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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 577 records · Page 32Linked to original sources

The identification of allo- and auto-lymphocytotoxic antibodies in serum, in the presence of rabbit antithymocyte globulin.

An enzyme-linked immunosorbent assay (ELISA) for rabbit immunoglobulin (Ig) was developed in order to investigate serum levels achieved by therapeutic doses of rabbit antithymocyte globulin (ATG) and their relationship to in vitro serum lymphocytotoxic activity. Twenty renal allograft recipients treated for acute steroid resistant rejection with ATG were studied, where possible, before, during and following their treatment with ATG. During therapy, peak serum levels of rabbit Ig were in the range 20-101 micrograms/ml with one exception of 404 micrograms/ml. After treatment, levels gradually declined to zero within 12 weeks. All sera with lymphocytotoxic activity were absorbed with platelets and treated with dithiothreitol so that reactivity due to anti-HLA antibodies and autoantibodies produced by the patient could be differentiated from each other and from serum ATG. Nine patients had detectable serum ATG associated with in vitro lymphocytotoxic activity. In two cases the lymphocytotoxicity was attributed solely to ATG; two had only anti-HLA antibodies; in one patient the lymphocytotoxicity was due to a combination of ATG and anti-HLA antibodies; two had autoantibodies; and for two, cytotoxicity was initially due to ATG and subsequently to the development of autoantibodies. The serum levels of ATG achieved during treatment could thus be quantified, and the important distinction between anti-HLA antibodies, autoantibodies and ATG clearly made.

Animals↗

Cytotoxic T lymphocytes. Their relevance in herpesvirus infections.

We have used recombinant vaccinia viruses expressing the cloned genes coding for glycoprotein B (gB) or glycoprotein D (gD) of HSV-1 to analyze the role of HSV-1--specific cytotoxic T lymphocytes (CTL) in antiviral immunity. Various studies in mice revealed that either vector could stimulate some aspects of HSV-1--specific immunity, but surprisingly, HSV-specific CTL were not induced. Even though gD appeared to be a target antigen for class II-MHC-restricted CTL, neither the gB or the gD vector was capable of forming a target-cell complex that was recognized by class I-MHC-restricted HSV-specific CTL. The inability of these major extracellular glycoproteins to act as CTL-target antigens was even more unusual in light of the ability of CTL to apparently recognize the immediate early genes of HSV, none of which are considered to be expressed on the surface of infected cells. The selective failure of either the gB or gD vector to induce numerous aspect of anti-HSV immunity in the absence of a CTL response allowed us to assess the consequence of this failure in terms of the level of protective immunity against HSV challenge seen in vector-immunized mice. These studies suggest that this failure to induce HSV-specific CTL appears to minimize the protective response to only efficiently protecting against low-challenge doses of HSV-1. These findings are discussed with relevance to the role of CTL in the control of herpesvirus infections.

Animals↗

Herpes simplex virus type 1-specific cytotoxic T lymphocytes recognize virus nonstructural proteins.

The specificity of herpes simplex virus type 1-specific cytotoxic T cells was examined with target cells expressing either input viral structural antigens or antigens resulting from permissive infection or cells from an interrupted infection in which they expressed predominantly nonstructural immediate-early proteins. These studies indicated that only an insignificant minority of cytotoxic T cells recognized the input viral antigens, whereas a significant proportion (20 to 35%) recognized target cells that expressed the immediate-early proteins despite the absence of serologically detectable viral antigens upon the infected cell surface. The finding that a significant proportion of cytotoxic T-cell populations obtained from the draining lymph nodes of mice acutely infected with herpes simplex virus type 1 also recognized immediately-early gene-expressing target cells indicates the importance of nonstructural herpes simplex virus proteins to antiviral immunity in vivo.

Cytotoxicity, Immunologic↗

Can psychological assessment address borderline phenomena?

Literature about psychological test findings in borderline disorders reflects changes in the meaning of the term and can be confusing when viewed from today's prespective. Most descriptions have referred to a concept of borderline schizophrenia. This paper reviews psychological assessment of borderline patients by means of the Rorschach, by using WAIS/Rorschach patterns, and, post-DSM-III, by using the MMPI. It focuses on the Rorschach's sensitivity to several dimensions relevant to borderline pathology. The concept that borderline disorders can include mild forms of affective and schizophrenic illness was examined by applying a Rorschach content scoring system to a borderline sample. The findings demonstrate Rorschach ability to identify borderline subtypes and offer independent validation of affective and schizotypal subtypes in the borderline realm.

Borderline Personality Disorder↗

Self-esteem of adolescent girls as related to weight.

The Rosenberg Self-esteem Scale was administered to 550 14- and 16-yr.-old (+/- 6 mo.) girls. Self-esteem scores were categorized by weight and weight by height. Scores on the Quetelet Index for obesity were correlated with self-esteem scores. Mean self-esteem of the low- and middle-weight by height group was significantly higher than the mean of the high-weight by height group. In analyzing weight alone, the self-esteem of the middle-weight group was significantly higher than the self-esteem of the high-weight group. The correlation of the obesity index and self-esteem indicated that as weight increased self-esteem decreased.

