reference Preparation of Human Menopausal Urinary Gonadotropon was used as a laboratory standard. In the solid phase RIA for LH and FSH, slopes with the greatest maximum binding were obtained at pH 6.4, whereas for the double-antibody method best results were obtained at pH 8.0. Since there is individual variation in the pH of various serum samples, different values will be obtained from samples containing the same amount of hormone. It is sum samples be standardized by the use of buffers with the capacity to keep the pH of the serum constant and that serum standards be dialyzed.


Serum levels and biochemical characterization of oestradiol-17 beta dehydrogenase in umbilical cord blood. The properties of the enzyme oestradiol-17 beta dehydrogenase from human umbilical cord serum have beem compared with those of oestradiol-17 beta dehydrogenase present in the maternal peripheral blood. On the basis of studies on stability, specificity, optimum pH, rate of enzymic reaction and Km determinations it can be concluded that oestradiol-17 beta dehydrogenase in the umbilical cord arteries has an activity between 5 and 15 times higher than in the umbilical cord vein and about 65% of the activity of the enzyme present in the maternal peripheral blood. The present results strongly suggest that in pregnancy the enzyme oestradiol-17 beta dehydrogenase is elaborated not only by the placenta but also by the foetus.


Effects of hypothalamic extracts, neurotransmitters and synthetic hypothalamic releasing hormones on adenylyl cyclase activity in the lobes of the pituitary of the dogfish (Scyliorhinus canicula L.). Neutralized acid extracts of the median eminence of the dogfish hypothalamus were found to cause a dose-related activation of adenylyl cyclase in all lobes of the dogfish pituitary. Equal concentrations of extracts of extrahypothalamic areas of the dogfish brain did not activate the enzyme. The putative neurotransmitters melatonin, serotonin, adrenaline, noradrenaline, dopamine and acetylcholine were without effect, as were the prostaglandins E1 and E2. The effects of synthetic mammalian hypothalamic hormones were also studied. Both thyrotrophin releasing hormone and gonadotrophin releasing hormone activated the ventral lobe enzyme, but had no effect on the adenylyl cyclase of the other three lobes. The tripeptide, Pro-Leu-Gly-NH2, a possible melanocyte-stimulating hormone release-inhibiting factor had no effect on the enzyme of the neurointermediate lobe. It is suggested that all four lobes of the dogfish pituitary may be under hypothalamic control and that this control is likely to be mediated by peptide hormones, as in mammals.


Binding of human chorionic gonadotrophin by rat testis: effect of sexual maturation, cryptorchidism and hypophysectomy. The specific binding of 125I-labelled human chorionic gonadotrophin (HCG) by rat testicular homogenate as compared with isolated Leydig cells differs with respect to total binding capacity but not to the dissociation constant (Kd) as revealed by Scatchard analysis. The maximal binding capacity for [125I]HCG of crude testicular homogenate was 95 ng/g rat testis. Hypophysectomy causes a decline in binding capacity within the first three days but on the 20th and 30th day after hypophysectomy the relative binding capacity no longer differs from that of controls. Binding capacity is enhanced in cryptorchid testes relative to normal, and increases during sexual maturation to a peak shortly before puberty.


Influence of dietary protein restriction on immune competence. I. Effect on the capacity of cells from various lymphoid organs to induce graft-vs.-host reactions. The effect of dietary protein restriction in mice on the capacity of their lymphoid cells to induce graft-vs.-host responses (GVHR) was studied. Mice were fed diets containing 4% or 20% protein ad libitum. The GVHR capacity of cells from all lymphoid organs of deprived mice was increased on a cell-for-cell basis over that of their normally fed counterparts. The slope of the dose-response curves did not change for spleen and mesenteric lymph node cells although their reactivity was increased by fourfold, and 50% respectively. The slope of the curves for thymus and Peyer's patches was changed indicating fundamental changes in the reactive cellular populations of these organs. Changes in GVH reactivity of cell populations from deprived mice were not mediated by increased corticosteroid production as adrenalectomy did not reduce their GVH responses. An explanation for the results was sought in a general decrease in production of short-lived cells with a rapid turnover such as most B cells. Long-lived T cells appear to persist and retain their reactivity for quite long periods in the face of nutritional insults.


Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes. A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.


Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex. A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.


Psychiatric screening of civil service candidates with particular reference to police applicants. This prelimary report has reviewed the activities of a Medical Review Board for a Civil Service Commission. The responsibility of the Board is to review conflicting data in cases where the hiring authority has attempted to exclude a candidate, particularly a police candidate, on the grounds that the applicant is mentally unfit to perform the duties of the position. This rule has been applied primarily to police applicants, secondarily to fireman applicants, and rarely to other. Psychiatrists who participate must be aware of the underlying conflicts within civil service systems, the possibility of manipulation, and the rigidity of the system which is designed to protect the greatest number. Civil service systems have limited discretion on personnel policies. Therefore, psychiatrists must be careful not to act as arbiters for social institutions without a sound and meticulous basis for their participation. For those psychiatrists who participate in the process, the urgent need to do so in accord with professional standards is stressed, recognizing that standards change and that the nature of participation will be scrutinized by many in society outside the profession.


Identification of flurazepam (Dalmane) and a primary metabolite in urine by thin-layer chromatography. A relatively simple, routine method has been described for the qualitative identification of flurazepam and its primary metabolite 7-chloro-1-(2-hydroxyethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in urine. We have described two extractions and several identification procedures by which flurazepam and its primary urinary metabolite can be identified by TLC.


Squid retinochrome.

Squid retinochrome. Retinochrome is a photosensitive pigment located primarily in the inner portions of the visual cells of cephalopods. Its absorption spectrum resembles that of rhodopsin, but its chromophore is all-trans retinal, which light isomerizes to 11-cis, the reverse of the situation in rhodopsin. The 11-cis photoproduct of retinochrome slowly reverts to retinochrome in the dark. The chromophoric site of retinochrome is more reactive than that of most visual pigments: (a) Hydroxylamine converts retinochrome in the dark to all-trans retinal oxime + retinochrome opsin. (by Sodium borohydride reduces it to N-retinyl opsin. (c) Lambda max of retinochrome shifts from 500 to 515 nm as the pH is raised from 6 to 10, with a loss of absorption above pH 8; meanwhile above this PH a second band appears at shorter wavelengths with lambda max 375 nm. These changes are reversible. (d) If retinochrome is incubated with all-trans 3-dehydroretinal (retinal2) in the dark, some 3-dehydroretinochrome (retinochrome2, lambda max about 515 nm) is formed. Conversely, when retinochrome2, made by adding all-trans retinal2 to bleached retinochrome or retinochrome opsin, is incubated in the dark with all-trans retinal some of it is converted to retinochrome. Retinal and 3-dehydroretinal therefore can replace each other as chromophores in the dark.


