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We reported a case of Buerger's disease presenting as acute sigmoid ischemia with perforation in a young male smoker. One year later, peripheral vascular disease was observed.

Peripheral lymphocyte subsets were enumerated, using OKT monoclonal sera, in 56 diabetic (43 adults and 13 children) and 20 control subjects. Concomitantly, anti-islet humoral and cellular immunity was tested in vitro and serum thymulin level was measured. In the newly diagnosed patients ( (1) the magnitude of T-cell depletion and/or imbalance in diabetic subjects depended mainly on the duration of the disease, (2) anti-islet cellular immunity was the anomaly most frequently detectable, and (3) a decrease in serum thymulin level was infrequently detected.

Anti-islet cell and anti-insulin antibody production was studies over a 12-mo period in 82 recently diagnosed diabetics randomly receiving either cyclosporin or placebo. Cyclosporin had only minimal effects on the production of anti-islet cell antibodies whether directed to islet cytoplasmic (immunofluorescence) or membrane (cytotoxicity assay) antigens even in patients undergoing remission. These data suggest that these antibodies do not play a major role in the pathogenesis of the disease particularly since their (irregular) presence is not predictive of the clinical response to cyclosporin. Conversely, cyclosporin completely suppressed the synthesis of antibodies elicited by exogenous insulin irrespective of the insulin doses received, and decreased the autoantibody production against thyroid antigens, indicating that cyclosporin has variable effects on antibody production against various antigens.

High spin states in /sup 75/Br were investigated in the reactions /sup 62/Ni(/sup 16/O,p2n) and /sup 66/Zn(/sup 12/C,p2n). By means of ..gamma gamma..- and ..gamma..-neutron multiplicity coincidence measurements, rotational bands of both parities were extended up to 7 MeV excitation energy and spin I = (33/2). The lifetimes of 17 yrast states were determined with the recoil distance and Doppler shift attenuation methods; the spin dependence of the side feeding time was also measured. The data have been analyzed in terms of the Strutinsky-Bogolyubov cranking model with a Woods-Saxon average potential. The first crossing observed in the negative parity bands is attributed to the alignment of a g/sub 9/2/ proton pair; the next irregularity which is also observed in the positive parity band is interpreted as the alignment of g/sub 9/2/ neutrons. The coexistence of prolate and oblate configurations at low spin and the change of nonaxial deformation with rotational frequency due to the polarization of the even-even core by the odd particle are discussed. The signature inversion visible in the negative parity bands as well as the changes in the signature splitting and reduction of B(E2) values at high spins may be related to a transition from ..gamma.. 0/sup 0/ triaxial shapes.« less

The alkaloidal content of of the stem barks of Hernandia cordigera has been studied and compared to that of other Hernandia species. Main alkaloids are phenolic aporphines.

Anti-islet immune reactions were studied in vitro in genetically diabetic homozygote C57BL/KsJ db/db mice, using murine islet cells as a target. Spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T-cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Anti-islet complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were also found in the sera of these mice. This anti-islet immunity was detectable as early as the tenth day of life and lasted throughout the entire life span of the animals. A significant lymphopenia was detected in thymus and spleen cell populations. None of these anomalies was found in control heterozygote mice. Thymic function was explored in the same mice by evaluating their serum thymic factor (FTS) levels using a rosette assay. The age-dependent decline of FTS levels was significantly accelerated in diabetic mice as compared with heterozygous littermates. Futhermore, FTS inhibitory immunoglobulins were detected in db/db mouse sera, which inactivated in vitro the biologic potency of synthetic FTS. Histologically, the thymus displayed an accelerated involution. It was shown by indirect immunofluorescence using anti-FTS monoclonal antibodies that the number of FTS+ cells was reduced in db/db mouse thymuses. Histologie study of the islets of Langerhans showed early signs of β-cell hyperactivity and hypertrophy, followed by β-cell rarefaction and profound dislocation of islet architecture. Insulitis was not detected.

The recent announcement of electrochemically induced nuclear fusion [1,2] has generated great interest and activity within the scientific community. In particular, there are several aspects related to the work of ref. 1 which are not fully understood and therefore deserve further investigation. One of them is the huge discrepancy between the amount of measured heat and the intensity of the supposedly accompanying nuclear radiation, namely neutrons and gamma rays. In view of the fact that the detection of nuclear radiation in the context of an electrochemical process is perhaps the most unequivocal fingerprint for the occurrence of fusion, we feel that a careful re-evaluation of the measurement conditions may be needed. In order to address this question, in the present paper we report on an attempt to observe this phenomenon and on the possible problems related to the detection techniques.

