Reversal of B-cell immunization or tolerization by specific enzymatic degradation of antigen. The mechanism of B-cell immunity or tolerance reversal by enzymatic treatment, was studied on cells stimulated in vitro by T-independent antigens, either sensitive or insensitive to enzymatic hydrolysis. B-cell stimulation induced by spleen cell incubation with DNP coupled to polymer was reversed when antigen-pulsed cells were treated with enzymes specifically hydrolytic for the carrier. Cell treatment with proteases abolished the response induced by DNP-POL (polymerized flagellin). Immunity or tolerance remained unchanged when induced by DNP conjugated to D-GL (D-glutamic and D-lysine copolymer) or to dextran B512 or B1299. While DNP-POL is a substrate for proteases, the latter three components are insensitive to the hydrolytic action of protease. B cells, preincubated with DNP-B512, were rescued from tolerance by dextranase treatment. Immunity and tolerance remained unchanged when induced by DNP-POL, DNP-B512 and DNP-B1299. While DNP-B512 was totally hydrolysed by dextranase, the latter three conjugates were not. These results show that (a) the initial stage for the induction of either immunity or tolerance is reversible, (b) the target of the enzymatic effect is the antigen itself, and (c) the interaction between polymeric antigen and B-cell Ig receptors is not sufficient to drive the cell to an irreversible stage of differentiation.


Comparative inhibition beta-lactamases by novel beta-lactam compounds. The beta-lactamase-inhibiting activity of CP-45,899, 3,3-dimethyl-7-oxo-4-thia-1-azabicylo(3,2,0)heptane-2-carboxylic acid, 4,4-dioxide [2S-(2alpha,5alpha)], was investigated and compared with the beta-lactamase-inhibiting activity of clavulanic acid and dicloxacillin. CP-45,899 was an effective inhibitor of Staphylococcus aureus beta-lactamase and of those beta-lactamases of gram-negative bacteria which are primarily active against penicillins or equally active against penicillins and cephalosporins. The reaction of CP-45,899 with beta-lactamases was a concentration- and time-dependent event. CP-45,899 acted as a competitive inhibitor of plasmid-mediated S. aureus, Escherichia coli, and Shigella sonnei beta-lactamases and inducible Klebsiella beta-lactamase. CP-45,899 was a poor inhibitor of inducible or constitutive chromosomally mediated beta-lactamases of indole-positive Proteus, Citrobacter, and Enterobacter. CP-45,899 had lower kinetic constants for inhibition of hydrolysis than did clavulanic acid against many of the beta-lactamases which both inhibited.


Strain of Trichomonas vaginalis resistant to metronidazole and other 5-nitroimidazoles. A strain of Trichomonas vaginalis (IR-78), recently isolated from a patient afflicted with recurrent symptomatic trichomoniasis, showed resistance to metronidazole, tinidazole, and nimorazole in vitro as well as in vivo. In a serial dilution test using cysteine monohydrochloride-peptone-liver infusion-maltose medium, T. vaginalis IR-78 was only resistant under aerobic conditions. Under anaerobic conditions it was as susceptible as the normal reference strain. The minimal lethal concentrations of metronidazole, tinidazole, and nimorazole for IR-78 were 100, 50, and 50 mug/ml aerobically and 0.4, 0.4, and 0.2 mug/ml anaérobically, respectively. The efficacy of metronidazole, tinidazole, and nimorazole was assessed in vivo by oral administration to mice simultaneously infected with IR-78 both subcutaneously and intraperitoneally. The CD(50) (dose needed to cure 50% of infections) of each compound was significantly higher for the subcutaneous than for the intraperitoneal infection. In contrast, there was little difference in CD(50) for these infections in mice inoculated with a susceptible trichomonas strain. The CD(50)'s for all three compounds against intraperitoneal and subcutaneous infections with IR-78 were 2 to >70 times higher than for susceptible strain E. Both forms of infection with IR-78 could always be cured with therapeutically acceptable doses of tinidazole and nimorazole; subcutaneous infections could not be cured with tolerated doses of metronidazole.


Plasmid-mediated ampicillin resistance in Haemophilus ducreyi. Three of 19 strains of Haemophilus ducreyi, isolated during a recent outbreak of chancroid, were found to produce beta-lactamase and to harbor a 6.0 x 10(6)-dalton plasmid. Escherichia coli transformed with this plasmid acquired beta-lactamase-mediated resistance to ampicillin. The guanine-plus-cytosine content of the plasmid was found to be 41 mol%. Restriction endonuclease digestion studies suggest that a relatively large portion of the Tn1 translocon is carried by this plasmid. Whereas this plasmid could not be transferred to H. influenzae by mating on membrane filters, a strain of H. ducreyi was able to receive and donate a 30 x 10(6)-dalton ampicillin resistance plasmid from H. influenzae. The ability of H. ducreyi to receive and donate conjugative plasmids may result in the appearance of multiply resistant strains.


Effect of clavulanic acid on the minimum inhibitory concentration of benzylpenicillin, ampicillin, carbenicillin, or cephalothin against clinical isolates resistant to beta-lactam antibiotics. The effect of clavulanic acid on the minimum inhibitory concentration of benzylpenicillin, ampicillin, carbenicillin, or cephalothin against 353 clinical isolates of penicillin- and/or cephalothin-resistant strains was estimated.


Cell-mediated immunity in vitro in atopic dermatitis. The function of T cells in atopic dermatitis was studied by leukocyte migration agarose and lymphocyte transformation tests. We found that phytohemagglutinin (PHA)-  and PPD-induced release of leukocyte migration inhibition factor (LIF) from lymphocytes is significantly decreased (P less than .001) in patients with atopic dermatitis as compared with healthy controls. Blastogenic response of lymphocytes induced by PPD was also decreased in atopic patients as compared with controls (P less than .01). No differences were found in spontaneous blastogenesis or in blastogenic response of lymphocytes in vitro to PHA, concanavalin A (ConA), or streptokinase-streptodornase (SK-SD) between patients with atopic dermatitis and controls.


Thoracoscopy in children.

Thoracoscopy in children. Dissatisfied with standard techniques for pulmonary diagnosis in children, we have evaluated the usefulness of thoracoscopy for diagnosis of intrathoracic pathology. Between July 1, 1975, and May 1, 1978, 65 thoracoscopy procedures have been performed in 57 children at the University of Florida. Thirty-four procedures were performed in immunosuppressed patients to rule out Pneumocystis carinii pneumonia. Twenty of these patients were proven to have Pneumocystis pneumonia, a diagnostic accuracy of 100%. Twelve nonimmunosuppressed patients underwent thoracoscopy for the diagnosis of persistent pulmonary infiltrates with a 100% diagnostic accuracy. Fifteen procedures were performed for the diagnosis of intrathoracic tumors. In two patients, previously unsuspected areas of involvement were encountered while in two patients false-negative biopsies were obtained. Four patients underwent therapeutic thoracoscopy. In three small infants, unsuccessful attempts were made to unroof pulmonary cysts through the thoracoscope and one patient underwent a talc poudrage. Thoracoscopy has proven to be a safe and rapid procedure which may be performed under local anesthesia without need for endotracheal intubation. In patients with pulmonary infiltrates, the accuracy has been 100%. The capability of viewing the entire hemithorax has proven valuable in evaluating children with intrathoracic tumors. Complications have included pneumothorax in six patients and bleeding in two.


Selective intra-arterial vasopressin: clinical efficacy and complications. A retrospective analysis of results obtained over a three year period in 66 patients receiving selective intra-arterial vasopressin (SIAV) for control of 69 episodes of massive gastrointestinal bleeding was presented. SIAV was used when there was a failure of conventional medical therapy and the patient's pathology and/or complicating medical conditions necessitated an attempt at controlling an emergent condition by nonoperative means. Hemmorrhage was completely controlled in 43% of variceal bleeds, 67% of hemorrhage gastritis, 45% of bleeding ulcers, and in 62% of colonic sources. The incidence of rebleeding following initial control was 16%. The surgical mortality for patients who were initial failures of SIAV was 50%. Patients undergoing elective surgery after complete control by SIAV had an 8% mortality. There were five catheter related complications. Minor complications occurred in 41% of patients, but required no treatment. Major complications occurred in 40% of cirrhotic and 21% of noncirrhotic bleeding episodes; and were a contributing factor in five cirrhotic deaths and three noncirrhotic deaths. In critically ill patients in the setting of an Intensive Care Unit, selective intra-arterial vasopressin appears: 1) to be  an effective means of controlling certain types of gastrointestinal hemorrhage; 2) to provide an opportunity for an increase in survival rate.


Acute systemic anaphylaxis in adult domestic fowl--possible role of vasoactive lipids and peptides. Bovine albumin (BA: 2 mg/kg-1, i.v.) produced a fall in systemic arterial blood pressure accompanied by central venous hypertension and bradycardia in pentobarbital-anaesthetized, spontaneously breathing, bovine albumin-sensitized adult domestic fowl. Trasylol (a potent inhibitor of kallikreins) suppressed acute systemic anaphylaxis. Polyphloretin phosphate (an effective antagonist of PGF2alpha) also inhibited the cardiovascular responses to antigen and PGF2alpha. Sodium meclofenamate and phenylbutazone showed varying degree of blockade of cardiovascular responses to exogenously administered chemical mediators (bradykinik, PGF2alpha, SRS-A and to a lesser extent of histamine, 5-HT and acetylcholine) and antigen. Indomethacin (virtually devoid of receptor blocking activities toward exogenously injected chemical mediators) inhibited anaphylaxis. The results of this investigation strongly suggested an important role of vasoactive lipids and polypeptides in avian anaphylaxis.


Haemophilus influenzae cellulitis in an adult. Cellulitis due to Haemophilus influenzae type B in adults has only recently been reported. We report a case in which the patient's antibody levels documented an immunologic response to the organism. The efficacy of a new cephalosporin antibiotic, cefoxitin sodium, in treating this infection also was established. Cefoxitin has activity against ampicillin-resistant H influenzae and would be an alternative in treating H influenzae cellulitis.