Minor tranquilizers in the treatment of aggression. Clinical trials designed to evaluate the efficacy of drugs in human aggression have been scarce until recent years. The potential antiaggressive action of minor tranquilizers in humans has received little attention in spite of the claimed "taming effect" in some animal studies. A recent report examining the literature regarding the effects of benzodiazepines on animal models of aggressive behavior has pointed out the lack of consistency in such findings. Similar observations have been noted in humans where reduction in aggressive manifestations is contrasted with an increase in hostility in a few studies, as well as with the appearance of "paradoxical" rage reactions. Some variables that could account for such discrepancies have been advanced. They include, among others, dosage, acute vs. chronic drug administration, and possible qualitive differences among this group of agents. Individual variations as to presenting clinical picture, initial levels of anxiety and hostility, and personality types have also been mentioned. Implications of some of these findings for future clinical research are discussed. At present, a study designed to test the efficacy of two benzodiazepines, at dosages higher than those usually recommended, is being carried out in a population of anxious, aggressive-prone individuals with poor impulse control. Thus far, and in agreement with our previous clinical experience, we have not seen "paradoxical" rage and such high dosages have been well tolerated.


Conceptual issues in the use of drugs for the treatment of aggression in man. Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded.


Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs. Most of the drugs used in the treatment of aggressive syndromes have originally been developed for other clinical applications. Despite significant differences in the pathogenesis of various aggressive disorders, the frequently used "antiaggression" drugs are the major tranquilizers (neuroleptics). If the aggresstion is associated with psychosis, chlorpromazine or haloperidol are the drugs of choice. Aggressive disorders within the acute and chronic brain syndromes are best treated with pericyazine, thioridazine, and thiothixene. In aggressive symptoms of mentally retarded patients, particularly with epileptic syndromes, a new benzazepine (SCH12,679)was found to be very effective. Aggression associated with alcoholism or narcotic addiction showed best response to chlorpormazine and haloperidol. As a general rule, in aggressive patients with clinically known epilepsy, or with abnormal electroencephalographic findings, the major tranquilizers with potent sedative properties should be given with great caution.


Abnormal intrafusal muscle fibres in myotonic dystrophy: a study using serial sections. Studies of the extent and complexity of intrafusal muscle fibre splitting in myotonic dystrophy have been carried out in three spindles obtained at muscle biopsy, and in nine spindles found in the lumbrical muscle of a case that came to necropsy. It is suggested that splitting, due to mechanical stresses, leads to a regenerative response in the separated fragments.


Lipid storage myopathy with normal carnitine levels. A 28-year-old female, who showed a floppy baby syndrome during early infancy, had a non-progressive proximal muscle weakness with easy fatiguability since childhood. Two muscle specimens biopsied at the age of 28 years revealed myriads of 1-3-mum wide abnormal spaces containing neutral fat in type I and type II fibers.  Both biopsies demonstrated a type I fiber preponderance.  Electron microscopy demonstrated lipid excess and normal mitochondria by simple inspection. The mitochondrial area and sarcotubular membrane profile concentration in morphometry of longitudinal sections were also normal.  Cross-sections, however, revealed a slight decrease of the individual mitochondrial size and of the sarcotubular membrane profile concentration . Serum and muscle carnitine levels and the muscle carnitine palmityltransferase level were all within normal range.  Besides carnitine deficiency other biochemical defects can occur in lipid storage myopathy, which represents a syndrome rather than a unique disease entity.


Tardive dyskinesia treated with pimozide. We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines. Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage (mean 18.8 mg/day) for 6 weeks. There was no deterioration in the therapeutic action of pimozide over this time. Parkinsonism and sedation were the main adverse effects. They were corrected by reduction of the dose of pimozide, but often recurred so that further adjustments of dosage were necessary. Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased.


A follow-up study of surgically treated cryptorchid patients. A group of 112 adult patients were traced who had had childhood orchiopexies at an average age of 9 yr at two childrens' hospitals. Sixty-seven per cent of all married patients had sired children although only 44% of the married bilateral cryptorchid patients had done so. The percentage paternity of the unilaterally cryptorchid patients was normal when compared with the general population. There appeared to be no difference in the eventual results of the two types of orchiopexy performed on this series of patients.


Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations. Electron microscopic and morphometric investigations on undescended testicles show a decreased volume density of the spermatogonia up to the age of 5 (approximately 60%, p smaller than 0.005), corresponding to investigations by light microscopy. There are no ultrastructural differences in the seminiferous tubules between normal and undescended testicles up to the age of 1 yr. There are ultrastructural changes of Leydig cells within the first year of life. Based on these investigations, we conclude that the optimal time for surgical intervention in case of undescended testes is in the second year.


Plasma gonadotropins and androgens in surgically treated cryptorchid patients. Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases.


The effect of cigarette smoking on anaerobiosis in the oral cavity. Nineteen young adult male smokers were compared to 19 adult male nonsmokers to determine if cigarette smoking resulted in any changes to anaerobic bacteria in dental plaque, to intraoral oxidation-reduction potential (Eh) levels, or to intraoral pH. There was no statistical difference between smokers and nonsmokers in the proportion of anaerobic bacteria found in dental plaque. There were no significant differences between smokers and nonsmokers with respect to the resting Eh in the floor of the mouth nor in the Eh in the region of buccal surface of the upper molars. The smoking of one cigarette resulted in a dramatic fall in Eh in both intraoral regions and this occurred in all subjects, both smokers and nonsmokers. The magnitude of this fall in Eh was similar in both groups. There were also uniform increases in pH, but these pH changes were much smaller in magnitude.


Role of the cell membrane in the uptake of 3H-actinomycin D by mammalian cells in vitro. The characteristics of the uptake of 3H-Actinomycin D (3H-AMD) by mammalian cells was studied in vitro.  Chang liver (CH) cells accululated 3H-AMD over 100 times above extracellular levels.  CH cells accumulated and released 3H-AMD at a slow rate.  Treatment of cells with ethanol-acetone or Tween 80 significantly increased the rates of drug uptake and release by cells, indicating that the cell membrane effectively slows down passage of 3H-AMD in and out of cells.  Cellular 3H-AMD uptake is temperature dependent and not energy dependent.  The rates of 3H-AMD uptake after short and prolonged incubation suggest that AMD entry into cells consists of two phases, an initial phase of rate-limiting diffusion process followed by a second phase of binding to deoxyribonucleic acid.  Although lymphocytes take up less 3H-AMD than CH cells, the differential inhibitory effect of AMD on nucleic acid synthesis in the two cell types is small.  The time required for cells to be fully saturated with 3H-AMD varies with the cell type and is based on permeability differences of the cell membrane for 3H-AMD.  The time required for lymphocytes and CH cells to be fully saturated with 3H-AMD is reflected in the differential effect of the drug on nucleic acid synthesis.  The physiological basis of AMD resistance can be explained on the basis of impaired diffusion of the drug into cells.