The BB rat develops a spontaneous type I diabetic syndrome with anti-islet autoimmunity. Sera from diabetic and nondiabetic BB rats (from diabetes-prone litters), nondiabetic BB rats (from low-risk lines), and nondiabetes-prone Sprague-Dawley rats were collected twice a week from age 40 days to 160 days. Sera were tested for: (1) complement-dependent toxicity to 51Crlabeled islet cells in vitro; (2) immunoglobulin binding to RIN-5 F insulinoma cells; and (3) ability to selectively suppress insulin secretion from normal islets in vitro. All sera from rats that subsequently became diabetic or glucose-intolerant were toxic to islet cells from various rat strains in the presence of complement. They were toxic neither to hepatocytes nor to fibroblasts. The toxic potency was associated with the globulin fraction. It was, in most cases, maximal either before or immediately after the onset of the disease. Sera from the nondiabetes-susceptible BB rats and the rats which, in diabetes-prone litters, died too early to be classified tended toward greater toxicity to islets. Immunoglobulins from diabetic sera bound to RIN-5 F cells more than did the serum globulins from other groups, their maximal binding capacity occurring afterthe onset of diabetes. Furthermore, BB diabetic sera were capable of selectively inhibiting the insulin secretion from normal rat islets in vitro either in the presence or, in some cases, in theabsence of complement. The A- and D-cell functions were not suppressed. The combination of such results suggests the presence of one or more antibodies capable of binding to beta cells, inhibiting their function, and inducing their lysis. These antibodies may contribute to the beta cell disruption in this model of diabetes.

To explore humoral immunity in insulin-dependent diabetic (IDDM) patients, we studied insulin release from isolated mouse islets stimulated by glucose + theophylline after incubation with the sera of these patients and complement. Eleven of 21 IDDM sera suppressed the stimulated insulin release while the arginine-stimulated glucagon release remained unchanged. Morphologic evidence and the trypan-blue exclusion test suggested that the suppression of insulin release was due to a cytotoxic effect of the sera. No beta-cell inhibition or morphologic damage was detectable in the presence of sera from 30 healthy subjects, 8 non-insulin-dependent diabetic patients, and 5 nondiabetic patients with autoimmune diseases. Beta-cell inhibition by IDDM sera was not observed when complement was omitted. After serum fractionation, the cytotoxic potency of IDDM sera was located in the immunoglobulin G fraction. Using human islets, insulin release was suppressed by 3 of 6 IDDM sera. Complement-dependent cytotoxicity was found in 1 of 5 recent-onset IDDM patients and 11 of 16 IDDM patients with autoimmune phenomena. It was associated in all cases with the presence of islet cell antibodies as detected by immunofluorescence, and with the presence of circulating lymphocytes which suppressed insulin release in vitro. Complement-fixing antibodies may contribute to the selective beta-cell damage in IDDM.

Lewis rats were used to study the development of humoral and cell-mediated cytotoxic reactions, as measured against fibroblast colonies of August rats, after (L×A)F1 skin allografts. Unmanipulated Lewis recipients were compared with Lewis recipients having received an enhancing Lewis anti-August serum along with the graft. The development of serum cytotoxicity was barely modified. Lymphoid cell cytotoxicity, on the contrary, was markedly delayed, but this was followed by a late rebound of this cell-mediated cytotoxicity, soon after the disappearance of any detectable serum cytotoxic antibodies.

Lymphocytes from insulin-dependent diabetic patients were previously shown to suppress insulin release from mouse islet cells in vitro. Glucagon release was not suppressed. In order to further analyze this phenomenon, lymphocytes from three insulin-dependent diabetic patients with associated autoimmune diseases were treated by using the panning method for cell separation before testing on islet cell suspensions. The OKT3+, OKT3-, and OKT4- cell subsets were obtained. Insulin release was suppressed by the OKT3+ (T lymphocyte-enriched) subset, but not by the OKT3- (T lymphocyte-depleted) subset. These results suggest that T lymphocytes are directly involved in the suppression of insulin release in this model. Furthermore, the OKT4- (T helper-depleted) subset also suppressed insulin release.

Anti-islet immunity was studied in six spontaneously insulin-dependent diabetic (IDD) dogs, using mouse islets of Langerhans cells as targets, in vitro. Insulinopenia was demonstrated in all dogs by an i.v. glucose tolerance test. A significant lymphocytopenia was detected in the peripheral blood of this diabetic group. Pancreatic tissue from one of these animals was obtained shortly after death and the islets displayed a marked loss in beta cells without significant changes in the other types of islet cells. No insulitis was observed. Circulating mononuclear cells from the diabetic dogs induced an increased basal insulin (IRI) release from islet cells and a suppressed stimulated IRI release. Damage to or depth of beta cells may account for these findings. The stimulated IRI release was also suppressed when islets were incubated with the diabetic sera + complement, while the D-cell response to arginine was not altered, and the A-cell response was reduced but not abolished. A lysis of islet cells in the presence of IDD sera + complement was demonstrated by an increased release of 51Cr from labeled cells. These anomalies were observed neither when complement was heat-inactivated nor in the presence of control sera + complement. Canine IDD may be a new animal model for the study of anti-islet cellular and humoral immunities.