Human mammary carcinoma cells. The enzyme pacemaker profibrinolysin. When cultured in-vitro, originating from different breast cancer patients, tumor cells, identified histologically as carcinoma cells, varied in their proliferation patterns and cell morphology. If exposed for brief periods to vibrio cholera neuraminidaes (VCN), the amount of sialic acid released from the cells varied from one culture to another and increased with higher enzyme concentrations. If exposed to trypsin, the amount of released proteins varied also from one culture to another. Significant difference was observed between the effect of VCN or collagenase on normal and neoplastic cell cultures. Whether human or murine cell cultures, the cell-free media harvested from cultures of neoplastic cells containing high concentrations of collagenolytic-caseinolytic-fibrinolytic and esterolytic activities. Two effects of concanavalin A (Con A) have been distinguished on thymidine incorporation, the first is a decrease in the maximal thymidine uptake, whereas the second is a shift to the maximum thymidine uptake to higher Con A concentrations. At low concentrations, alpha-1-antitrypsin (AAT) had no effect, but at high concentrations it inhibited 3H-thymidine uptake. At low concentrations human profibrinolysin inhibited and at higher concentration sit enhanced uptake of the labeled precursor. Therefore, the collagen olytic caseinolytic-fibrinolytic enzyme is a pacemaker for proliferation of human mammary carcinoma cells.


Lymphocyte sequestration by the liver in alcoholic hepatitis. The possibility that lymphocytes are sequestered by the liver in patients with alcoholic hepatitis was investigated. Sixteen patients who had liver biopsy specimens taken were studied as follows: The T- and B-lymphocyte populations of the peripheral blood and liver biopsy digest were quantitated. The liver biopsy specimens were studied by light and electron microscopy for lymphocyte-hepatocyte interaction. The data were analyzed by comparing the results of patients with and without the presence of Mallory bodies (MBs) in the liver. When MBs were present, the percentage of T cells was significantly increased in the liver compared with peripheral blood. By electron microscopy, two livers with MBs showed lymphocyte-hepatocyte interaction. The results support the concept that lymphocytes participate in a cell-mediated immune process when MBs are present in the liver.


Gastroduodenal disease in chronic spinal cord injuries. An endoscopic study. Endoscopic study of the upper gastrointestinal tract was performed in 40 patients in the chronic stage of spinal cord injury. Of these, 37 patients were analyzed for endoscopic abnormalities, symptoms, and physical findings. Nineteen patients (51.4%) had abnormalities by endoscopy. There were 11 gastric erosions, two gastric ulcers, and six cases of congestion or submucosal hemorrhage. In addition, five patients had duodenal mucosal lesions. An attempt to find clear diagnostic clues in terms of symptoms or physical signs was unsuccessful. Anorexia and nausea were early symptoms to which we should pay attention. The results do not permit an assessment of the relation of various possible causative factors and these gastroduodenal lesions. The study does call attention to the high incidence of gastroduodenal lesions in these patients.


Symposium on membrane markers and antigens of human lymphocytes and leukemic cells. B lymphocytes, mediators of humoral immunity, carry easily detectable SIg, form rosettes with RBC coated with IgM and complement (EAC rosetting) and bind aggregated Ig (Fc receptor activity). Human T lymphocytes, mediators of cellular immunity, lack a specific antigen found on mice T lymphocytes (theta antigens). They form spontaneous (non-immune) rosettes with SRCB (E rosetting) and they are identified by labelling or cytotoxicity tests wtih heterologous antisera. Apart from B and T lymphocytes, a third population of lymphoid cells carrying no detectable surface markers have been identified by various methods (Null cells).


Human serum thymic factor in detecting acute T cell leukemia. In acute leukemia, the frequency of the E+ cells among the blood mononuclears before and after their incubation with human serum thymic factor was investigated by means of the E rosette assay. In 4 of 24 patients tested, the thymic factor incubation of their peripheral blood cells increased the number of the E+ cells among the mononuclears. Prospective importance of the test either in investigating whether a T0 leukemia might really exist, or in monitoring possible variations of the immature T cell counts in relationship to the patient's treatment and his disease course, are discussed.


A chemical-modification approach to the olfactory code. Studies with a thiol-specific reagent. The effects of thiol-specific reagents on the amplitude of the electro-olfactogram (E.O.G.) responses elicited from frog olfactory mucosa by pulses of odorant vapours was studied. The impermeant thiol-specific reagent mersalyl [(3-{[2-(carboxymethoxy)-benzoyl]amino}-2-methoxypropyl)hydroxymercury monosodium salt] brings about a rapid decrease in the E.O.G. signal obtained with the odorant pentyl acetate. The extent of the decrease is proportional to the concentration of the mersalyl applied and the effect of the reagent is partially but incompletely reversed by treatment of the labelled mucosa with dithiothreitol. The sites labelled by mersalyl can be protected by pretreating the mucosa with a dilute solution of the odorant pentyl acetate and leaving the solution in contact with the tissue after the addition of mersalyl. When the protecting odorant is washed out of the tissue, the original E.O.G. amplitude is regained. Pentyl acetate applied to the mucosa protected the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: n-butyric acid, n-butyl acetate, phenylacetaldehyde and cineole (1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane). The pentyl acetate applied to the mucosa failed to protect the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: butan-1-ol, benzyl acetate, nitrobenzene, beta-ionone and linalyl acetate. The significance of the differential protection effects for the odour-quality-coding mechanism in the olfactory primary neurons is discussed. It is suggested that the olfactory code at this level of the olfactory system may be elucidated by chemical-modification methods.


Idiopathic edema as a cause of nonarticular rheumatism. Six women, aged 24 to 53, presented with symptoms of diffuse aching, morning stiffness, and fatigue, but demonstrated no objective abnormalities on joint examination or in laboratory studies. Each was found to have idiopathic edema, a disorder of fluid retention probably related to an abnormality of capillary permeability in which transudation of fluid into the subcutaneous tissues of dependent parts may result in swelling and discomfort. The rheumatic symptoms improved when therapeutic measures were directed against the accumulation of edema fluid. This syndrome may account for a minority of cases of nonarticular rheumatism in women.


Inheritance of porcine von Willbrand's disease: study of a kindred of over 700 pigs. A study of over 700 pigs affected with von Willebrand's disease suggests that the classic disease is transmitted as an autosomal recessive trait. Less clear is the genetic basis of inheritance of variant types of this disease produced by selective mating.


Failure of indomethacin to close persistent ductus arteriosus in infants weighing under 1000 grams. Six preterm infants with a persistent ductus arteriosus, who failed to improve with conventional medical management, received indomethacin in an attempt to close the duct pharmacologically. All infants weighed less than 1000 g when the drug was administered. All showed a transient response to indomethacin; however, no infant demonstrated a permanent response, even though 5 of the 6 received multiple doses. One of the patients developed a severe episode of anuria, uraemia, and gastrointestinal bleeding. Of the 6 infants, 3 underwent subsequent successful surgical ligation of the ductus. It is suggested that the extremely preterm infant may be a 'poor responder' to indomethacin. Since the side effects of indomethacin may be life-threatening, it may be wise to consider surgical ligation in lieu of indomethacin administration in these infants.


[Systemic lupus erythematosus in pediatrics]. Herein we present our experience with 16 children in whom the diagnosis of SLE was established between May 1974 and April 1978. In eleven of them renal biopsy was performed. Five had family history of immunologic disease. Only one patient had history of anticonvulsant drug intake. The clinical picture resembles adult SLE, where the most frequent symptoms were arthritis, fever and dermatosis. Three patients showed focal proliferative glomerulonephritis; another 3, increased mesangial cellularity; 3 more presented diffuse proliferative glomerulonephritis and another one had membranous glomerulonephritis. LE cells, antinuclear antibodies, anti-DNA were present in various combinations in all patients. Treatment with an average dose of 22.8 mg/day of prednisone, plus immunosuppressive therapy in 9 patients, has allowed a 36 months survival in 13 patients. Progressive renal involvement and tuberculosis were the cause of death in 3 cases. Our results are compared with those in the literature.


Arterial counterpulsation in severe refractory heart failure complicating acute myocardial infarction. The role of arterial counterpulsation was sought in 100 patients with severe refractory cardiac failure complicating myocardial infarction. Seventy-four were in shock and 26 were not. Average duration of counterpulsation was 7.0 days. Hospital survival was 34 per cent (25/74) in shock (predicted less than 10%) and 65 per cent in patients who were not in shock (predicted less than 50%). Survival at 4 years was 10 +/- 4 per cent in shock and 37 +/- 11 per cent in patients not in shock; functional status was class 1 or 2 in 5 of 9 patients in shock and in 8 of 12 survivors not in shock. Results were best when counterpulsation was started early after onset of symptoms, when ischaemic pain was still present, or when a mechanical defect was corrected surgically. Early coronary artery bypass surgery performed alone in 9 patients did not influence survival or functional status. Complications of counterpulsation occurred in 17 patients in shock and in 2 patients not in shock, all but 6 on the first day; none directly caused death. Counterpulsation is an effective and safe adjunct to medical treatment of complicated infarction provided the intervention is prompt.


[Miliary tuberculosis in 27 children].

[Miliary tuberculosis in 27 children]. In the course of 3 1/2 years, 27 children with miliary tuberculosis were seen at the Hospital Infantil Lorencita Villegas de Santos in Bogotá, Columbia. Twenty-six percent of cases were infants under 12 months of age. Typical clinical cases were malnourished patients with impairment of their general condition, light respiratory stress or neurologic meningoencephalic involvement and febrile syndrome having a high contact index with tuberculous relatives. Some of them were undergoing measles or whooping cough convalescence. The chest X-ray showed micronodular infiltration and some cases, with hiliar adenomegaly, effusion or caverns. The liver percutaneous biopsy was of great help. The isolation of the bacillus from exudates was difficult to achieve. Tuberculin test was positive only in 30%. Cause of death: infiltration of central nervous system.


Uptake of catecholamines by human cardiac muscle in vitro. Noradrenaline uptake was studied using heart muscle from 102 patients undergoing cardiac surgery. Slices of right atrium were incubated in Krebs-Henseleit solution containing 1.3 x 10(-7) M 3H-noradrenaline. Uptake was lower in failing heart muscle and was inhibited not only by increasing the noradrenaline concentration in the incubating medium but also by adding the drugs desmethylimipramine, amitryptyline, and ouabain.


Dermatitis herpetiformis and Sjögren's syndrome. Two patients are described with dermatitis herpetiformis and Sjögren's syndrome. The increased incidence of autoantibodies in dermatitis herpetiformis would suggest that this association is significant. Antinuclear antibodies commonly occur in dermatitis herpetiformis (Seah et al,, 1971) yet are rarely associated with autoimmune disease in these patients (Moncada, 1974). This report records two patients with dermatitis herpetiformis and Sjögren's syndrome.