Stereospecific blockage of the alpha adrenergic receptor by substituted 1-aminotetralines. Certain members of a series of 1-aminotetraline derivatives reversed the epinephrine pressor response in dogs; this effect occurred with the R- but not the S-isomers.  Studies with rabbit aortic strips indicated competitive blockade of the alpha adrenergic receptor by the active agents.  Receptor protection experiments supported the interpretation that this disruption of receptor function was due to occupancy blockade.  This led to a hypothesis defining the steric properties of the alpha receptor and the active conformation of epinephrine at this receptor.  However, two hydroxy substituted 1-aminotetralines ans two trihydroxytetrahydrosioquinoline derivatives, which were investigated to support this hypothesis, failed to show the predicted alpha adrenergic agonist activity.  It is concluded that the interaction of certain 1-aminotetralines with a stereospecific binding site at the alpha receptor mimics occupancy blockade.  However, this binding site is probably not entirely identical with the epinephrine binding site at the alpha receptor.  Furthermore, the cyclic tetrahydroisoquinoline derivatives do not represent the active conformation of epinephrine at the receptor.


An analysis of the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ). The pithed rat preparation has been used to study the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ).  In this preparation, an increase in blood pressure is indicative of alpha stimulation, and an increase in heart rate is indicative of beta stimulation.  Using this preparation, we have found that TIQ is approximately 3 orders of magnitude less potent than norepinephrine in evoking changes in blood pressure and heart rate.  The activity of TIQ has also been studied in pithed animals which had been previously sympathectomized with 6-hydroxydopamine.  Sympathectomy produced a marked reduction in cardiac norepinephrine, and it nearly abolished vascular responses to injected tyramine.  Following sympathectomy, pithed animals were supersensitive to norepinephrine and subsensitive to TIQ. Similar results were obtained on pithed animals that had been pretreated with cocaine.  It is concluded that TIQ is a weak sympathomimetic agent possessing both directly and indirectly acting properties.  The data are discussed in terms of a proposal that TIQ may be a false adrenergic transmitter.


Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase. Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His).  Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner.  The metabolism of C-His was more affected than that of R-His.  The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid.  Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver.  After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls.  The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs.  After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues.  The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.


Growth of Nosema algerae in pig kidney cell cultures. Nosema algerae, a microsporidan parasite of mosquitoes, can infect pig kidney cell cultures.  Sores germinated in the culture medium, infected the cells within 30 min of germination, multiplied, and produced spores.  The early developmental stages in the N. algerae life cycle are discribed.


Nitrofuran-reducing enzymes of Euglena.

Nitrofuran-reducing enzymes of Euglena. Euglena gracilis strain Z, green, dark-brown, and "bleached" with N-methyl-N-nitro-N-nitrosoguanidine, was found to contain 2 soluble enzymes which reduce nitrofurans.  A small amount of activity was demonstrated also in a particulate fraction of sonic extracts, but none in isolated chloroplasts.  The reduction of 5 nitrofurans, having widely differing bleaching activities, by each of the 2 enzymes was examined.


Effect of initial freezing temperature, addition of glycerol and dilution on the survival and fertilizing ability of deep-frozen ram semen. The influence oftemperature, addition of glycerol, initial freezing temperature, method of dilution, level of glycerol in the diluted semen, equilibration time and type of diluent on the survival and fertilizing capacity of deep-frozen according to the best conditions was compared with that of "fresh" semen. The addition of glycerol at plus30 degrees C resulted in a highly significant decrease in the mean proportion of motile spermatozoa immediately after thawing compared with the effect of addition at plus 4 degrees C. The immersion of the straws at minus55 degrees C significantly reduced the revival of the spermatozoa compared with initial freezing at lower temperatures. The exposure time to glycerol had no significant effect on the survival of spermatozoa after thawing and incubation, but fertility was significantly higher with 4% than with 2% glycerol. The I. N. R. A. diluent provided better sperm survival and a significantly higher conception rate than did lactose-egg yolk extender. The semen frozen according to the best conditions (about 50% of the samples) had a fertilizing ability similar to that of "fresh" semen when the proportion of motile spermatozoa before, and after 1 or 3 hr of incubation was equal to or above 45, 40 and 30% respectively.


Maternal immunization to paternal antigens in multiparous mice. Mice of the CBA strain which had given birth to five litters sired by males of a different H-2 type (C57BL/10) showed evidence of immunization to paternal antigens, in that the numbers of lymphocytes forming alloclusters with paternal erythrocytes were significantly elevated. On the other hand, the graft-versus-host responsiveness of maternal splenic lymphocytes to paternal antigens remained virtually unchanged, showing only a slight increase at Day 8 of the assay.


Brain monoamine levels in the cow during oestrus and metoestrus. Norepinephrine, dopamine, and serotonin concentrations in the hypothalamus and stalk-median eminence were estimated in nine Hereford heifers at the onset of oestrus or 48 hr later. Significant differences in levels of monoamines at these stages of the oestrous cycle were not evident. Norepinephrine levels were similar in the hypothalamus and the stalk-median eminence, but dopamine and serotonin concentrations were significantly higher in the stalk-median eminence.


Treatment of circulatory shock. Use of sympathomimetic and related vasoactive agents. Reduction of effective blood flow represents the primary disturbance accounting for circulatory shock. Four categories of circulatory shock are identified: cardiogenic, hypovolemic, distributive, and obstructive. The pharmacology and clinical implications for treatment of shock with vasoactive drugs are reviewed in this context. Except for epinephrine, when it is used for treatment of anaphylactic shock, there is no specific indication for the routine use of alpha- or beta-adrenergic receptor agonists. These agents may increase blood pressure or cardiac output, but nutritive flow is not necessarily improved. Comparable limitations are observed with alpha-adrenergic receptor blocking agents. However, selective effects on the myocardium and on the resistance, exchange, and capacitance vessels may be advantageous as an interim and complementary measure. Since vasoactive drugs frequently intensify the fundamental defect accounting for perfusion failure, their selective rather than routine employment is mandatory.


Diplococcus pneumoniae. Cellulitis in drug addicts. Cellulitis caused by Diplococcus pneumoniae was diagnosed in two heroin users. To our knowledge, this medical emergency, clinically indistinguishable from deep fasciitis of pyomyositis, has not previously been reported as having been caused by the agent identified in these two patients.


[Comparative evaluation of new drugs used in the treatment of cardiac arrhythmia]. The paper summarizes the experience gained in treating 830 patients with various cardiac rhythm disorders by employing new antirhythmic agents (propranolol, practolol, pindolol, alprenolol, oxyprenolol, benzoral, verapamil, lidocaine, imaline, sparteine, pulsonorma, disopyramide and quinidine durules). Comparative data on the efficacy of these agents are presented and indications and counterindications for their use are discussed.


[Electroimpulse therapy of auricular fibrillation]. Data derived from clinical, electro- and polycardiographic observations of 68 patients subjected to electric stimulation therapy are presented. The evaluation of late results of the treatment showed that clinical factors such as the patients' age, the nature of the affection, the degree of cardiac insufficiency, the standing of auricular fibrillation are not decisive in determining indications and contraindication for electric stimulation therapy. A considerable worsening of the cardiac dynamics with developing fibrillation arrhythmia, especially in patients suffering from cardiosclerosis, and a distinct improvement of the polycardiographic indices after defibrillation point to the need of attempting, whenever this is possible, to bar the auricular fibrillation. A pretreatment with potassium preparations and lengthy maintenance therapy with quinidine or quinidine-like agents is recommended. An analysis of the ECG findings after the electric stimulation therapy (heart rate, and its regularity, the state of the intraatrial and atrioventricular conduction) enable it to foresee the retention time of the re-established rhythm.