The binding characteristics of chlorophenoxyisobutyric acid (CPIB) to serum proteins has been studied in 10 chronically uremic patients and 9 healthy subjects using the technique of equilibrium dialysis. Scatchard analysis of the results indicated a significant decrease in association constants for low as well as for high affinity sites. The number of binding sites however was not diminished thus suggesting the presence of competitive inhibitors. Such inhibitors were dializable, at least in part, as demonstrated by in vivo-hemodialysis and in vitro-dialysis experiments. The in vivo administration of 50 mg heparin intravenously led to a striking increase in the unbound fraction of serum CPIB whereas the addition of 10 IU/ml heparin in vitro induced no change of protein binding which is in favor of only an indirect effect of heparin. In conclusion, CPIB binding to serum proteins of chronically uremic patients as compared to normal volunteers was decreased leading to an increase of its unbound circulating fraction. The observed change of protein binding appeared to be due to the presence of competitive inhibitors in uremic serum.

This paper reviews the rosette inhibition test for the evaluation of antilymphocyte serum potency and reappraises the biological significance of the assay. Evidence is also presented which indicates the presence, in antilymphocyte serum, of immune complexes.

The diabetic db/db mice of the C57 BL/KsJ strain display anti-islet immunity, thymic dysfunction, and lymphopenia. In the present work, lymphocytes, T-cells, and T-cell subsets were enumerated in thymus and spleen from diabetic db/db mice and their db/ + heterozygote I irte r m ates from the 10th day to the 10th month of life. A significant lymphopenia was detected in thymus and spleen from the second month on, involving specifically the T-cell compartment, as assessed by use of a monoclonal anti-Thy1 antibody in indirect fluorescence. The study of T-cell subsets by monoclonal anti-Lyt1 and anti-Lyt2 antibodies revealed a significant increase in Lyt1+ cells and a decrease in Lyt2+ cells, with a corresponding increase of the Lyt1 + /Lyt2+ ratio. These anomalies appeared early in life, and were apparently linked neither with the degree of hyperglycemie nor with weight loss or infection. The T-cell depletion in thymus was more pronounced in young male (

We previously showed that circulating lymphocytes from more than 90% of insulin-dependent diabetics, block extra insulin secretion induced by stimulatory media in mouse pancreatic cells in vitro, without altering the secretion of glucagon. The present work demonstrates that this phenomenon depends on lymphocytes having the OKT3 marker, i.e., thymodependent lymphocytes. However, OKT4+ T helper cells are not required for the above phenomenon as proved by experiments using monoclonal sera against the OKT4 marker. When diabetes is associated with other autoimmune diseases, the pancreatic lymphocyte cytotoxicity observed in vitro is inhibited by the addition of a normal lymphocyte population; this could indicate that a "suppressor" factor is lacking in these patients. Conversely, addition of normal lymphocytes does not prevent lymphocyte cytotoxicity in diabetics without associated autoimmune diseases. Such a difference confirms the present trend to make a distinction between these two categories of diabetes.

Cyclosporin 5-10 mg/kg daily was given for 2-8 months to twelve recently diagnosed type 1 diabetics from a mean of 49 +/- SE 14 days after the start of insulin therapy, which was regulated to give near-normal blood glucose and haemoglobin A1c values. Mean insulin dosage dropped from 46 +/- 5 U/day before cyclosporin treatment to 16 +/- 4 U/day by the 7th month. Four patients had a complete remission and the insulin needs of four more were cut by half. The remaining four did not have remissions. Initial basal and glucagon-stimulated C peptide concentrations were higher in those who went into remission than in those who did not; they rose during cyclosporin treatment in the former but not in the latter. OKT4+ lymphocyte functions were suppressed in all patients and OKT4/OKT8 ratios declined. Anti-beta-cell autoimmunity, as indicated by lymphocyte-induced inhibition of insulin release from mouse islet cells, declined in all patients who went into remission. No consistent trend was observed for anti-islet cell antibodies. In forty-four similar, but non-randomised, recently diagnosed diabetics treated with insulin alone, the incidence of remission was 6%.