Two populations of factor VIII-related antigen in a family with von Willebrand's disease. The factor VIII-related antigen in a patient with von Willebrand's disease showed increased anodal mobility on two-dimensional immunoelectrophoresis. However, the antigen present in several of this patient's relatives showed two distinct peaks, one in the normal position and one similar to that of the patient. Very little of the patient's antigen could be recovered from ethanol precipitates or cryoprecipitates of whole plasma. Only the slower component could be recovered from the precipitates prepared from plasma of these family members showing two populations of antigen, the faster moving antigen remaining in the supernatant. This antigen of increased mobility corresponds very closely to that remaining in the supernatant of normal plasma, following similar fractionation procedures. It is suggested that the factor VIII-related antigen in some variant forms of von Willebrand's disease is a normal component of plasma, present in increased amounts.


A study of birth weight, placental weight and mortality of twins as compared to singletons. A study was made of 1655 sets of twins born between 1931 and 1975 in two clinical centres. Compared to singletons, twins were born three weeks earlier, weighed less at birth from 33 weeks to term and had smaller placentae from 21 to 22 weeks to term. The influence on birth weight fo sex was smaller in twins, the influence of parity greater. Because, compared to singletons, lower placental indices were found in twins up to 37 to 38 weeks, the conclusion is drawn that the retardation of growth in twins is to some extent due to the placenta itself. When singletons and twins of the same gestational age were compared, the mortality was found to be similar, somewhat lower in twins up to 37 to 38 weeks and higher afterwards. Monochorial twins were found to be born earlier, weigh less at birth and have a higher mortality than dichorial twins. Placental weights were not different and the conclusion is drawn that the retardation of growth in monochorial twins is to some extent due to the higher incidence of marginal and velamentous insertions of the umbilical cord associated with lower birth weights.


Effect of normal pregnancy upon the glycosylated haemoglobins. In this cross-sectional study total glycosylated haemoglobin (Hb AIa+b+c) has been measured in 20 healthy non-pregnant women and in five groups of 20 healthy women at various times during pregnancy. A statistically significant decrease occurs in these minor haemoglobin fractions by about 20 weeks gestation and this reduced level is maintained throughout the rest of pregnancy. If diabetic patients are to have their control assessed during pregnancy by determination of these fractions this fact might be relevant.


Bilateral symmetry of vision disorders in typical retinitis pigmentosa. Bilateral symmetry of disorders of vision is examined in 60 typical patients with retinitis pigmentosa.  We observed a very high degree of interocular congruence in the patterns of both kinetic visual field defects and threshold profiles and in abnormalities of foveal colour discrimination and visual acuity.  Abnormalities of foveal colour vision are highly correlated with the extent of visual field loss.


The involvement of iron and ubiquinone in electron transfer reactions mediated by reaction centers from photosynthetic bacteria. Reaction centers from Rhodopseudomonas sphaeroides strain R-26 were prepared with varying Fe and ubiquinone (Q) contents. The photooxidation of P-870 to P-870+ was found to occur with the same quantum yield in Fe-depleted reaction centers as in control samples. The kinetics of electron transfer from the initial electron acceptor (I) to Q also were unchanged upon Fe removal. We conclude that Fe has no measurable role in the primary photochemical reaction. The extent of secondary reaction from the first quinone acceptor (QA) to the second quinone acceptor (QB) was monitored by the decay kinetics of P-870+ after excitation of reaction centers with single flashes in the absence of electron donors, and by the amount of P-870 photooxidation that occurred on the second flash in the presence of electron donors. In reaction centers with nearly one iron and between 1 and 2 ubiquinones per reaction center, the amount of secondary electron transfer is proportional to the ubiquinone content above one per reaction center. In reaction centers treated with LiClO4 and o-phenanthroline to remove Fe, the amount of secondary reaction is decreased and is proportional to Fe content. Fe seems to be required for the secondary reaction. In reaction centers depleted of Fe by treatment with SDS and EDTA, the correlation between Fe content and secondary activity is not as good as that found using LiClO4. This is probably due in part to a loss of primary photochemical activity in samples treated with SDS; but the correlation is still not perfect after correction for this effect. The nature of the back reaction between P-870+ and Q-B was investigated using stopped flow techniques. Reaction centers in the P-870+ Q-B state decay with a 1-s half-time in both the presence and absence of o-phenanthroline, an inhibitor of electron transfer between Q-B and QB. This indicates that the back reaction between P-870+ and Q-A is direct, rather than proceeding via thermal repopulation of Q-A. The P-870+ Q-B state is calculated to lie at least 100 mV in free energy below the P-870+ Q-A state.


Energetics of coupled Na+ and Cl- entry into epithelial cells of bullfrog small intestine. Na+, K+ and Cl- concentrations (cij) and activities (aij), and mucosal membrane potentials (Em) were measured in epithelial cells of isolated bullfrog (Rana catesbeiana) small intestine. Segments of intestine were stripped of their external muscle layers, and bathed (at 25 degrees C and pH 7.2) in oxygenated Ringer solutions containing 105 mM Na+ and Cl- and 5.4 mM K+. Na+ and K+ concentrations were determined by atomic absorption spectrometry and Cl- concentrations by conductometric titration following extraction of the dried tissue with 0.1 M HNO3. 14C-labelled inulin was used to determine extracellular volume. Em was measured with conventional open tip microelectrodes, aiCl with solid-state Cl-selective silver microelectrodes and aiNa and aiK with Na+ and K+-selective liquid ion-exchanger microelectrodes. The average Em recorded was -34mV. ciNa, ciK and ciCl were 51, 105 and 52 mM. The corresponding values for aiNa, aiK and aiCl were 18, 80 and 33 mM. These results suggest that a large fraction of the cytoplasmic Na+ is 'bound' or sequestered in an osmotically inactive form, that all, or virtually all the cytoplasmic K+ behaves as if in free solution, and that there is probably some binding of cytoplasmic Cl-. aiCl significantly exceeds the level corresponding to electrochemical equilibrium across the mucosal and baso-lateral cell membranes. Earlier studies showed that coupled mucosal entry of Na+ and Cl- is implicated in intracellular Cl- accumulation in this tissue. This study permitted estimation of the steady-state transapical Na+ and Cl- electrochemical potential differences (deltamuNa and deltamuCl). deltamuNa (-7000 J . mol-1; cell minus mucosal medium) was energetically more than sufficient to account for deltamuCl (1000--2000 J . mol-1).


A sensitive bioassay for lipase using bacterial bioluminescence. A new bioassay for lipase utilizes a dim mutant of luminous bacteria which emit light upon the addition of long chain fatty acids, especially myristic acid. The luminescence response is proportional to the amount of added myristic acid over a 100-fold range, down to 10 nM. Trimyristin was used as a substrate for lipase and the hydrolyzed myristic acid was determined by the response of the luminous bacteria either on a continuous basis in the same reaction mixture or alternatively, when the hydrolytic stage is done separately followed by the independent detecting system. Using these procedures it is possible to assay lipase activity at rate corresponding to a release of as low as 10 pmol myristic acid per min.


omega-Oxidation of fatty acids and the acetylation p-aminobenzoic acid. p-Aminobenzoic acid was fed to normal and alloxan-induced diabetic rats injected with [omega-14C]labeled and [2-14C]labeled fatty acids. The p-acetamidobenzoic acid that was excreted was hydrolyzed to yield acetate which was degraded. The distribution of 14C in the acetates formed when an [omega-14C]labeled fatty acid was injected was similar to that when a [2-14C]labeled fatty acid was injected. This contrasts with the finding that in acetates from 2-acetamido-4-phenylbutyric acid excreted when 2-amino-4-phenylbutyric acid was fed, there was a difference in the distributions of 14C, a difference attributable to omega-oxidation of the fatty acid. Acetylation of p-aminobenzoic acid is then concluded to occur in a different cellular environment than that of 2-amino-4-phenylbutyric acid, one in which omega-oxidation is not functional. When 2-amino-4-phenylbutyric acid was fed and [6-14C]palmitic acid injected, rather than [16-14C]palmitic acid, the distribution of 14C in acetate was the same as when [2-14C]palmitic acid was injected. This indicates that the dicarboxylic acid formed on omega-oxidation of palmitic acid does not undergo beta-oxidation to form succinyl-CoA. Thus, glucose is not formed via omega-oxidation of long-chain fatty acid.


Individual assignments of amide proton resonances in the proton NMR spectrum of the basic pancreatic trypsin inhibitor. Studies of proton-proton nuclear Overhauser effects were used to obtain individual assignments of 17 amide proton resonances in the 360 MHz proton nuclear magnetic resonance spectrum of the basic pancreatic trypsin inhibitor. First, optimizing the conditions for obtaining selective nuclear Overhauser effects in the presence of spin diffusion in macromolecules is discussed. Truncated driven nuclear Overhauser experiments were used to assing the amide proton resonances of the beta-sheet in the inhibitor. It is suggested that these techniques could serve quite generally to obtain individual resonance assignments in beta-sheet secondary structures of proteins. Combination of nuclear Overhauser studies with spin decoupling further resulted in individual assignments of the gamma-methyl resonances of the two isoleucines and numerous Calpha and Cbeta protons.


[Evaluation of the protective action of diphosphonic compounds against a T-lymphocyte lesion by antilymphocyte serum]. Rabbit antilymphocyte serum (ALS) and complement were used in doses killing 50% of lymphocytes (staining with a 1% solution of trypan blue). In rosette-forming and blast-cell transformation reactions the counts of rosette forming and transformed cells were 60 and 24% respectively, as compared to those in controls. After adding 0.1 ml of 10 mM solution of potassium hydroxyethylene-diphosphonate belonging to a group of synthetic diphosphonates, the protective effect was observed shown by that the counts of rosette-forming and transformed lymphocytes did not differ from the control ones, wherein the reactions were produced with intact cells.


Cell-factor interaction and factor-dependant long-term growth of human T-progenitor cells. Specific cell-factor interactions provide a basic mechanism for differentiation of myeloid and lymphoid cells. Evidence at the present time indicates that factor-producing cells, factor and factor-responding cells are integrated into an interacting network to produce various specific differentiatied functions. To elucidate the mechanisms of such interactions in the differentiation of T lymphocyte, a systematic study was carried out to characterize a liquid suspension culture system for T progenitor cells from human peripheral blood or bone marrow. T progenitor cells were assayed either by their membrane properties or by their ability to form colonies in semisolid media. T lymphocyte growth stimulators (TL-GS) were isolated from phytohemagglutin (PHA)-stimulated human T lymphocyte conditioned medium. TL-GS were capable of selectively supporting growth for four months or longer of T progenitor cells. This system should facilitate the study of cell-factor interactions mediating the proliferation and differentiation of T lymphocytes.