Adolescent↗

IL-1 and IFN-gamma increase vascular permeability.

We examined the effect of cytokines on vascular permeability in vivo. Wistar rats received intradermal injections of various cytokine preparations and the permeability index (delta PI) was calculated from the difference between the absorption values of cytokine- and vehicle-treated skin sections after the extraction of accumulated Evans blue vital dye. Injections of a mixture of recombinant interleukin-1 alpha and beta (Il-1 alpha, IL-1 beta) and interferon-gamma (IFN-gamma) caused a maximal increase of permeability after 30 min (delta PI = 2). The administration of single recombinant cytokines revealed that the increase of permeability is mainly due to the action of IL-1 beta (delta PI = 1.4) and IFN-gamma (delta PI = 2.9) (P less than 0.001) at doses of 1-20 microU per injection site. IL-1 alpha slightly increased vascular permeability, whereas recombinant IL-2 and recombinant tumour necrosis factor alpha had no significant effects. Histological observations revealed significantly increased numbers of degranulated mast cells in skin sections pretreated with IL-1 beta (P less than 0.005) or IFN-gamma (P less than 0.001). The cytokine-mediated rise of vascular permeability could be suppressed by pretreatment of the animals with the vasoactive amine antagonizing drugs methysergide, pizotifen and cyproheptadine. Our experiments indicate an important role of IL-1 beta and IFN-gamma as vasoactive substances besides their function as hormone-like messengers between leucocytes.

Animals↗

Influence of acetylsalicylic acid and BM 13177 on blood pressure and efficacy of antihypertensive drugs in spontaneously hypertensive rats.

The effects of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and of the TXA2 receptor antagonist BM 13177 on blood pressure and on the efficiency of antihypertensive drugs were investigated in spontaneously hypertensive rats (SHR). ASA and BM 13177 applicated once caused a significant, but short-lasting decrease in blood pressure in SHR. In contrast, repeated application of ASA (3 x 100 mg/kg) caused a slight, but significant increase in blood pressure. Pretreatment with BM 13177 (60 mg/kg i.v.) did not influence the antihypertensive effect of the drugs clonidine, propranolol and dihydralazine. Pretreatment of SHR with ASA intensified significantly the effect of these drugs on blood pressure, independent of their mode of action, and on heart rate (dihydralazine). The formation of TXB2 in the aorta thoracica in ASA pretreated SHR 20 min after drug application, was more strongly inhibited than was the formation of PGI2. Therefore the TXA2/PGI2 balance shifted in favor of the latter. However, in normotensive rats, ASA was without any effect on blood pressure and on the antihypertensive efficacy of the drugs. In conclusion it could be suggested that prostanoids are involved in the short term as well as in the long term regulation of the blood pressure and in the blood pressure lowering activity of drugs at least in a hypertensive state.

Animals↗

The mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: clearance of local infection.

We have shown that immunization of mice with a vaccinia virus recombinant expressing glycoprotein D of Herpes simplex virus (HSV)-1 will induce a variety of L3T4+ T cell responses. These included a HSV-specific delayed-type hypersensitivity response, T cell help for the induction of antiviral antibodies, and the ability to eliminate a challenge dose of HSV from the pinna. This protection against a subcutaneous virus challenge was not mediated by the delayed-type hypersensitivity response because intravenous inoculation of the vaccinia virus recombinant expressing HSV-1-gD induced a state of split tolerance. Thus, mice could still clear a HSV challenge inoculum from the pinna yet were unable to mount a HSV-specific delayed-type hypersensitivity response. Evidence is presented that suggests the protective response was, at least, in part mediated by a T cell-dependent induction of virus-neutralizing antibodies. Evidence is also presented that may suggest the failure of a vaccinia virus recombinant expressing HSV-1-gD to induce HSV-specific cytotoxic T cell responses appears to minimize the protective response to only efficiently clearing low 10(4) 50% tissue culture infective dose) challenge populations of virus. These findings are discussed with relevance to the immune control of HSV infections and to the future development of anti-HSV vaccines.

Animals↗

Characterisation of the structure and expression of the gene encoding a major female specific polypeptide of Schistosoma mansoni.

A previously described cDNA clone, pSF10, of Schistosoma mansoni encoding the very dominant female specific polypeptide (FSP) has been used to characterize the gene and its expression. The gene is detectable in different isolates of S. mansoni and is estimated to be present in 3 copies per haploid genome. The gene is not sex linked and exhibits neither amplification nor rearrangement concomitant with expression. Expression of the gene by parasites maturing in hamsters is first detected after 5 weeks when the RNA is present at 1/10 the level of that of 6 week worms. Although the FSP gene is specifically and highly expressed by egg laying female worms a corresponding polypeptide produced by the cell-free translation of RNA is not detectable. It was confirmed, however, that pSF10 does indeed encode a mRNA by DNA sequence analysis. The sequence demonstrated a mRNA containing a poly(A) tail and two open reading frames. One reading contains no methionine but is very high (47%) in glycine. This amino acid composition could account for the inability to detect the gene product by cell-free translation in the presence of [35S]methionine.