Cationic proteins of human granulocytes. IV. Esterase activity. The purfied antibacterial cationic proteins 1 to 7 (component 1 being the most cationic) of human neutrophil granulocytes have been assayed for enzyme activities. Components 1 to 4 and component 7 exhibited activities on tyrosine esters indicating a chymotrypsin-like activity with a neutral pH optimum. The inhibition of the esterase activity by diisopropyl fluorophosphate and phenylmethyl sulfonylfuoride also indicated the similarity to chymotrypsin, with a serine residue in the active center. In addition, the cationic proteins attacked complex substrates like casein and fibrinogen, suggesting a true proteolytic activity. Since the esterase activity of these proteins is heat-labile but the antibacterial activity against Staphylococcus aureus is heat-stable, it is concluded that the chymotrypsin-like activity is not essential for the microbicidal activity. There is evidence to suggest that the cationic proteins of human granulocytes are present in the cytoplasmic granules and exhibit antibacterial activity after release to the phagocytic vacuole and that, after extrusion from the cell, the proteins might be involved in the mediation of the inflammatory process due to enzyme and cationic activities.


Variable-column bubble oxygenator. A new system for bubble oxygenation. A new bubble oxygenator has been developed. Its main advantage is that the dimensions of the oxygenating chamber can be varied. Thus, the capacity for oxygenation may be adapted to different patients. It was used in 2,700 open-heart operations performed at the Institut do Coracão, Faculdade de Medicina, Universidade de São Paulo, between January, 1971, and December, 1973. A group of 50 patients were subjected to more detailed studies. We found that the average hemolysis was 38.67 mg. per cent with a mean perfusion duration of 69 minutes, 38 seconds. Fibrinogen and platelet concentrations decreased by 14 and 25 per cent, respectively. The pH, PcO2, PO2, and base excess before and after cardiopulmonary bypass ranged within normal levels, and oxygenation (PO2) was always satisfactory.


[Burns combined with mechanical trauma]. On the basis of several years' material the mechanical lesions combined with burns are analysed by the authors and the diagnostical and therapeutical problems are dealt with. On the basis of their experiences it is pointed out that in the case of primary surgical management the reciprocal aggravating effect does not develop. Even in second-degree burned area primary healing of the suture following the wound excision has been observed. Extension treatment of the fracture is but rarely successful, the ideal method is the stable osteosynthesis.


[Primary management of injuries to the lateral ligament of the knee joint]. A long-used method: the primary suture of the lesions of the collateral ligaments of the knee joint is discussed by the authors. Because of the unsatisfactory results this method did not become a routine procedure. On the basis of their 24 cases the method is recommended by the authors. Atraumatic operative technique and the importance of the post-operative treatment are emphasized by the authors.


[Injuries of the cervical spine].

[Injuries of the cervical spine]. In connection with 44 patients, who suffered injuries of the cervical spine, the types of the fracture and dislocation of the cervical spine are discussed. The injuries of the cervical spine--with or without injury of the spinal marrow--signify hard tast in respect of therapy. The conservative (extension) treatment of surgical intervention are even nowadays much debated themes in the neurosurgery. The introduction of Crutchfield tongs was a definite advance in the latter years. With this treatment method the restitution of the form, continuity and stability of the cervical spine is possible. In the opinion of the authors, surgical intervention (laminectomy) is necessary only in the case of progressive symptoms of compression of the cervival marrow (liquorstop). The survival of the patients depends often on the quick and proper treatment. The prevention of complications and the quick elimination are of great importance. Safeguarding of the physical and psychical conditions of the patients is the essential requirement of their rehabilitation after injuries of the cervical spine.


[Avascular necrosis of the humeral head]. On the basis of observed cases the avascular necrosis of the head of the upper arm is discussed. After the lesion occurred on the proximal end of the humerus this late complication is not to be excluded. Besides the roentgenological signs, in the authors' opinion, the "free interval" in the patients' complaints may be of the greatest importance. The disturbance of the blood supply of the fractured piece of the upper arm may be responsible for the protracted recovery, in certain cases even for the lasting limitation of motion. No surgical treatment has been performed in the authors' cases.


[Congenital shoulder dysplasia and luxation]. In connection with the demonstration of their cases the congenital dysplasia and luxation of the shoulder are discussed. The theories in respect of the pathogenesis of this rare clinical picture, the differential diagnosis as well as the therapeutical possibilities are resumed.


[Substitution of the tendon sheath by autologous vein in the "no-man's land" of the hand]. Reconstructive surgical interventions on the level of the proximal phalanges and performed after the lesions of the flexor tendons on the distal palm are discussed. In order to reduce the adhesions "bridging of the no man's land" by means of an autotransplanted vein is recommended by the authors. The vein-graft cannulated on a silicone bar is embedded within a few weeks, and after the removal of the silicone the "no man's land" is "over-bridged" by a pseudotendon sheath, stuffed with endothelium of good sliding surface. Thus, in the second sitting each of the plastic "bridge" methods (Bunnell, Paneva--Holevitch) may be performed. The operative technique and the first 4 cases are shortly discussed by the authors.


[Ultrastructural changes in human skeletal muscles following tendon and nerve injuries. I. Ultrastructural changes following tendon injuries]. During reconstructive procedures performed 4-16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrium could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: these were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathologic changes have been observed in the sarcolemma, the cell nuclei and the motor nerve end-organs.


[Treatment of sternum fractures].

[Treatment of sternum fractures]. The frequency and the treatment of the sternal fractures is discussed by the authors. 5 patients with sternal fractures have been treated by the authors, and 3 of them were operated on. In one patient early operation has been performed, and in another the osteosynthesis of the sternum has been carried out 3 years after the lesion. In the 3d patient the bone piece broken down from the sternum damaged the arteria mammaria int. sin., necessitating thus surgical intervention.


[Unusual self mutilation with the purpose of obtaining illegal insurance benefits]. In this unusual form of self mutilation the fracture of the phalanx has been carried out--upon request--by foreign person (inderect self mutilation), in order to obtain illegal accident insurance money. Short survey of the relevant literature is given and the possibilities are outlined, which facilitate at the primary wound dressing the establishment of suspicious cases.


[Total luxation of the ankle, without fracture]. In the 4 and 10 years' material of two Surgical Departments four total luxations of the talus--without fracture--have been observed by the authors. This luxation is a very rare lesion. The authors' cases are described in detail. All patients heald without complications. The Hungarian and foreign literature dealing with isolated talus luxation is reviewed in detail. The biomechanics, the problems of diagnosis and the treatment are discussed.


Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators. The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes.