Potentiation of responses to monoamines by antidepressants after destruction of monoamine afferents. 1 Stereotaxic lesioning and microiontophoretic techniques were used to study the effects of lesions of the medial forebrain bundle (MFB) on the potentiation by antidepressant drugs of responses to monoamines of cortical neurones.2 Active uptake of noradrenaline (NA) and 5 hydroxytryptamine (5-HT) by synaptosomes from the motor and somatosensory cortex was reduced to approximately 20%, 10 to 14 days following lesion of the MFB in rats.3 Unilateral lesions of the MFB caused changes in responsiveness of neurones to NA and 5-HT, applied by iontophoresis, in the cortex ipsilateral to the lesion. Excitatory responses to both amines were observed less frequently and depression was the predominant response. Excitatory responses on the lesioned side were significantly smaller than on the unlesioned side, but the size of depressant responses was unaltered.4 Viloxazine strongly potentiated responses of cortical neurones to NA and 5-HT on both sides of the brain of MFB-lesioned rats. There were no significant differences in the potentiation of responses to monoamines on the lesioned or unlesioned sides of the brain.5 Desipramine potentiated responses to NA of neurones in the cortex ipsilateral to MFB lesions.6 Chlorimipramine potentiated responses to 5-HT of neurones in the cortex ipsilateral to MFB lesions.7 It is concluded that antidepressants can potentiate responses to monoamines despite a profound reduction in presynaptic terminals. The potentiation is unlikely to be the result of blockade of monoamine uptake into presynaptic terminals, and is probably a postsynaptic effect of the antidepressant drugs.


Bovine lymphocytes: erythrocyte rosettes in normal, lymphomatous and corticosteroid-treated cattle. Spontaneous erythrocyte rosettes, antibody-complement rosettes and nonrosetting cells were enumerated for peripheral blood lymphocytes of normal adult, lymphomatous adult and immature cattle as well as for peripheral blood lymphocytes of adult cows both before and after injection of corticosteroids. Calf thymic lymphocytes were also examined for rosette formation. Results indicate significant reduction in peripheral blood lymphocyte-erythrocyte rosettes and nonrosetting cells in tumour-bearing cows with a simultaneous elevation in percent antibody-complement rosettes. Calf thymus had a significantly greater percent erythrocyte rosettes than did peripheral blood lymphocytes from the same individuals. Corticosteroid injection reduced peripheral blood lymphocytes without altering proportion of cells as erythrocyte rosettes, antibody-complement rosettes or nonrosetting cells.


Sensitivity of hypothalamic sites to salicylate and prostaglandin. This study was designed to determine the dose of salicylate necessary to produce substantial antipyresis, and to determine the relationship between the response to salicylate and prostaglandin infused into the same region of the preoptic area of the rabbit. The effect of preoptic infusions of three doses of sodium salicylate, or a control solution, on the fever produced by an intravenous injection of endogenous pyrogen was measured. The pyrogenic response to prostaglandin E1 injected into the same preoptic sites in the same rabbits was also monitored. The results showed that the 50 microgram/microL per hour dose of salicylate did not produce significant antipyresis but that the 100 and 200 microgram/microL per hour doses did. The results also showed a significant correlation between the magnitude of fever produced by prostaglandin E1 and the magnitude of antipyresis produced by sodium salicylate at a particular site. Those sites at which infusion of salicylate produced the most effective antipyresis were also the ones at which prostaglandin E1 produced the largest fevers.


High dose methotrexate with and without BCG therapy in advanced head and neck malignancy. Twenty-three patients with advanced recurrent head and neck carcinoma were randomized to receive either high dose methotrexate with calcium leucovorin rescue (HDMTX) or HDMTX in combination with bacilli Calmette Guerin (HDMTX/BCG). An additional eight patients were treated with escalating doses of HDMTX ranging from 1 to 7 g of methotrexate. Of 12 patients receiving HDMTX, one complete response and two partial responses were noted. Of 11 patients in the HDMTX/BCG group, one complete response and two partial responses were observed. Only one partial response was noted in eight patients receiving escalating doses of the drug. Responses were brief and no significant difference in response duration was seen in any particular group. Toxicities in all groups were tolerable. BCG did not improve response rate, median duration of response, or median survival in these patients. Reported experiences with high dose methotrexate have been reviewed and again, responses to "high dose methotrexate" were found to be of brief duration. Despite acceptable toxicity, the brief duration of response and cost of such therapy raises serious question on the usefulness of chemoimmunotherapy utilizing high dose methotrexate with leucovorin rescue and BCG in the management of advanced recurrent carcinomas of the head and neck region.


Stimulation of resistance to tumor growth of athymic nude mice pretreated by combined local hyperthermia and X-irradiation. Host resistance to tumor growth was studied in athymic nude mice of C57BL background. Animals were pretreated in the left hind leg by local hyperthermia, local X-irradiation, or combined local hyperthermia and X-irradiation. Twenty-four hr posttreatment, the animals were inoculated with the metastatic Lewis lung carcinoma tumor. Half of the animals in each group were inoculated in the pretreated leg and animals of the other half of the group were inoculated in the contralateral untreated leg. An increase of 30 to 45% in life span was achieved in normal and nude mice pretreated by combined local hyperthermia and irradiation. The increase in life span was similar in animals inoculated in the pretreated leg or in the untreated contralateral leg. These results indicate that T-lymphocytes are not involved in the protection against tumor growth.


Inhibition of the lectin-induced mitogenic response of thymocytes by glycolipids. Exogenous gangliosides at concentrations found in serum inhibit the concanavalin A- (Con A) induced mitogenic response of mouse thymocytes. Of four gangliosides tested, the trisialoganglioside, GT1, was the most potent inhibitor. Ceramides, cerebrosides, and sialic acid were not inhibitory at any concentration tested. The inhibition by gangliosides was not due to interference with Con A binding as shown by direct binding studies with [3H]acetyl-Con A nor was it due to a nonspecific killing effect. Thymocytes exposed to a ganglioside concentration 5 times that required to inhibit mitogenesis were still capable of excluding trypan blue up to 44 hr after ganglioside addition. Furthermore, ganglioside inhibition could be reversed by washing the cells 4 hr after addition of the glycolipid. A productive interaction with Con A occurs in the presence of ganglioside as shown by a Con A-induced increase in carbohydrate metabolism. However, uridine and thymidine incorporation are inhibited by the presence of ganglioside. Complete inhibition could be achieved if the glycolipid were added as late as 24 to 28 hr after the Con A in a 48-hr mitogenic assay. The results are discussed in light of recent findings that elevated levels of gangliosides are found in in the sera of tumor-bearing animals, and it is suggested that gangliosides shed by tumor cells could be involved in the generalized immunosuppression observed in such animals.


Dose-dependent adjuvant effects of Bacillus Calmette-Guérin on tumor immunity in Lewis rats. The study was undertaken of the ability of Bacillus Calmette-Guérin (BCG), used in combination with a live tumor cell vaccine, to potentiate systemic antitumor immunity in rats. BCG was administered in two injections, with the first one given i.v. and the second one given intradermally mixed with the tumor cell vaccine 12 days later at the time of implant of an s.c. tumor, which served to monitor antitumor immunity. Both these BCG injections were necessary to obtain maximal protection measured in terms of increased survival rates of the rats and of decreased tumor growth rates. The dose of BCG in both the first and second injections was critical for optimal protection, since low doses (125 to 250 micrograms) afforded protection, while higher doses (over 1500 micrograms) decreased or abolished the protective effect. These results strongly suggest that BCG, only if administered under the appropriate conditions, is able to potentiate systemic tumor immunity and to provide a significant level of protection for a tumor-bearing animal.


Erythroid leukemia induced by Friend lymphatic leukemia virus in T-cell-depleted mice. BALB/c mice depleted of T-cells by thymectomy at 3 to 5 days of age and by treatment with antithymocyte serum were inoculated with the lymphatic leukemia virus derived from Friend virus. After a long latent period, these animals developed erythroid leukemia. In contrast, intact control mice inoculated with Friend virus-associated lymphatic leukemia virus developed typical thymic (T-cell) lymphomas. Cell-free virus prepared from leukemic T-cell-depleted animals induced lymphoid, myeloid, and erythroid leukemias in intact mice. The erythroid leukemia-inducing virus differed from the spleen focus-forming component of Friend virus in its long latent period (88 to 225 days) and in its inability to induce spleen foci. End-point dilution experiments suggested that a hitherto undescribed component of the Friend virus complex might be responsible for these late-appearing erythroid leukemias.


Serum inhibitor activity of granulocyte-macrophage colony formation in patients with cancer. The serum inhibitor activities of granulocyte-macrophage colony formation were evaluated by the in vitro culture technique in 60 patients with cancer and control subjects including 24 normal adults and 27 patients with a variety of nonneoplastic disorders. The inhibitor activity in cancer patients (mean, 59%) was significantly higher (p less than 0.001) than was that in normal adults (mean, 31%) and patients with nonneoplastic diseases (mean 36%). There was no difference in the inhibitor activity between the latter two groups of subjects. There was no correlation between the serum inhibitor activity in cancer patients and the histological type or primary site of tumor, the estimated duration of extent of disease, and serum albumin levels. Preliminary observations indicated that the inhibitor activity may be associated with serum lipoproteins. There was no significant difference in serum colony-stimulating activity among cancer patients, normal subjects, and patients with nonneoplastic diseases.


Relationship between the chemical structure and anti-tumour activity of glucans prepared from Grifora umbellata. Glucans from Grifora umbellata and their enzyme-treated fractions have been tested for antitumour activity against subcutaneously implanted Sarcoma 180 (solid type). The results indicate that the basic common unit of the glucans is of primary importance for the antitumour activity, which is also influenced by the type of sugar linkage, length of branch, branching frequency, molecular size, and molecular conformation.


Recovery of viruses from field samples of raw, digested, and lagoon-dried sludges. In a 22-month study, viruses were detected in 84% (62/74) of raw, 53% (19/36) of anaerobically digested, and 39% (11/28) of lagoon-dried sludge samples. Lagoon sludge contained detectable viruses (reovirus and enterovirus groups) even after 8 months of retention. Because of such prolonged virus survival in sludge, care must be taken in its disposal or utilization.


Disasters and public health.