Animals↗

Posttransplant antidonor lymphocytotoxic antibody production in relation to graft outcome.

Serial serum samples from 266 recipients of primary renal allografts were monitored posttransplant for the presence of panel reactive lymphocytotoxic antibodies (PRA). The minimum posttransplant follow-up period was 18 months. Patients were classified according to whether or not they produced PRA before and/or after transplantation. The groups were as follows: PRA negative before and after transplant, -/-, 171; PRA positive before and negative after transplant, +/-, 5; PRA positive before and positive after transplant, +/+, 27; PRA negative before and positive after transplant, -/+, 63. Actuarial graft survival at 1 year for each group was 81.3%, 100%, 70.4%, 47.6%, respectively. Fifty-five of the 63 -/+ recipients were retrospectively crossmatched with posttransplant sera against stored donor lymphocytes. Of these, 50 (91%) were posttransplant cross match positive, and 37 (67%) have lost their grafts. In 23 of the 26 cases where an anti-HLA specificity was defined, the antibody was directed against antigens present in the donor but not in the recipient. These results clearly indicate that the production of PRA in recipients of renal transplants is associated with antidonor reactivity and poor graft outcome. The fact that these PRA were often directed against donor HLA antigens emphasizes one of the hazards of mismatching for HLA at transplantation.

Blood Transfusion↗

Suppression of delayed type hypersensitivity to herpes simplex virus type 1 following immunization with anti-idiotypic antibody: an example of split tolerance.

Intraperitoneal (i.p.) immunization with herpes simplex virus type 1 (HSV-1) or an anti-idiotypic antibody (anti-id C) prepared against a monoclonal antibody specific for glycoprotein C of HSV-1, tolerizes mice for an HSV-1 delayed type hypersensitivity (DTH) response. This tolerization could be adoptively transferred to naive X-irradiated mice by splenic T cells, and was specific for HSV-1 DTH. Thus, DTH-tolerized mice responded to vaccinia virus or HSV-2 challenge, while remaining tolerized for HSV-1 DTH. In addition, these animals demonstrated a form of split tolerance such that HSV antibody, cytotoxic T cell and lymphoproliferative responses were detected in vitro. Thus, anti-id C induced a T cell population capable of specifically suppressing the HSV-1 DTH response, mimicking the effect of i.p. and intravenous immunization with HSV-1 found previously.

Animals↗

Mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: cytotoxic T cells.

We used a transfected L cell and a vaccinia vector carrying the herpes simplex virus type 1 (HSV-1) gene coding for glycoprotein D (gD) to characterize HSV-specific T-cell responses. Various studies with mice revealed that the vectors could stimulate some HSV-specific T-cell responses. Although the majority of the T cells contributing to the HSV-1 gD-specific proliferative response were of the Lyt-2.1+ phenotype, cytotoxic T cells (Tc), surprisingly, were not induced by these gD vectors. Even though gD appeared to be a target for a class II major histocompatibility complex (MHC)-restricted killer cell, neither gD vector was capable of forming a target cell complex which could be recognized by class I MHC-restricted HSV-specific Tc. Further investigation of the gD-specific responses revealed the presence of potent suppressor cells and factors capable of inhibiting HSV-specific Tc induction in in vitro assays. One interpretation of these data is that class I MHC-restricted HSV- and gD-specific Tc do not develop during HSV infection because of active suppression.

Antigens, Viral↗

Cation dependence of posttetanic potentiation of neuromuscular transmission.

We have investigated the possibility that much of posttetanic potentiation (PTP) of quantal release of neurotransmitter at the frog neuromuscular junction may be due to posttetanic accumulation of [Ca2+]i, via a plasmalemmal Cao2+-Nai+ exchanger that is powered by an increase in Nai+ during the tetanus. Our new findings on the cationic dependence of PTP are consistent with this hypothesis. 1) Several manuevers that decrease Na+-K+ pump activity, (decreasing [K+]o, replacing K+o with Rb+o or Li+o, or adding acetylstrophanthidin to Ringers), all increase the intratetanic rise and prolong the posttetanic decay of epp quantal content (m) and miniature epp frequency (fmepp). 2) Increasing [Ca2+]i or [Sr2+]o, but not [Mg2+]o, increases posttetanic fmepp in a graded fashion. 3) PTP of fmepp is still present after addition of Mn2+o, which blocks voltage dependent Ca2+ entry.

Animals↗

A case of Charles Bonnet syndrome with musical hallucinations.

An 86-year-old woman with visual impairment who developed a vivid, visual hallucinatory state in clear sensorium is described. This picture conforms to the description of Charles Bonnet Syndrome. She also experienced musical hallucinations. The role of sensory deprivation in the pathogenesis of this syndrome is discussed.

Aged↗