Late failure or human renal transplants. An analysis of transplant disease and graft failure among 125 recipients surviving for one to eight years. The purpose of the present paper was to study clinical, morphological and immunological aspects of late rejection of renal allotransplants. We have, therefore, analyzed the occurrence and nature of renal transplant disease and graft failure among 125 recipients surviving for 1 to more than 8 years after transplantation. In this population transplant disease as defined by the appearance of heavy proteinuria and/or steadily declining graft function occurred in 22 patients. At the closure date of the study on December 31, 1972 complete graft failure had occurred in 12 of these 22 patients and 4 of these have died. In addition two patients died in the presence of normal graft function, due to chronic hepatitis and metastatic cancer respectively. As based on clinical findings, pathophysiological features and renal lesions the patients with late transplant disease were classified into two groups and described accordingly. Group A, termed glomerular transplant disease, included a majority of 16 patients, constituting a rather homogenous idsease entity in relation to course of disease, clinical findings and renal lesions as studied by light-, immunofluorescence- and electron microscopy. All these patients presented with heavy proteinuria, which was non-selective in all but two, resulting eventually in complete loss of graft function in eight cases. All these patients developed hypoalbuminemia and hypercholesterolemia, and one half manifested a classical nephrotic syndrome. Arterial hypertension occurred in all patients except two. Glomerular structure as studied by light microscopy revealed a number of lesions of a rather polymorphous pattern in all patients in group A. Endomesangial proliferation, hyperplasia and segmental proliferation of epithelial cells and thickening of capillary walls were prominent features, although the degree of severity, extension and type of lesion occurred in such varying proportions that classification into any well characterized category of glomerulonephritis was not possible. All cases in group A revealed immune deposits, most frequently containing IgG, IgM, complement and fibrinogen. IgA, IgD and IgE were also demonstrated in a lesser proportion of cases in this group. The immunofluorescent pattern was a mixed granular and linear, and in no case strictly linear or granular alone. The ultrastructural investigation contains a detailed analysis of the


[The significance of histochemical demonstration of oxidative enzymes in the interpretation of local and remote effects of experimental brain lesions]. In cortex, habenular- or hypothalamic regions of white rats electrocoagulation was carried out. Animals were killed from 6 days to 5 months after the operation. Serial slides of the brain were investigated by the aid of a reaction of SDH, alfa-GPDH, LDH, G6PDH, TPND. Group of neurons around the lesion may show a decreased, normal and increased activity of the enzymes investigated. As for the far effect of the lesion in case of the injury of the postcomissural fornix changes could have to be revealed in the corpus mamillare. Activization of neuroglia is marked by the increase of the reaction of G6PDH, LDH and TPNDH. Enzyme activity of cells of microglial origin at the beginning seems to be significant, later on, when the activity of phagocytes comes to the end it decreases to the minimum. Regeneration of cells of the leptomeninges and their role in demarcation of the process is marked by the increase of enzyme activity.


[Diagnosis of pancreatic function by the selenomethionine--75Se test]. Dterminations of 75selenium radioactivity and pancreatic enzyme in duodenal aspirate were carried out in 50 patients after i. v. injection of selenomethionine-75Se.  After standardized excitation of the pancreas with pancreozymin-secretin, a significant correlation (r = 0.654) between excreted 75Se radioactivity and trypsin production could be established.  The test is suitable for the recording of exocrine pancreas function while avoiding expensive enzymatic methods.  The combined use of pancreas scintigraphy--using the double radionuclide substraction technique-with the radioselenomethionine test (RSMT) provides comprehensive diagnostic information on the morphology and function of the pancreas.


Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae. Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for on a minimal medium.


Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue. Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation. Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes. It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation. During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone. The possible long-term deleterious effects of these agents for man even now remain to be determined. Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity. One apparently non-mutagenic thioxanthenone has been found. A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other.


Evaluation of patient-care protocol use by various providers. A symptom-oriented protocol for acute pharyngitis was evaluated in a busy general medical clinic staffed by physicians and graduate and student physician's assistants. We observed significantly improved performance by all providers in collection of medical data, utilization of laboratory tests,and appropriate use of antibiotics after introduction of the protocol. Patient charges were less when the protocol was used, but these savings were offset partially by the cost of audit. Compliance with and acceptance of the protocol differed among the various health providers, with physicians demonstrating significantly lower levels than nonphysicians. Patient-care protocols provide an effective means of monitoring the process of medical care, detecting weakness in supportive clinic services, and affording educational feedback for all health providers.


Use of an angiotensin II antagonist (saralasin) in the recognition of "angiotensinogenic" hypertension;. The possibility has been explored of using a specific angiotensin ii antagonist, saralasin (P-113, 1-sar-8-ala-angiotensin ii) to recognize patients whose hypertension depends upon excessive angiotensin ii activity.  Among 60 hypertensive patients, saralasin infusion reduced blood pressure in 16 "responders," but not in 44 "nonresponders." The "responders" had the following findings: elevated plasma renin activity in renal vein (or veins) or peripheral veins or both (16 of 16); reduced renal blood flow, shown by arteriography, isotopic studies or pyelography (15 or 16), or progressive azotemia (one of 16); and reduction in blood. These findings indicated that angiotensin ii probably caused hypertension in the "responders," One "nonresponder" had renal vein levels of plasma renin activity suggestive of angiotensinogenic hypertension.  Since hypertension was invariably angiotensinogenic when it was reduced by saralasin and, with one possible exception, was never angiotensinogenic in "nonresponders," the antagonist appears to provide an efpressure to or toward normal after corrective operation (four of four) or propranolol therapy (eight of eight). fective means of recognizing angiotensinogenic hypertension.


Medical education in China in the postcultural Revolution era. The Cultural Revolution has had an important impact on Chinese medical education. The Chinese system is engaged in a vigorous program to solve health-manpower needs in the rural areas by emphasizing de-professionalization, mass orientation and accountability to the community. Among the notable changes within the medical schools are the following: an admission process favoring the recruitment of peasants, factory workers, and the military; a three-year program with heavy emphasis on practicing in rural communities; widespread integration of the traditional Chinese and Western systems of medical practice; and manual labor and political seminars, which compose more than 25 per cent of the required curriculum. These innovations have been greatly facilitated by a strong national commitment and supportive political system. The fact that less than 10 per cent of doctors in China today are graduates of college-level medical education indicates the importance of other entry possibilities.


Studies on the synthesis and subcellular distribution of dopamine in the rat adrenal medulla. Rats received intravenous injections of 3H-tyrosine and were killed at various time intervals thereafter. 3H-dopamine (DA) in the adrenals reached a maximum within 1.5 min after the administration of 3h=tyrosine. From the 15th min it disappeared with an apparent half life of 90 min. 3H-Adrenaline (A) plus 3H-noradrenaline(NA) increased much more slowly and reached a plateau 120-240 min after the injection. The approximate synthesis rate of adrenal A plus NA, calculated from the specific activity curves, ranged from 0.3 to 2.2 nmoles/h per kg b.w. The highest value was noted the first few minutes, the lowest 1-2 hrs after the administration of 3H-tyrosine. In some experiments subcellular fractionation of the adrenals was performed. In untreated animals the amount of DA and A plus NA recovered from the supernatant fraction was about 10 and 8 per cent, respectively, of the total amount recovered from the supernatant and particulate fractions. In the adrenals of animals receiving 3H-tyrosine 3.75 or 60 min beforehand these figures were significantly elevated whereas the DA and A plus NA of the particulate fraction did not deviate significantly from control values. The specific activities of 3H-DA were the same in the supernatant and particulate fractions within 3.75 min after the injection of 3H-tyrosine.