Disasters and public health. Studies on the health effects of disasters have shown that epidemiological indices can be of value in planning preventive and relief measures and in evaluating their effectiveness. Mortality rates naturally vary considerably, but in earthquakes, for example, the number of deaths per 100 houses destroyed can give an indication of the adequacy of building techniques. Age-specific mortality rates can help to identify particularly vulnerable groups and perhaps indicate what form of education would be valuable. Except in earthquakes, the number of casualties after a disaster is usually low in relation to the number of deaths, and study of the distribution and types of lesions would help in planning the amounts and types of relief supplies and personnel required. Disasters also affect the general level of morbidity in a district because of either interruption of normal health care services or of spraying or other disease control measures. Mental health and nutrition following disasters are particular problems that require further investigation. Study of all these features of disasters has been handicapped by a lack of data, particularly concerning the health situation immediately after the impact. The provision of surveillance teams in disaster-prone areas would appear to be a field in which international cooperation could yield immense benefits.


Complement (C3), nutrition, and infection. Complement (C(3)) was determined and related to various parameters of nutritional status and past infectious disease experience in a group of 53 rural preschool children in North India. Mean complement level was 25% lower than in an age-matched European reference population. Low complement (C(3)) levels were associated mainly with children who were both stunted and wasted, as well as with those who had experienced frequent purulent skin infections in the past.


Adherence of wild-type and mutant strains of Vibrio cholerae to normal and immune intestinal tissue. Adherence of some wild-type and mutant strains of Vibrio cholerae was studied and the relation between adherence, motility, multiplication, and virulence was examined. Vibrios adhered readily to freshly isolated tissue segments of rabbit intestine at 37 degrees C. The number of vibrios adhering was dependent on the concentration of bacteria to which the tissue was exposed. Adherence was markedly reduced by pretreatment with chloramphenicol and also when intestinal tissue was taken from parenterally or orally immunized rabbits. Non-motile or feebly motile strains were unable to adhere. One motile strain was also found to adhere poorly. The adherence of non-motile or poorly adhering strains was not affected by chloramphenicol. Non-motile, poorly adhering, or slow-growing strains behaved as attenuated strains, suggesting the role of motility, adherence, and multiplication in the virulence of V. cholerae.


Adverse reactions to rifampicin.

Adverse reactions to rifampicin. This summary of adverse reactions to rifampicin has been prepared with the intention that it will be made available to all those involved in the administration of rifampicin in tuberculosis and leprosy control programmes. The reactions covered comprise those to both daily and intermittent administration, namely cutaneous and gastrointestinal reactions, hepatitis, and thrombocytopenic purpura, and those to intermittent administration only, namely "flu" syndrome, shock, shortness of breath, haemolytic anaemia, and renal failure.


Protein and energy requirements: a joint FAO/WHO memorandum. Since the publication in 1973 of the report of a Joint FAO/WHO Ad Hoc Expert Committee on protein and energy requirements, some investigations have indicated that the safe levels of protein intake recommended in that report may be too low. This Memorandum reviews the current situation and makes further recommendations where necessary.


The Mamprobi Survey--a screening survey for cardiovascular disease and risk factors in Africa: methodology and validity. The Mamprobi Survey is a cardiovascular disease prevalence sample survey in an African community in Ghana. This preliminary paper describes its methodology and validity. Response rate corrected for migration from the area was 73%. Subsequent sampling of non-respondents revealed only trivial reasons for non-attendance and only minor differences in health status, suggesting that estimates of disease prevalence by the survey were likely to be accurate.


Blood pressure and heart murmurs in a rural population in the United Republic of Tanzania. Hypertension, congestive heart failure, and valvular heart disease are frequently seen among hospital inpatients in the United Republic of Tanzania. A population survey was therefore carried out to determine the prevalence of hypertension and cardiac murmurs in a random sample of people aged 25-64 years living in an undeveloped rural area. Standard cardiovascular survey methods as recommended by WHO were used. Only mean systolic blood pressure in women increased with age; even so, the difference in mean levels between those aged 25-34 and 55-64 years was only about 1.6 kPa (12 mmHg). Hypertension was found to be uncommon, only 2% of subjects having blood pressures >/= 21.3/ 12.7 kPa (>/= 160/95 mmHg). By means of multiple regression analysis, less than 10% of the variance in blood pressure levels could be explained by age and anthropometric measurements. Murmurs of grade 2 or more were detected in 17% of the men and 22% of the women, being most commonly heard at the apex (54%) and the left lower border of the sternum (31%). Mitral valve diastolic murmurs were heard in 4 of 275 women and these were asymptomatic. The cause of the high prevalence of systolic murmurs is unknown.


The effect of cyproheptadine on the release of corticotrophin releasing factor. The effect of cyproheptadine was tested on the neurotransmitter-induced release of corticotrophin releasing factor (CRF) from the rat hypothalamus in vitro. It was found that cyproheptadine inhibited both acetylcholine and 5-hydroxytryptamine-induced release of CRF. Cyproheptadine did not interfere with the ACTH releasing ability of CRF. These results suggest that cyproheptadine reduces the high circulating levels of ACTH in some patients suffering from Cushing's disease and Nelson's syndrome by inhibiting CRF secretion.


Regulatory T cells in the humoral response of protein deficient mice. Cell suspensions from the spleen or thymus of mice fed normally or mice that were protein deficient were injected into mice from each dietary group and also syngeneic nudes. Antigen, polyvinyl pyrrolidone (PVP), was injected at the stage of cell transfer and the antibody titres of the recipient animals were compared with those of control animals given only antigen. The regime was repeated using cell suspensions from donor animals which had been primed with antigen. These experiments showed that spleen cells were suppressive only when transferred from deficient to normal mice. Thymocytes generally lacked suppressive effects, except when given to irradiated mice also injected with "normal" spleen cells. However, thymocytes from deficient mice were marginally enhancing in nude mice, deficient mice and older "normals". To explain these results, it is suggested that responses to PVP are determined by distinct "suppressor-inducing" and "suppressor" T cells which act via helper T cells. The latter probably affect B cells directly and largely influence IgG production. It also appears likely that the ratio of helper to suppressor (inducer and effector) T cells is increased by protein deficiency.


Immunosuppressive therapy in collagen vascular diseases. Over the past ten to fifteen years cytotoxic drugs have gradually been added to the therapeutic armamentarium of physicians other than oncologists, particularly dermatologists. They are being used to treat nonmalignant cutaneous diseases such as pemphigus vulgaris, bullous pemphigoid, and psoriasis. The rationale for their use in these diseases is conjectural, yet those dermatologists who use them feel strongly not only that cytotoxic drugs are effective, but that when used properly, they are relatively safe. The immunosuppressive activity of cytotoxic drugs has been accepted and widely acclaimed in immunology, renology, and transplant medicine. However, their usefulness in two autoimmune diseases frequently managed by dermatologists is widely disputed. In this short discussion the rationale for the use of cytotoxic agents and evidence for their effectiveness when used appropriately in progressive systemic sclerosis and systemic lupus erythematosus is presented.


Abnormal blood vessels in the gastric antrum: a cause of upper-gastrointestinal bleeding. Three patients who bled from curious vascular lesions of the gastric antrum are described. Each presented with an iron-deficiency anemia. Histological examination in two of the patients demonstrated numerous ectatic submucosal vessels in the antrum, the appearances being somewhat similar to angiodysplasia of the colon. The gastric lesions were not shown by barium meal examination or angiography but gave characteristic appearances on endoscopy. We believe that Billroth I partial gastrectomy is the treatment of choice for this condition.


Continuous peritoneal dialysis as treatment of acute experimental pancreatitis in the rat. I. Effect on length and rate of survival. Continuous peritoneal dialysis significantly prolonged mean length of survival and reduced lethality rate of taurocholate-induced pancreatitis in the rat. The effect was improved by compensating protein loss due to pancreatitis and dialysis treatment. The beneficial effect of intravenous albumin treatment was enhanced when combined with dialysis treatment. Using hypothermic dialysate or adding aprotinin intraperitoneally had no additional effect.


Thyroid activity in early weaned and suckling infants and their lactating mothers. The activity of thyroid gland was estimated in a group of lactating mothers and their suckling infants as well as in a group of early weaned infants. In both groups of infants the same level of thyroxine and triiodothyronine was found, but it was higher than that in mothers. The binding properties of specific plasma proteins and free thyroxine index were the same in both groups of infants. The level of TSH in serum of suckling infants (4.7 +/- 0.5 microunits ml-1) was significantly higher (P less than 0.01) than that in weaned infants (3.0 +/- 0.3 microunits ml-1). The level in mothers (4.0 +/- 0.3 microunits ml-1) did not differ significantly from that in both groups of infants. A positive correlation was found between the level of TSH in lactating mothers and their suckling infants (r = +0.494, P less than 0.05). The data suggest that the regulation of thyroid activity in infants may be affected by suckling.


Serum prolactin and estrogen pattern in human gestation. In a group of 17 normal women serum levels of fetoplacental hormones (estradiol, progesterone and human placental lactogen) and of prolactin were measured serially from the 6th week to the end of pregnancy. The levels of these hormones increased gradually until the term. On the basis of these observations it may be concluded that no statistical evidence may be found on any direct effect of estradiol on prolactin release. These results seem to confirm some earlier data that estrogens may be less marked stimulators of prolactin secretion in man than in animals.


Regional net uptake of 14C-glucose by rat brain under the influence of corticosterone. Fifteen seconds after intracarotid injection of either 14C-glucose or tritiated water in adrenalectomized rats, the net uptake of the respective tracer by 18 brain regions and by the anterior pituitary was measured. Corticosterone added to the injection solution (1 or 100 micrograms ml-1; 0.2 ml per animal) caused a dose-dependent decrease of net uptake of 14C-glucose in twelve regions. Compared to the net uptake of tritiated water which was used as a measure of relative blood flow, it suggests that this effect, at least partially, is due to a decreased blood-brain barrier permeability to 14C-glucose. Furthermore, the regional net uptake of 14C-glucose was estimated in rats with different endogenous corticosterone levels but injected with an identical solution in each case. Statistically significant differences could be observed between adrenalectomized and restrained animals in three brain regions.