Antilymphocyte sera, either allogeneic or xenogeneic, may retain the antigen used for the immunization of the animal producing the serum in the form of antigen-antibody complexes, at least when the animal is bled within the first two weeks following the last immunizing injection. Evidence for this has been obtained in vivo and in vitro (3). Thus, antilymphocyte injections may contain not only antibodies but the antigens used to prepare the serum as well, and active immunization to these antigens can result in the human or animal recipient. In the heart-allografted rat, pre-transplantation injection of immune complexes prepared from alloantisera prolongs graft survival. The filtrate from these complexes, presumably containing antigens, also prolongs graft survival when administered in conjunction with nonspecific immunosuppresive drugs after transplantation. These results, however, do not allow determination of whether the effect is active or passive, or perhaps both, nor what is the action of the complexes themselves.

A significant inhibition of insulin response was found after incubation of islet cells with blood lymphocytes from 18 out 20 insulin-dependent diabetics. No inhibition was found in 22 control subjects.

The insulin response of isolated islet cells to glucose and theophylline in vitro was studied after incubation with lymphocytes. The test was employed to explore cell-mediated immunity in diabetics. A significant inhibition of insulin response to glucose and theophylline as compared to insulin release in a "basal" medium was found after incubation with blood lymphocytes from 21 out of 23 insulin-dependent diabetics (mean secretion index 18 +/- 18 versus 118 + 8 (SEM) % in control subjects). Most of the patients studied had associated autoimmune diseases: all of these displayed inhibition of insulin release. In six cases, the diabetes had a recent onset with no associated autoimmune disease: four of them displayed the same inhibition. No inhibition was found in the 26 control subjects and in seven non-insulin-dependent diabetics (mean secretion index 134 +/- 17 versus 145 +/- 23 (SEM) % in four control subjects). Lymphocytes inhibiting islet cell response were not cytotoxic against mouse fibroblasts. Twenty-two insulin-dependent diabetics showed islet cell antibodies to human and/or mouse pancreatic islets. However, an inhibition of insulin release was found with no detectable islet cell antibodies in one case, and the converse in two cases. Lymphocyte cytotoxicity to islet cells could play a role in the natural history of insulin-dependent diabetes.

In order to explore complement-dependent humoral immunity in insulin-dependent diabetic patients, their serum was incubated with Mouse isolated pancreatic islets in the presence of complement, after which the response of these islets to glucose was estimated by measuring insulin secretion. Out of 13 sera from insulin-dependent diabetic patients, 5 caused a significant inhibition of the insulin response. Morphological observation of islets suggested that this inhibition was due to a cytotoxic effect of the sera. In the absence of complement, the same sera were not able to suppress insulin release. No beta-cell inhibition or morphological damage was detectable on islets incubated with sera from 13 healthy subjects and 4 non-insulin dependent diabetic patients, in the presence or in the absence of complement. Complement-dependent humoral immunity may play a role in the beta-cell injury of insulin-dependent diabetes.

Mice peritoneal macrophages obtained after i.p. injection of a medium containing thioglycollate (Institut Pasteur, Paris) have increased levels of beta glucuronidase and acid phosphatase, when compared with macrophages obtained without previous thioglycollate injection. The maximum increase is observed between 7 and 10 days after injection and reaches up to 3 to 4 times the normal activity. When using separately the various components of the medium, the same phenomenon may be observed but never to the same degree. The injection of thioglycollate also produces: a) an increase in total number of peritoneal cells, and b) an increase in the percentage of macrophages among these cells. Kinetic studies suggest that thioglycollate injection first induces an increase in the number of peritoneal macrophages and subsequently macrophage modifications resulting in lysosomal enzyme increase.

Macrophage-rich adherent peritoneal cells from mice sensitized by two i.p. injections of allogeneic cells at days -- 12 and --2, were found non-specifically cytotoxic against (a) tumoral target cells, as evaluated by the chromium release test, and (b) normal target cells, as evaluated by a functional test based on the insulin secretion response to glucose stimulation of isolated pancreatic islet cells. This non-specific cytotoxicity was identical to that of macrophages "activated" by an in vitro incubation with supernatants of MLC between allograft donor and recipient as reported elsewhere. Moreover this cytotoxicity was not abolished by anti-theta serum treatment of adherent peritoneal cells before contact with target cells. It is concluded that an in vivo macrophage activation was obtained in our experiment. Using this same model, we found that the survival time of skin grafts from male C57BL/6 to female C57BL/6 mice was shortened if the graft was performed at the time when the recipient macrophages were found non-specifically cytotoxic (two days after the second allogeneic cell injection). The role of macrophage cytotoxicity in this accelerated allograft rejection is suggested by (a) the lack of any detectable cross-histocompatibility antigens between the immunizing cells and the skin graft, and (b) the absence of any alteration of the graft survival if the second immunizing injection two days prior to grafting is omitted (in that case only lymphocytes are found specifically cytotoxic against the strain of injected cells, while the non-specific cytotoxicity of macrophages is lacking).