Apparent equilibrium constant between beta-adrenoceptors and a competitive antagonist on a cultured pacemaker cell of mammalian heart. Heart cells from newborn rats and kittens were cultured.  In both species the rate of pacemaker activity of single, cultured cells was increased by low concentrations of catecholamines.  Tthe beta-adrenoceptor blocker (minus)-KL255 antagonized competitively the effects of both, (minus)-noradrenaline and (minus)-isoprenaline.  A mean equilibrium constant of 3.6 times 10-10M between (minus)-KL255 and beta-adrenoceptors of single cells was estimated.


Variation in pH of plaque after a mouth rinse with a saturated solution of mannitol. Plaque pH changes were studied in a group of 18 persons after a mouth rinse for 30 seconds with a 50 per cent (w/v) solution of sucrose. One week later the experiment was repeated on the same group of persons, but then with a saturated solution of mannitol instead of sucrose. Dental plaque material was collected from 15 different areas equally distributed among all the teeth. The changes in H-ion concentration in plaque were studied 2, 5, 10, 20, and 30 minutes after the rinse. Saturated mannitol caused an insignificant pH-increase at 2 minutes after which the pH-values remained unchanged. The sucrose (50 per cent) markedly lowered the pH-value, with the lowest value at 5 minutes, after which it slowly rose. The differences were highly significant at all intervals.


Degradation of maltose and starch by human saliva and by supernatants of dental plaque material. The pH-decrease in dental plaque in vivo after mouth rinses with solutions of sucrose and maltose has been compared. No statistically significant differences were found between the results obtained with these two disaccharides. Pooled samples of parotid saliva, centrifuged whole saliva and dental plaque supernatants were separated with the isoelectric focusing technique. The results suggest that maltose is hydrolysed in parotid saliva by the salivary alpha-amylase and in dental plaque by enzymes from sources other than the salivary glands, probably microorganisms. No bacterial alpha-amylases, separated from salivary alpha-amylase, were found in whole saliva specimens or in dental plaque supernatants. Quantitative determinations of "maltase" and amylase activities in parotid saliva, centrifuged whole saliva and dental plaque supernatants from 10 subjects were carried out. The highest enzyme activity of "maltase" was found in the samples of dental plaque and the highest amylase activity in parotid saliva specimens.


Mechanism of skin penetration by Ancylostoma tubaeforme larvae. Skin penetration by infective Ancylostoma tubaeforme larvae has been investigated cinematographically and using in vitro techniques. The dermal tissue appears to cause little hinderance to larval migration but complete penetration through the skin from the dermal direction did not occur, although total penetration from the epidermal surface was frequently accomplished. No evidence could be found for enzymic secretions emanating from the worms under conditions that gave positive results from Necator americanus and Strongyloides fülleborni infective larvae. The results indicated that A. tubaeforme was able to penetrate without the use of enzymic secretions and an alternative, mechanical mechanism for penetration is advanced.


Placental transfer and fetal urinary excretion of gentamicin during constant rate maternal infusion. Placental transfer and fetal urinary excretion of gentamicin was studied in midtrimester goat and human previable fetuses during constant rate maternal infusion with the drug. Gentamicin was not detected in the serum of any of the goat fetuses, even when maternal serum concentrations ranged from 15.2 mug/ml to 20.9 mug/ml. However, gentamicin was present in the amniotic fluid of four animals. Gentamicin was also present in fetal urine collected from three animals. In contrast human fetal central venous serum concentrations of gentamicin were 21-37% of those in maternal serum after constant rate infusion of the mother. In addition, gentamicin was present in human fetal urine in concentrations 2-- 3 times those in fetal serum. The observed difference in fetal serum concentration of gentamicin between the two species represents a difference in placental permeability to gentamicin and/ or a difference in fetal renal clearance of the drug.


Blood sampling through umbilical catheters. An in vitro study testing the reliability of chemical determinations on blood samples withdrawn through an umbilical catheter is described. Blood samples were withdrawn through three different sizes of umbilical catheters containing a solution of dextrose, sodium bicarbonate, and potassium. Using either a 5 French or a 3 1/2 French catheter, accurate results were obtained for pH, sodium, potassium, and glucose when measurements were made after an initial 4-ml blood sample was discarded. With an 8 French catheter, accurate results were obtained for pH, sodium, and potassium but plasma glucose determinations remained inaccurate after 6 ml of blood was discarded.


Effect of low-frequency random noises on performance of a numeric monitoring task. Previous findings indicate that continuous low-frequency noises at moderate sound-pressure levels do not produce decrements in vigilance performance. Such noises are commonly found in urban environments, however; and it is important to explore their effects carefully. This study employed 27 human males in a numeric monitoring task to evaluate the effects of low-frequency (11.5 to 350 Hz) noise at moderate sound-pressure levels (80 db). More numeric signals were missed during noise than during control runs. The effect was small but statistically reliable (P smaller than .033), in disagreement with previous research. The possible environmental impact of these findings is discussed.


Unilateral brain lesions and MMPI performance: a preliminary study. Samples of 15 Ss with right- and 20 Ss with left-hemisphere brain lesions secondary to war-related penetrating missile wounds were matched for age, education, and recency of injury and evaluated with the MMPI. Right-hemisphere lesioned Ss produced a composite profile with all scales within normal limits. In contrast, the composite profile of left-hemisphere lesioned Ss showed significant elevations on the Sc, D, and Hs clinical scales, suggesting increased psychopathological responses in such Ss. Although the general configurations of the composite MMPI profiles in the two samples were similar, significant differences in the elevation of both validity and clinical scales were obtained. The results tend to support previous findings of a depressive-catastrophic reaction in patients with lesions in the dominant hemisphere, while not supporting the euphoric-indifference response in nondominant-hemisphere lesioned Ss.


Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse. Aequorin, a protein that emits light in the presence of calcium, was injected in the presynaptic terminal of the squid giant synapse. This injection was preceded by intracellular tetraethylammonium administration, which prolonged the duration of the presynaptic action potential. After this procedure light emission was evoked by single presynaptic spikes capable of releasing synaptic transmitter. In a second set of experiments, presynaptic tetraethylammonium injection was followed by the administration of tetrodotoxin extracellularly, which abolished the presynaptic action potential. Under these conditions artificial depolarization of the presynaptic terminal triggered the release of synaptic transmitter, in a graded manner. However, as previously reported by other authors, membrane potential steps to an internal positive value of approximately plus 90 mV (the suppression potential) produced a blockage of transmitter release for the duration of the imposed potential. Synaptic transmission recurred, nevertheless, as the current injection was terminated. A similar set of experiments, performed after the intracellular injection of aequorin in the presynaptic fiber, demonstrated that the aequorin light response was evoked by membrane potential steps capable of releasing synaptic transmitter. If the membrane potential was made positive to the "suppression" level, no light response was evoked but the light emission appeared, as did transmitter release, at the end of the current pulse. These experiments demonstrate that release of transmitter is directly correlated with intracellular calcium concentration and that the suppression potential is compatible with the existence of a calcium equilibrium potential at the presynaptic terminal.