Changes of LH, TSH, GH, FSH and PRL in pituitaries and sera of rats after thyroidectomy and thyroxine treatment as studied by radioimmunoassay and disc electrophoresis. Rat pituitary hormones (LH, TSH, GH, FSH and PRL) were located in polyacrylamide gels after the separation of rat pituitary homogenate with the aid of electrophoresis. Furthermore, the incorporation of 3H-glucosamine and 14C-leucine into various protein fractions of incubation media and pituitaries incubated for 6 h in vitro, homogenized and then subjected to disc electrophoresis was measured in six groups of rats: 1. control; 2. two weeks after thyroidectomy (Tx); 3.--6. two weeks after thyroidectomy and injected 20 micrograms L-thyroxine (T4) i.p. per animal at 6, 12, 24 and 48 h before sacrifice, respectively. A decrease of 14C-leucine incorporation into GH and PRL after thyroidectomy was found which was improved by T4 treatment. Moreover, an increase of 3H-glucosamine and 14C-leucine incorporation into TSH zone and origin zone was observed, the former presumably representing the extracted TSH and the latter consisting of unextracted portion of TSH, other hormones and unidentified proteins. Such increase was significantly less after T4 treatment. Finally, changes of radioimmunoassayable LH, TSH, GH, FSH and PRL in pituitaries and sera of analogous groups of rats, but consisting of another animals were measured. The content of TSH in the pituitary slightly increased after Tx, but increased further after T4 treatment. In contrast, the content of all other hormones in the pituitary decreased after Tx, while T4 treatment resulted in a stepwise increase. In plasma, a significant decrease of GH and PRL after Tx was found with no remarkable changes after T4 treatment. The level of LH and FSH was unchanged, while that of TSH increased significantly after Tx and sharply decreased to the original level as early as at 6 h after the injection of T4.


Maturation of 17 beta-estradiol binding protein in the hypothalamus and anterior pituitary of male rats. Levels of estrogen binding proteins in the cytosol of hypothalamic and pituitary tissue of male rats at different ages were estimated. Two classes of estrogen binding sites were detected in 13 and 20 days old animals. The number of high affinity estrogen binding sites (K = ca. 2 x 10(-10) mol) of the hypothalamus was slightly larger in 13 days old animals, then decreased to constant levels at the age of 20 days and no changes were observed thereafter. Levels of low affinity binding sites of the hypothalamus (K = ca. 5 x 10(-9) mol) decreased with age and were no longer detectable in 30 days old animals. Similarly, a decrease of low affinity estrogen binding sites with age was recorded for pituitary cytosol samples and this class of receptor sites was no longer observable in 30 days old male rat. At 13 days high levels of high affinity 17 beta-estradiol binding protein was registered and minimal numbers of binding sites were found at 20, 30 and 40 days. Thereafter, the levels remained constant until 100 days and were similar to values observed in the 13 days old male animals. Apparent affinity constants of two classes of binding sites in hypothalamus and pituitary were similar...


Treatment of ringworm in horses with natamycin. A suspension based on the antibiotic, natamycin, was applied by sponging to 83 horses of various breeds and ages with signs of clinical ringworm. A number of different causative agents were involved of which Trichophyton equinum was the most common. Treatment successfully eliminated the disease within 4 weeks. After treatment the recovered animals did not show any evidence of re-infection for up to 6 months. The mycological clearance rate was 97 per cent and apart from the efficacy against ringworm, the preparation had the advantage of being non-irritant and odourless. It was also useful for treating the surroundings of the animals.


The proliferative states of density subpopulations of granulocyte-macrophage progenitor cells. Possible variation in proliferative state among subpopulations of myelopoietic progenitor cells of mouse bone marrow (CFU-c), which form in vitro colonies of granulocytes and/or macrophages, was investigated by estimation of the percentage in S phase of the cell cycle. Subpopulations of CFU-c, obtained by separation of femoral marrow cells on continuous albumin density gradients, were detected by culture in agar with different types of colony stimulating factor (CSF). The percentage of CFU-c in S phase, detected with mouse lung conditioned medium (CSFMLCM), averaged 17%. This was significantly lower than the 41% which was found when an extract of human urine (CSFHU) was used. This result was obtained with unfractionated marrow cells both by in vitro suicide with tritiated thymidine and by in vivo administration of hydroxyurea. There were different CFU-c responses to CSF, on the basis of their density distributions. Those responding to CSFMLCM had a low density disposition whereas the CSFHU responders had a high density disposition. The administration of hydroxyurea resulted in an alteration in the density distribution which indicated that a larger proportion of high density CFU-c were in S phase. The results indicate that CFU-c responding to different types of CSF differ in buoyant density and proliferative state.


Stimulation of alkaline secretion in amphibian-isolated gastric mucosa by 16,16-dimethyl PGE2 and PGF2 alpha. A proposed explanation for some of the cytoprotective actions of prostaglandins. The mechanism of the gastric cytoprotective action of prostaglandins is unknown but seems to be unrelated to inhibition of acid secretion. In the present study, effects of the prostaglandins, 16,16-dimethyl E2 and F2 alpha on H+ and HCO-3 secretion and electrical properties in amphibian-isolated gastric mucosa were studied. Spontaneous net secretion in fundic mucosa from Rana temporaria and Necturus was acid, whereas Necturus antrum secreted only HCO-3. The histamine H2-receptor antagonist, metiamide (10(-3) M), was used to inhibit acid secretion for studies on fundic alkalinization. Nutrient side administration of 16,16-dimethyl E2 (10(-6) M) for 60 min inhibited H+ secretion and stimulated HCO-3 secretion in Rana temporaria fundus. The drug (10(-5) M) also stimulated antral alkalinization. There was a dose-related increase in HCO-3 secretion in Necturus fundus after administration of F2 alpha (10(-5)-10(-4) M), but this drug had no significant effect on H+ secretion. Inhibition of acid secretion by 16,16-dimethyl E2 was associated with an increase in potential difference (PD), but there was no change in electrical resistance. Neither of the prostaglandins affected PD or resistance in alkaline-secreting tissues. Previous work has suggested that gastric HCO-3 secretion has a physiologic role in protecting the mucosal surface. The ability of prostaglandins to stimulate alkaline secretion may contribute to the cytoprotective action of these drugs in the stomach.


Hemobilia secondary to metastatic liver disease. Hemobilia has previously been reported only in association with primary hepatic tumors. A patient with metastatic liver disease is described who presented with melena, abdominal pain, and jaundice. Bleeding from the ampullary papilla was observed at endoscopy. Jaundice resulted from biliary obstruction by blood clots containing foci of tumor cells identical to those of the hemorrhagic hepatic tumor nodules. Hemobilia from metastatic liver disease may occur more commonly than reported.


Prevalence and causes of anemia in elderly hospitalized patients. The prevalence and causes of anemia have been studied in 104 patients over 60 years of age admitted to a general medical ward in Jerusalem. In males and females, mean hemoglobin levels were about 1 g less than in the corresponding groups of healthy younger controls. A primary nutritional anemia could not be implicated in any of the 15 patients with hemoglobins below 11 g/dl. The most important causes of anemia were chronic renal failure, metastatic carcinoma, gastrointestinal bleeding, and infection. Conversely, in diseases with no adverse effect on erythropoiesis such as chronic ischemic heart disease, hypertension and diabetes, hemoglobin levels were equal to those of the younger controls. These findings indicate that although diminished serum iron and RBC folate levels may occasionally be found in elderly subjects, nutritional deficiency is seldom responsible for anemia in this age group in Israel- and anemia when present is often the manifestation of a chronic underlying disease.


Treatment of osteomalacia associated with primary biliary cirrhosis with parenteral vitamin D2 or oral 25-hydroxyvitamin D3. The histological and biochemical response of osteomalacia has been studied in four patients with primary biliary cirrhosis, who were treated with oral 25-hydroxyvitamin D3, 50 microgram daily, or intramuscular vitamin D2, 150,000 units once weekly, for five to 12 months. All patients showed complete histological healing of osteomalacia, despite rapidly deteriorating liver function in three. Plasma 25-hydroxyvitamin D concentrations were low in all patients before treatment, but became normal during either vitamin therapy. Serum calcium and phosphate levels, and urinary calcium excretion were not always reliable in predicting the histological response to treatment. Serum alkaline phosphatase activity decreased in all patients during vitamin D therapy. We conclude that both high-dose parenteral vitamin D2 and oral 25-hydroxyvitamin D3 may be effective in healing osteomalacia associated with primary biliary cirrhosis. Measurement of plasma 25-hydroxyvitamin D levels during vitamin D therapy provides useful information about 25-hydroxylation of the parent vitamin and intestinal absorption of orally administered 25-hydroxyvitamin D3.


Experimental results of the use of flavofosfolipol in dairy cattle. In a field trial carried out on a farm with about 100 dairy cows, half of the animals were treated orally with 45 mg flavofosfolipol per animal daily for 370 days, while the other half were untreated controls. The administration of the flavofosfolipol did not produce any residues in the milk. Body functions and fertility were not affected. Milk production was increased, although not with statistical significance. The qualitative characteristics of the milk and its cheese-making properties were normal. The casein content was increased by 6.58% over that of the controls, and thus was statistically significant. There was a statistically significant decrease in the mean cell content of the milk. The high negative correlation between the casein level and the cell content of the milk suggests that an improvement in the function of the mammary parenchyma could be responsible for the higher casein content. This improvement in function could also be due to a favourable effect of the antibiotic, still to be clarified, on the ruminal microflora. In economic terms the use of flavofosfolipol in dairy cattle seems to be of considerable interest.


The prevalence of chronic diseases in children in out-hospital care in Finland. The records of public health nurses have been used for an estimate of the prevalence of children in domestic care and suffering from various kinds of chronic diseases. This estimate provided a basis for computation of the number of chronically ill children in out-hospital care in Finland. The research was carried out as a sample research and this inquiry resulted in the information of the anamnesis of 12,721 chronic children under 16 years of age taken care of at home. We have counted as chronics those children whose disease is lingering either due to its mechanism of origin or to its nature or known to be such from experience. The total prevalence was 53% of the child population in Finland which corresponds to 59,000 chronically sick children. The geographical distributions of the groups of the diseases were not quite alike in the different parts in our land. The greater prevalences were found on the other hand in Northern Finland and in the wide archipelago of Southwestern Finland. The most common types of the chronic diseases of children were found to be those of sense organs (the total prevalence was 18%). The prevalence of allergic diseases varies between 6--12% and the disease group of endocrinic glands 1.0--3.4%. The prevalence of the neurological diseases was 2.3% and the biggest group consists of the convulsive. The prevalence of the other groups of diseases were: the psychiatric diseases 2.2%, the urological diseases 1.4% and the hematological diseases 0.8%.


Heat-induced thermal resistance and its relationship to lysosomal response. Two separate effects of hyperthermia on mouse splenic lysosomes have been reported, dependent on the severity of the treatment. Heating to temperatures below 42.5 degrees C causes a transient increase in lysosomal acid phosphatase activity which can be correlated with the ability of moderate hyperthermia to potentiate X-ray damage. Heating to temperatures above 42.5 degrees C results in an immediate increase in lysosomal membrane permeability which may be involved in tissue necrosis. By giving a priming heat treatment at 41.8 degrees C, induced thermal resistance was demonstrated for the lysosomal membrane effect, but not for the enzyme activation. The degree of induced thermal resistance observed is similar to that reported for the cell-killing effect of heat on tissues in vivo and cells in vitro and occurs over a similar time course. The relevance of these results to the understanding of fractionated hyperthermia in cancer therapy is discussed.