Evidence for adenosine diphosphate ribosylation of Ca2+, Mg2+-dependent endonuclease. The molecular basis for the inhibition of the Ca2+,Mg2+-dependent endonuclease resulting from the formation of poly(adenosine diphosphate ribose) (ADP-Rib) was studies in a simplified system containing purified rat liver or bull semen endonuclease, purified rat liver poly(ADP-Rib) synthetase, [3H]NAD+, and DNA. Poly-(adp-rib) synthetase activity was stimulated when Ca2+, Mg2+-dependent endonuclease was added to the reaction mixture in place of histones, suggesting that the endonuclease can act as an acceptor for ADP-Rib. Evidence was presented to show that the ADP-Rib moiety of [3H]NAD+ was incorporated in the endonuclease fraction. The [3H]ADP-Rib bound to the endonuclease was in the form of monomers and oligomers and not long chain polymers. The present results suggest that the Ca2+,Mg2+-dependent endonuclease was ADP-ribosylated when the endonuclease was incubated with poly(ADP-Rib) synthetase and NAD+.


Breaking of seed dormancy by catalase inhibition. Germination of some dormant seeds is promoted by solutions of thiourea, sodium nitrite, and hydroxylamine salts. The promotions are accompanied by irreversible inhibition of catalase (EC 1.11.1.6) in extracts from the seeds. The seeds are also promoted in germination by catechol and pyrogallol solutions. These effects are recorded for lettuce (Lactuca sativa L. cv. Grand Rapids) and pigweed (Amaranthus albus L.) seeds. The results indicae that metabolically derived hydrogen peroxide, spared from decomposition by catalase inhibition, oxidizes reduced NADPH required as the oxidant in the pentose pathway of glucose use. The metabolic system for such use of H2O2 involves the enzymes, peroxidase (EC 1.11.1.7) and pyridine nucleotide quinone oxidoreductase (EC 1.6.99.2), which are present in the dormant seed prior to imbibition of water.


A kinetic study in vitro of the reoxidation of interchain disulfide bonds in a human immunoglobulin IgGLk. Correlation between sulfhydryl disappearance and intermediates in covalent assembly of H2L2. After reduction by dithiothreitol and removal of the reductant by molecular sieve chromatography, the four interchain disulfide bonds of the human IgGlk protein Fro reoxidize in the presence of oxygen and trace metal ions. The six molecular components of the reoxidation--L (light chain), H (heavy chain), HL, H2, H2L, H2L2--are quantitatively determined from polyacrylamide gels containing sodium dodecyl sulfate and the time-dependent sulfhydryl titer is measured with 5,5'-dithiobis-(2-nitrobenzoic acid). The rates of H2L2 covalent assembly depend on pH in an unexpected way: If the reduced protein is chromatographed at pH 3.2 and then adjusted to pH 7.5 (25 degrees, ionic strength equals 0.14), H2L2 formation proceeds rapidly, with half-times ranging between 20 and 40 min. In contrast, if chromatography is carried out at pH 5.5 before adjusting to the same final conditions, the half-times for H2L2 formation are considerably longer (120-180 min). The half-times in the former case approach the somewhat faster rates of H2L2 assembly observed in pulse-chase experiments with various types of mouse, IgG-producing cells [Baumal, et al. (1971) J. Exp. Med. 134, 1316-1334]. To facilitate comparison of experiments and models, we plot the concentrations of the six components against the corresponding number of sulfhydryl equivalents per mole of Fro. The respective plots for the pH 3.2 leads to 7.5 and 5.5 leads to 7.5 experiments are very similar despite the rate differences. Moreover, these plots differ significantly from the calculated plot for a hypothetical random reoxidation in which the intrinsic probability for formation of each correct HL and H2 disulfide bond is assumed equal and independent. It is concluded that the in vitro reoxidation of Fro (i) is other than random; (ii) involved a pathway of pathways with HL, H2, and H2L precursors; and (iii) involves at least some kinetic cooperativity in bond formation, since no model bases solely on independent bond formation adequately accounts for the results. The models were used also to examine the cellular assembly pathways of mouse IgG proteins.


Effects of maintenance amitriptyline and psychotherapy on symptoms of depression. Depressives responding to initial treatment were maintained on amitriptyline for eight months, withdrawn double-blind to placebo after two months, or withdrawn overtly onto no medication. In each group half the patients received weekly psychotherapy and half were seen once monthly. Effects on symptom ratings were examined. Maintenance amitriptyline gave a significant advantage over early withdrawal in preventing symptom recrudescence. There were no differences between double-blind or overt withdrawal. There were no interactions between drug withdrawal and psychotherapy. Psychotherapy produced no significant advantages over low contact on symptoms, although it did improve social adjustment ratings reported elsewhere.


The temporal and pathological significance of perfusion failure following renal transplantation. Serial dynamic studies with 99mTc-DTPA are a useful method of monitoring renal transplants. Radionuclide images obtained within 24 hours after surgery and at regular intervals thereafter can identify pathological conditions. The decline or absence of perfusion, coupled with the elapsed time following surgery, can be used to differentiate vascular occlusion or hyperacute rejection from acute rejection, acute tubular necrosis, or accelerated or chronic rejection. 99mTc-pyrophosphate can be used to simultaneously evaluate transplant function and locate possible aseptic necrosis of bone. Both studies are noninvasive and have been performed safely on numerous occasions over a period of several years.


Patterns of excretion of radioactive chelates in obstructive uropathy. Radioactive chelates such as 99mTc-DTPA are advantageous in ranal imaging, particularly in defining functional and morphological abnormalities of the excretory tract. In a review of more than 200 studies, 19 cases of lower-tract disease were diagnosed by the gamma camera image alone. In 16 of them, the diagnosis was confirmed by excretory urography. Normal radionuclide patterns are described and compared with the characteristic findings in caliectasis, hydronephrosis, and hydroureter. By facilitating evaluation of renal perfusion, renal glomerular function, and gross renal structure as well as good difinition of excretory function, radioactive chelate imaging is ideally suited for use as general screening test.


Pulmonary function studies and oxygen transfer in patients with liver cirrhosis and different degree of portasystemic encephalopathy. Pulmonary function and oxygen transfer was studied in five patients with cirrhosis of the liver and different degrees of portasystemic encephalopathy. Four patients were restudied after a change in CNS function. The contribution of various parameters of pulmonary gas exchange to the unsaturation found was evaluated employing the graphic analysis described by King and Briscoe. The following results were obtained: (1) there was no inequality of ventilation as judged by a nitrogen washout study; (2) a large true venous admixture was found in all patients; (3) in four patients studied twice venous admixture was larger when mean EEG frequency was lower; (4) besides the true venous admixture a low overall D/Q ratio was an important factor contributing to unsaturation in most cases; (5) in some cases a decreased overall V/Q ratio contributed to the unsaturation. This decreased V/Q ratio appeared to be due to an increase in pulmonary perfusion without a concomitant rise in ventilation. Changes in pulmonary perfusion pathways are suggested as the most likely cause of the defect in oxygen transfer found in patients with cirrhosis.