'Repair' of fast-neutron and x-ray-induced damage to the permeabilities of red blood cells to sodium and potassium ions and its promotion by ghosts. Damage to the permeability of red blood cells to Na+ and K+ caused by irradiation with fast neutrons or X-rays was investigated at different post-irradiation incubation temperatures. The extent of Na+ uptake and K+ loss by the cells after either radiation was higher at 4 degrees C than at 37 degrees C, but the extent of 'repair' of the damage caused by fast neutrons was lower than that caused by X-rays. The latter 'repair' was promoted by the addition of ghosts, but the former was not. On the other hand neither 'repair' process was influenced by haemolysates from which ghosts had been removed.


The ultrastructure of mouse testicular interstitial tissue containing plutonium-239 and its significance in explaining the observed distribution of plutonium in the testis. The technique of autoradiography with Araldite-embedded sections was used to study the distribution of 239Pu in mouse testis at various times post-injection. Adjacent sections were examined with both the light microscope and electron microscope. The autoradiographs showed that from 1 week to 3 months postinjection, most 239Pu in located in interstitial tissue. The major change in distribution observed was that the early diffuse deposit in interstitial tissue is concentrated in macrophages with increasing time post-injection. This is a real change of distribution as the amount of 239Pu in mouse testis remains constant from 1 week to 3 months post-injection. Study of the ultrastructure of interstitial tissue indicated that the accumulation of 239Pu in macrophages may be brought about in two ways. First, there may be phagocytosis of dead cells containing 239Pu. Second, 239Pu may follow the transfer of waste products of hormone synthesis from Leydig cells into macrophages. The significance of these observations is discussed with regard to the deposition of 239Pu in human testis.


A gold foil electrode: extending the horizons for clinical electroretinography. A gold foil ERG electrode is described. The device is inexpensive and simple to fabricate. Since it is hooked over the lower lid and makes minimal touch contact with the inferior limbal area, it can be used in circumstances which require prolonged testing of retinal function or in eyes with corneal pathology. Because the optics of the eye are not compromised, it is possible, with the use of appropriate stimuli and response-averaging techniques, to record local EFGs from relatively small retinal areas.


Vision threshold profiles in X-linked retinitis pigmentosa. Absolute thresholds for blue-green and red stimuli were measured along the horizontal and vertical meridans in two patients with X-linked retinitis pigmentosa. From these data, we deduced that cones mediate detection of both stimuli in the central 10 degrees, there is a ring scotoma in the mid-periphery, and in the far periphery rods mediate detection of both stimuli. Conclusions drawn from the psychophysical measures about rod and cone function across the retina are in point-by-point agreement with the data of a recent electron microscopic study by Szamier et al. on the retina of a 24-year-old X-linked retinitis pigmentosa patient.


Natural killer activity in patients with acute myelocytic leukemia. The natural killer activity of isolated mononuclear cell populations of acute myelocytic leukemia (AML) patients in remission and relapse was compared with that of mononuclear cells obtained from normal subjects. The target cells consisted of 51Cr-labeled blast cells of the K-562 cell line, which was originally obtained from a patient with chronic myelocytic leukemia in blast crisis. The natural killer activity of lymphocytes from AML patients in remission was similar to or higher than that of normal subjects. A marked depression in this function was associated with relapse, as well as with heavy combined chemotherapy. It is concluded that natural killer activity assessed in vitro is an accurate indicator of the clinical stage of AML patients.


[The importance of selective angiography in colonic diverticulosis surgery]. The diverticular disease of the colon is one of the most frequent causes of massive bleeding of the large bowel. The results of emergency operations without localisation of the bleeding are disappointing. The bleeding point can be localised by selective angiography, and this renders possible the most favourable surgical procedure as shown by the case report of a high risk patient.


Thiamphenicol in treatment of Haemophilus influenzae meningitis. 17 infants and children with pyogenic meningitis (14 Haemophilus influenzae, 2 Diplococcus pneumoniae, 1 Neisseria meningitidis) were treated with thiamphenicol, 100 mg/kg body weight/day in 4 doses i.v., as single drug. In the H. influenzae group 10 patients were cured, 4 had relapses of meningitis, 3 with documented subdural effusions. This group is compared with 14 children matched for age, initial leucocyte and CSF cell count treated with ampicillin: all of these were cured, 1 had a subdural effusion. Thiamphenicol concentrations were determined in the serum and CSF 2 h after administration. The mean serum levels were between 10-12 mcg/ml, the mean CSF levels varied from 5.4 mcg/ml at the beginning to 1-1.9 mcg/ml at the end of meningitis. The MIC of H. influenzae was 0.6-12 mcg/ml. A significant, acute, and dose related bone marrow toxicity of thiamphenicol could be documented, but was always rapidly fully reversible. We conclude that thiamphenicol cannot replace chloramphenicol in the treatment of pyogenic meningitis as single systemic antibiotic. Special indications for thiamphenicol in this disease are discussed.


Computer analysis of Feulgen hydrolysis kinetics. A least squares fit of Feulgen hydrolysis time curves to the Bateman function is performed using an especially adapted parameter transformation together with a standard conjugate gradients iteration procedure. The method has been applied to a large number of measured data, and the use and limits of the computer evaluation are discussed.


Antithyroglobulin (ATG) production by peripheral blood leukocytes in vitro. Antithyroglobulin is produced in vitro by pokeweed mitogen stimulation of peripheral blood lymphocytes from patients whose serum contains the autoantibody. Antithyroglobulin synthesis requires T lymphocyte help but is suppressed by larger numbers of T lymphocytes. T cells from both patients and normals perform both of these functions.


Studies on suppressor cell function in thyroid diseases. Suppressor cell function of peripheral mononuclear cells has been examined in patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer, as well as in healthy subjects. Suppressor cell function was assessed through two methods: 1) measurement of enhanced blastogenesis after 24-h preculture and 2) concanavalin A-inducible suppressor activity. The results from the two tests were coincident and indicate that suppressor cell function was significantly decreased in the Graves' disease population but not changed in either the Hashimoto's thyroiditis or the thyroid cancer groups compared to healthy controls. The impairment of suppressor cell function in the Graves' disease population was still observed when patients became euthyroid by treatment with antithyroid drugs, although the treated patients had improved suppressor cell function compared to untreated patients (P = NS). Low activity of suppressor cell function in the Graves' disease population might be a constitutional character based on an inherited abnormality specific for the disease population.


Pseudocoagulase activity of staphylococci. A total of 245 strains of staphylococci isolated from various pathological specimens derived from cases of human infections was tested for staphylocoagulase activity. Test systems employing normal citrated rabbit plasma and the same substrate supplemented with inhibitors of thrombin and proteolytic enzymes (but not influencing the staphylocoagulase activity) were used for testing suspensions of bacteria and cell-free culture supernatants. A total of 237 strains clotted normal rabbit plasma; however, addition of Trasylol and heparin resulted in positive results in 222 strains, whereas plasma supplemented with Trasylol and hirudin was coagulated definitely by only 173 strains. It is postulated that proteolytic enzymes of staphylococci interfere with staphylocoagulase-induced clotting and may simulate coagulase-positive activity of staphylococci. To avoid such false results, a test system for detection of staphylocoagulase should include proteolytic enzyme inhibitors. Possible mechanisms of these findings are discussed.


Recovery of Haemophilus influenzae from twenty-three blood culture media. Haemophilus influenzae is an important agent of bacteremia and has fastidious growth requirements. The purpose of this investigation was to determine the ability of commercial blood culture media to support the growth of this fastidious microorganism. Twenty-three types of blood culture media were inoculated with individual suspensions of eight strains of H. influenzae in the presence or absence of an erythrocyte-serum mixture. The rates of recovery of the H. influenzae strains from the various types of blood culture media were compared. The results demonstrated that the type of medium, the manufacturer, the erythrocyte-serum mixture, and the strain of H. influenzae influenced the recovery rates of H. influenzae. Optimal recovery of the strains of H. influenzae was obtained from brain heart infustion blood culture medium (GIBCO). Trypic soy broth (GIBCO) and supplemental peptone of Becton, Dickinson and Co. also were found to be superior to the remaining types of media tested for the recovery of H. influenzae.


Salient features of Haemophilus vaginalis. A total of 78 strains of Haemophilus vaginalis were examined for 104 features. All strains fermented dextrin, maltose, and starch. Additionally, more than 90% of the strains fermented galactose, glucose, and ribose. Arbutin, cellobiose, melibiose, rhamnose, and salicin were not fermented by any of these strains. None of the strains acidified any of 14 alcohols or alkalinized any of 25 organic salts and amides. More than 90% of the strains hemolyzed human blood agar and hydrolyzed hippurate. No strain hemolyzed sheep blood agar. A recommendation is included for those minimal features that best differentiate H. vaginalis from other oxidase- and catalase-negative, gram-negative organisms.


Haemophilus influenzae Type D meningitis. This report describes an unusual pathogen associated with post-traumatic meningitis. Haemophilus influenzae type D was isolated from both cerebrospinal fluid and blood of this patient with meningitis.


Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization. Booster immunization of normal individuals with soluble tetanus toxoid resulted in the ability of the individuals' peripheral blood lymphocytes to synthesize immunoglobulin (Ig)G antitetanus toxoid antibody in vitro when stimulated by pokeweed mitogen. The capacity for this in vitro antitetanus toxoid antibody response developed within 14 days after booster immunization, reached a peak between days 36--50, and disappeared by day 60. The inability of pokeweed mitogen to stimulate antitetanus toxoid antibody synthesis in vitro before booster immunization was not due to excess suppression by thymus-derived (T) lymphocytes but reflected insufficient numbers of functionally specific helper T lymphocytes and bone marrow-derived (B) lymphocytes. Antigen-specific T-lymphocyte suppression and decreased B-lymphocyte function were associated with the observed reduction of in vitro synthesis of antitetanus toxoid antibody from 20--60 days post-immunization. The in vitro kinetics of antitetanus toxoid antibody synthesis paralleled the synthesis of total IgG in that stimulation by pokeweed mitogen was required and that antibody secretion into the medium initiated by day 4 and increased through day 9.


Serum amyloid A: evidence for its origin in polymorphonuclear leukocytes. In this study the presence of an amyloid A, antigenically related material was determined in four subpopulations of human leukocytes. Monocytes, granulocytes, thymus-derived lymphocytes, and bone marrow-derived and null lymphocytes were isolated from the peripheral blood of five apparently normal subjects, two patients with secondary amyloidosis, three patients with acute infections, and seven patients with metastatic cancer. Mononuclear leukocytes, isolated from the interface of a Ficoll-Hypaque gradient, were separated into monocytes, thymus-derived lymphocytes, and bone marrow-derived plus null lymphocytes by glass adherence and depletion of sheep erythrocyte rosette-forming lymphocytes. Granulocytes were isolated by sedimentation in 2% methyl cellulose from the erythrocyte-rich pellet formed at the bottom of the Ficoll-Hypaque gradient. The four isolated leukocyte subpopulations were cultured and, at varying intervals, the amyloid A content of the culture medium and of sonicated, 2 x 10(6) cells was determined by radioimmunoassay. Our results indicated a 2-14 times greater amount of amyloid A-related material in the sonicated granulocytes compared with the individuals' serum amyloid A levels. The mononuclear subpopulations showed a low or negligible amyloid A content. The amount of amyloid A antigenic material was further found to increase in cultured granulocytes, reaching a peak value between the 16th and 30th h of culture. The granulocytes of only two out of eight individuals tested released amyloid A antigenically related material into the culture medium. This release was found to be blocked by the presence of colchicine, vincristine, puromycin, or cycloheximide in the culture medium. In contrast, only the presence of puromycin or cycloheximide was shown to significantly inhibit the intracellular increase of amyloid A in the cultured granulocytes. Thus, it appears that among the circulating blood cells, the granulocytes produce amyloid A antigenically related material and could release it under conditions that remain to be further defined.


Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin. Platelet Factor VIII-related antigen (VIIIR:Ag) represents a significant proportion of the total circulating VIIIR:Ag pool. However, its participation in the events of primary hemostasis has not been shown. We now report that platelet-contained VIIIR:Ag is released from platelets by collagen, ADP and thrombin. The concentrations of these agonists, required for VIIIR:Ag release, are the same or lower than those required for release of serotonin, lysosomal enzymes, or fibrinogen. This release has the features of an energy-dependent secretory response because it is blocked by the metabolic inhibitors, antimycin A and 2-deoxy-D-glucose. The electrophoretic characteristics of the VIIIR:Ag released by collagen and ADP are similar to those of plasma VIIIR:Ag. However, thrombin-released platelet VIIIR:Ag differs from that of plasma in that the less anodal forms are relatively depleted. These differences do not appear to be the result of proteolytic degradation of platelet-derived VIIIR:Ag, but may reflect interactions between specific molecular forms of VIIIR:Ag and the platelet membrane. These studies suggest mechanisms by which platelet-contained VIIIR:Ag may contribute to the primary events of hemostasis.


Mechanism of inhibition of porcine elastase by human alpha-1-antitrypsin. The interaction of the human plasma protein, alpha-1-antitrypsin, with porcine pancreatic elastase was studied by isolating and characterizing their reaction products. Native alpha-1-antitrypsin has a mass ratio (Mr) of 54,000, an amino-terminal glx, and a carboxy-terminal lys residue. The elastase used has an Mr of 26,400 and an amino-terminal val residue. When the two proteins are combined at inhibitor excess, two major products result. One of the products is a complex of the enzyme and inhibitor with amino-terminal ser and val residues, which indicates that a peptide has been removed from the amino-terminal end of the inhibitor. The second product is a modified form of alpha-1-antitrypsin with an Mr of 51,300, an aminoterminal glx residue and a carboxy-terminal thr-leu dipeptide. It has no inhibitory activity against elastase. The components of the isolated complex can be split at high pH in the presence of diisopropyl fluorophosphate, which results in a catalytically inactive enzyme with the same Mr and amino-terminal residue as the native enzyme, and a large fragment of alpha-1-antitrypsin (alpha-1-antitrypsin(*)). This fragment has an Mr of 50,100, an amino-terminal ser residue and a carboxy-terminal thr-leu dipeptide. Based on these data, the following hypothesis is proposed. Elastase can attack alpha-1-antitrypsin at either of two major sites. If it attacks first at the carboxy side of the thr-leu dipeptide, located in the carboxy-terminal portion of the inhibitor, the alpha-1-antitrypsin is cleaved into two fragments with loss of inhibitory activity and absence of complex formation. If, however, the elastase first attacks an x-ser bond near the amino-terminal end of the inhibitor, the elastase then reacts with alpha-1-antitrypsin at the same leu moiety to form a stable complex with complete inhibition of the enzyme.


Decreased circulating thymus-derived cells with receptors for the Fc portion of immunoglobulin G in systemic lupus erythematosus. Thymus-derived cells with receptors for the Fc portion of immunoglobulin G (Fcgamma+ T cells) have recently been found to have a suppressor function, a function that is decreased in systemic lupus erythematosus (SLE). Fcgamma+ T cells were found significantly diminished in 21 untreated SLE patients, particularly in the 7 patients who had active disease. Most Fcgamma+ T cells were separated with a subpopulation of T cells with low affinity for sheep erythrocytes. Decrease of this subpopulation was dependent on the decrease in Fcgamma+ T cells. Non-T cells with Fcgamma receptors were also diminished in SLE patients, but their decrease did not correlate with disease activity. The decrease in suppressor-cell function in SLE may be a result of loss, rather than of dysfunction, of the suppressor Fcgamma+ T cells.


Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema. Physiological comparison of adult normal and heterozygous protease inhibitor phenotype subjects from a random population. For plethysmographic studies of lung mechanics and measurement of pulmonary diffusing capacity, 62 subjects were drawn from a randomly selected population sample. Data obtained from the 24 subjects of heterozygous phenotype for alpha-1-antitrypsin deficiency (PiMZ) were compared by age group with data from 38 normal (PiM) subjects matched for sex, age, and smoking history. Comparison of mean values by age group for lung volumes, diffusing capacity, lung elastic recoil, maximum expiratory flow, and the occurrence of frequency dependence of dynamic compliance revealed no differences between phenotype groups. There was no evidence of an accelerated effect of aging among PiMZ subjects when compared with normal counterparts nor was there evidence of an increased effect of smoking. From these data it appears that the PiMZ phenotype per se is not a risk factor in the development of emphysema.


Suppressor-cell antibody in systemic lupus erythematosus. Possible mechanism for suppressor-cell dysfunction. Circulating antibodies that could be responsible for the suppressor thymus-derived (T)-cell dysfunction in active systemic lupus erythematosus (SLE) were investigated. Sera from 14 active and inactive SLE patients were compared with a pool of 22 normal sera. All sera were adsorbed with a pool of normal platelets to exclude antihistocompatibility leukocyte antigen antibodies; with AB erythrocytes to exclude isohemagglutinins; and with a pool of normal bone marrow-derived (B) lymphocytes, monocytes, and neutrophils to deplete anti-B-cell antibodies, Fc-receptor antibodies, and antibodies directed against neutrophils or monocytes. Sera from active SLE patients were capable of inhibiting the activation of normal, blood lymphocytes by concanavalin A to become suppressor cells. The latter were assayed by coculturing the concanavalin A-activated cells with autologous lymphocytes, which were then activated with either phytohemagglutinin for proliferative response or with pokeweed mitogen for B-cell immunoglobulin (Ig) synthesis and secretion. Specific incorporation of cultures with phytohemagglutinin showed a value of 67+/-13 (mean+/-SD) for suppressor cells treated with adsorbed, active SLE sera. This value was significantly different (P < 0.001) from that of cells treated with the inactive SLE sera or with the pool of normal sera. Similar findings were seen with respect to the B-cell target parameters. Cytoplasmic Ig and IgG in supernates of cultures with pokeweed mitogen showed values of 17+/-5% and 717+/-134 ng/culture, respectively, for suppressor cells treated with the adsorbed, active SLE sera. This was significantly different from those treated with the inactive SLE sera or with the pool of normal sera. The antisuppressor-cell factor was shown to be IgG, complement independent, not cytotoxic, active at 37 degrees C and at room temperature, but not at 4 degrees C, and adsorbable with T cells. Suppressor T-cell antibody in sera of active SLE patients could be responsible for the observed suppressor T-cell dysfunction seen in active SLE. The mechanisms responsible for the induction of the antisuppressor-cell antibody are unknown.


Some telencephalic connections in the frog, Rana pipiens. Some afferent, efferent and intrinsic connections of the telencephalon of Rana pipiens were studied using a horseradish peroxidase method. Afferents to the telencephalon from thalamic and brain stem cell groups were demonstrated. These findings, taken together with the results of previous studies, indicate that separate thalamic cell groups project visual, auditory and somatosensory information onto the striatum. A separate thalamic cell group projects to the medial telencephalic wall and probably conveys visual and somatosensory information. These telencephalic afferent systems do not appear to be directly comparable to those of birds and reptiles. Additionally, some telencephalic afferents demonstrated in previous studies using anterograde degeneration techniques were confirmed, and some intratelencephalic connections were identified.


Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. II. Details of dendritic development. The development of Purkinje cell dendrites was studied in the bullfrog from premetamorphic tadpoles to 10-week-old postmetamorphic frog-lets by the Golgi-Kopsch method. In this species two distinct patterns of arbor formation may be seen, which appear to be related to differences in the timing of initial dendritic development. In Purkinje cells that begin development in early tadpole stages, the dendritic tree is elaborated by continuous and concomitant growth and branching, a process by which the developing arbor expands in both height and width. Arbor formation in Purkinje cells that begin development in metamorphosing tadpoles proceeds in two separate steps. Initially, dendrites of such cells elongate, but form only a few poorly developed branches; only when the arbor reaches near-adult height does branching become extensive. Additional differences present in Purkinje cells are reflected in the paucity of growth cones and filopodia in the tadpole, and numerous filopodia and growth cones in the metamorphic period. An interesting feature of dendritic development in this species is a tendency to alter the arboreal domain by the formation of extra-arboreal dendrites, and possibly by the occasional resorbtion of other partially formed dendrites. The pattern of dendritic development in the frog is different than in mammals and is difficult to interpret. Such unusual development may be due to disturbances in the timing of the formation of Purkinje cell dendrites and of the establishment of the external granular layer (EGL).


Rapid high dose (RHD) contrast cranial computed tomography: a concise review of normal anatomy. This study illustrates detailed cerebral anatomy that can be consistently visualized on computed  tomography scans after a rapid high dose of contrast substance has been infused. A thorough knowledge of anatomy is required not only to detect and precisely localize lesions but to avoid ascribing pathological significance to normal, contrast  enhanced structures.