[Effects of drugs and environmental factors on ciliary movement (author's transl)]. The effects of a number of drugs, potassium and calcium ions, and air humidity on mucociliary function were studied in isolated preparations of rats bronchial tree. Adrenergic drugs increased the rate of ciliary beat significantly. Cilioexitation also occurred, though to a smaller degree, after application of acetylcholine, pilocarpine, aminophylline, prednisolone, KI and NH4C1. Serotonin, histamine, and acetylcystein did not change ciliary frequency to any significant degree; however, histamine in high concentrations caused ciliary incoordination. Codein and normetadon, nicotine and pentobarbital had a dose-dependent ciliodepressive effect. However, small concentrations of nicotine and pentobarbital were slightly stimulative. Methysergid and phentolamine were slightly ciliodepressive. Alterations of the concentrations of calcium and potassium ions in the nutritive solution influenced ciliary frequency but had no effect on other characteristic features of the ciliary movement. The ciliated epithelium of the bronchial tree could be irreversibly damaged by air having low relative humidity.


Deleterious effects of hyperbaric oxygen treatment on mortality and pathological changes in nitrogen-dioxide-poisoned dogs. Nitrogen dioxide poisoning was experimentally produced in dogs. PO2, PCO2 and pH were measured in poisoned animals and during treatment with hyperbaric oxygen (OHP) lung lesions in both groups were evaluated. It is concluded that OHP has a deleterious effect both in terms of mortality and pathological changes.


Interaction between local anesthetics and analeptic drugs. Although clinicall undesirable, the fortuitous pharmacologic interactions between local anesthetic agents and analeptic drugs may be protective when large doses of both agents are used. Mice pretreated with procaine, lidocaine, and tetracaine had a lower incidence of seizures when convulsive doses of either nikethamide or doxapram hydrochloride were given intraperitoneally. Mortality was also decreased in the groups given nikethamide and was zero in the animals treated with doxapram. All animals treated with pentylenetetrazol convulsed and only lidocaine (also used as an anticonvulsant) was able to reduce mortality in this group. Of the local anesthetic agents, tetracaine afforded the least protection from death, whereas lidocaine seemed to be most effective.


Vascular spider: a cutaneous manifestation of hyperdynamic blood flow in hepatic cirrhosis. Arteriography and gas analysis of blood aspirated from a vascular spider in a patient with hepatic cirrhosis were done before excision and histologic examination of the lesion. This study supports earlier work suggesting that a spider angioma is a cutaneous manifestation of a generalized hyperdynamic circulation in hepatic cirrhosis. Moreover, based upon a variety of experimental and clinical observations on the splanchnic circulation in cirrhosis, it is suggested that the portal hypertension blood flow encounters the obstacle posed by the scarred liver ("active congestion").


Fatal paralytic ileus complicating phenothiazine therapy. The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.


Cytotoxic macrophage in graft-versus-host reaction. Peritoneal macrophages of F1 hybrid mice injected with parental strain spleen cells 8-14 days previously ("early" graft-versus-host (GVH) macrophages) develop an increased ability to destroy in vitro bystanding target cells of syngeneic, allogeneic, and xenogeneic origin. At later stages of GVH reaction, the nonspecific cytotoxicity of macrophages wanes ("late" GVH macrophages) and does not differ much from that of control macrophages. Trypsinization of early GVH macrophages or iodoacetate treatment significantly reduces their cytotoxicity, whereas anti-theta serum and complement have only a moderate effect. Antimouse IgM antibody significantly enhanced the cytotoxic potential of early GVH macrophages, but had no effect either on normal or late GVH macrophages. In contrast, antimouse IgG antibody enhanced, although slightly, only the cytotoxic activity of late GVH macrophages. Two possible explanations of the increased cytotoxicity of early GVH macrophages are offered: (1) cytophilic antibody of IgM type, directed against host antigens, renders macrophages capable of damaging nonspecifically bystanding target cells upon contact with antigen; (2) IgM alloantibody produced by parental cells changes the surface properties of macrophages and contributes to the cytotoxicity of these cells.


Inhibition of the graft-versus-host reaction. III. Altered in vivo distribution of spleen cells pretreated with Fab fragments of antithymocyte globulin. 51Cr-labeled parental strain spleen cells were pretreated in vitro with antithymocyte globulin (ATG) or Fab fragments of ATG before i.v. injection into F1 recipients. Recipients were killed at various intervals after injection and their organs were assayed for radioactivity in order to determine the in vivo distribution pattern of pretreated cells. 51Cr spleen cells pretreated with ATG were almost totally prevented from migrating to spleens, lymph nodes, bone marrow, Peyer's patches, lungs, and peripheral blood of recipients. Pretreatment of 51Cr spleen cells with noncytotoxic Fab of ATG also inhibited localization to these organs and tissues; however, the inhibition was not as complete as that of ATG-treated cells. Localization of Fab-treated 51Cr spleen cells to recipient nodes was inhibited to a greater extent than was localization to recipient spleens. There was no significant difference in the extent of inhibition of ATG-treated 51Cr spleen cells to recipient nodes and spleen. Organ counts from recipients killed at various intervals after injection of Fab-treated 51Cr spleen cells showed that Fab-treated cells do not recover their recirculating potential in vivo.


Specific unresponsiveness to skin allografts in mice. IV. Immunological reactivity of mice treated with liver extracts, Bordetella pertussis, and antilymphocyte serum. The strain-specific unresponsiveness to H-2 incompatible skin allografts induced by treatment of adult mice with single inoculations of donor strain liver extract and Bordetella pertussis vaccine, as well as three doses of antilymphocyte serum, has been investigated by several in vivo and in vitro methods, with a view to elucidating it mechanism. Lymphoid cells from mice with long surviving skin grafts were found to be reactive in graft-versus-host assays (as measured by splenomegaly or popliteal lymph node enlargement), and mixed lymphocyte culture tests gave positive results. Attempts to cause lethal runting of F1 hybrid mice injected at birth with spleen cells from unresponsive mice gave variable results. However, the injection of F1 hybrid cells into the footpads of unresponsive animals failed to elicit a significant host-versus-graft response. Although lymphoid cells from unresponsive animals did not include detectable numbers of cytotoxic cells, such cells could be generated by previous in vitro mixed lymphocyte culture stimulation or, to some degree, by the injection of the animals with F1 hybrid cells. Attempts to prevent mixed lymphocyte culture stimulation or cytotoxicity with serum from unresponsive mice failed at the serum concentrations used. The data indicate that long-term unresponsiveness in this system is maintained by the production in the hosts of factors that interfere with the cell-mediated response.


[Corticosteroid hormones and histones (on the mechanism of action of hormones)]. The role of interaction between corticosteroid hormones and histones is considered with regard to hormonal activation of genes and some secondary changes of cells functional condition due to the presence of the hormones.