Crisis intervention and suicide prevention from a rural perspective.
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Crisis Intervention↗
Biomedical subjects
D A Clark
Publications and source records attributed to D A Clark.
Controversies in reproductive immunology.
Nine areas of current controversy in the field of immunology of reproduction have been selected for discussion: (1) do antisperm antibodies cause infertility; (2) does cell mediated immunity cause infertility; (3) do antibodies cause spontaneous abortion; (4) is abortion due to rejection of the "fetal allograft"; (5) is altered antigen expression crucial for survival of the "fetal allograft"; (6) is abortion mediated by graft rejection mechanisms; (7) does locoregional suppression prevent abortion; (8) does immunization to prevent abortion and promote pregnancy act via immunotropism and cytokine cross-talk; (9) do immune responses prevent spontaneous abortion in humans? The reasons for debate and uncertainty are reviewed and current data considered in an attempt to arrive at the most likely answer to each question. Directions for future research are proposed where appropriate.
Abortion, Spontaneous↗
Mesenteric vein thrombosis associated with a familial deficiency of free protein S.
Signs and symptoms of an acute intra-abdominal emergency developed in a 26-year-old man; this emergency prompted surgical exploration. It was discovered that he had a devitalized small bowel as a result of mesenteric vein thrombosis. An extensive evaluation for hypercoagulable states disclosed that he had a normal total protein S concentration, but by assay and on crossed immunoelectrophoresis studies, he had a decreased concentration of free protein S. A family study demonstrated protein S deficiency in his father and in a sister. On a subsequent determination, the propositus had a decreased concentration of total protein S. This case illustrates the association of protein S deficiency with mesenteric thrombosis and serves to caution that a single determination of total protein S is not an adequate evaluation when the index of suspicion for a hypercoagulable state is high.
Adult↗
Demonstration of a splenic cytotoxic effector cell in mice of genotype SCID/SCID.BG/BG.
Splenocytes from mice of genotype scid/scid.bg/bg were tested in vitro to characterize the nature of the immunological deficit in these doubly mutant animals. The cells were unresponsive to the mitogens LPS and Con A and to alloantigens, as predicted for scid/scid genotype. Splenocytes from scid/scid.bg/bg lysed the NK cell-sensitive target cell line YAC at levels approximately 50% lower than those observed for scid/scid splenocytes. Splenocytes from SCID-beige mice failed to lyse the NK-resistant, LAK-sensitive cell line P815 but showed high levels of activity against the murine placental cell line Be6. Lytic activity was found in both nonadherent and plastic adherent cells and was eliminated by pretreatment of the effectors with anti-asialo-GM1 and complement. Incubation of 1 x 10(5) splenocytes with hrIL-2 failed to induce blastogenesis in scid/scid.bg/bg cells but produced a response in cultures of scid/scid or bg/bg spleen cells. However, blastogenesis and elevated levels of LAK-type killing were observed following incubation of higher numbers of scid/scid.bg/bg splenocytes in hrIL-2. Thus, doubly mutant scid/scid.bg/bg mice have reduced NK cell activity, in comparison to scid/scid mice, and appear to possess LAK-like effector cells and LAK cell precursors.
Animals↗
The seroepidemiology of human herpesvirus-6 (HHV-6) from a case-control study of leukaemia and lymphoma.
Sera from an epidemiological case-control study of leukaemias and lymphomas conducted between 1980 and 1986 were examined for reactivity to human herpesvirus-6 (HHV-6) by an indirect immunofluorescence assay. Statistical analyses of the data revealed higher HHV-6 seroprevalence and antibody titres in the cases, particularly evident in the disease subtypes acute myeloid leukaemia, Hodgkin's disease (HD), and low-grade non-Hodgkin's lymphoma. Within the control group alone, HHV-6 seroprevalence was placed at 55% at a serum dilution of 1:40. The controls also displayed higher seropositivity in females as compared with males. Further analyses suggest an association of increased HHV-6 seropositivity and geometric mean titre ratio with HD among young adults lacking social contact in the family group. This finding might indicate late exposure to HHV-6 in such persons and could possibly signify late exposure to a number of viruses, including those hypothesized as playing a role in the aetiology of HD. Previous reports have nominated Epstein-Barr virus as a possible candidate. Our results suggest that HHV-6 should be included in further investigations of the aetiology of HD.
Antibodies, Viral↗
Murine pregnancy decidua produces a unique immunosuppressive molecule related to transforming growth factor beta-2.
Non-T small lymphocytic suppressor cells in murine allopregnancy release a potent immunosuppressive factor in vitro that is neutralized by rabbit anti-transforming growth factor (TGF)-beta. Previous studies have suggested that the decidual suppressor factor (DSF) is smaller than TGF-beta 1, and in this paper, we show that DSF on HPLC-sieving columns also elutes later than TGF-beta 2. Nevertheless, DSF has the ability to promote anchorage-independent growth of NRK fibroblasts similar to TGF-beta s. Using turkey antibodies specific for TGF-beta 1 or beta 2, we show that DSF is related to TGF-beta 2 rather than TGF-beta 1, and this relationship was confirmed by using a panel of murine mAb to TGF-subtypes. PAGE and Western blotting showed that the TGF-beta 2-reactive molecules in HPLC-purified DSF was slightly smaller than TGF-beta 2 and approximately 20 to 23 kDa. The DSF molecule is therefore closely related to TGF-beta 2 but as released from decidua, differs in size. The TGF-beta 2-related decidual suppressor factor was also obtained from the decidua of synpregnant C.B.-17 severe combined immune deficiency (SCID) and pregnant SCID-BG (C57BL/6 background) mice, confirming the lack of T or B cell dependence of DSF production and the generality of production of a TGF-beta-related suppressor factor by decidua associated with successful pregnancy in mice.
Animals↗
Detection of human herpesvirus-6 DNA in peripheral blood and saliva.
Saliva and peripheral blood samples from 20 healthy adults were examined for the presence of human herpesvirus-6 (HHV-6) DNA sequences using the polymerase chain reaction. Eighteen out of 20 whole saliva samples contained detectable HHV-6 genomes. The majority of peripheral blood samples were also positive; however, the results suggest that only a rare cell in the peripheral blood is infected. Serological studies did not reveal any correlation between HHV-6 antibody titre and the ability to detect HHV-6 DNA. The data indicate that HHV-6 genomes persist in the peripheral blood and oropharynx or salivary glands of most healthy individuals following primary infection.
Adult↗
Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis.
We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.
Acid-Base Imbalance↗
Decidua-associated suppressor activity and viability of individual implantation sites of allopregnant C3H mice.
Release of soluble suppressor activity from individual implant site decidua of DBA/2-mated C3H/HeJ mice was measured on days 12.5-13.5 of pregnancy. Suppressor activity varied among sites and followed a distribution curve that was displaced towards low suppression when resorption sites were compared to healthy embryonic implants. Pre-immunization against the DBA/2 strain paternal antigens failed to increase resorption (by loss of low suppression implants) but led instead to a reduced resorption rate. This was associated with an increase in soluble suppressor activity obtained from decidua. Some reduction in resorption occurred independent of an increase in the level of suppression suggesting additional contributing factors to the immunization effect.
Animals↗
A knowledge-based architecture for protein sequence analysis and structure prediction.
Methods for analyzing the amino-acid sequence of a protein for the purposes of predicting its three-dimensional structure were systematically analyzed using knowledge engineering techniques. The resulting entities (data) and relations (processing methods and constraints) have been represented within a generalized dependency network consisting of 29 nodes and over 100 links. It is argued that such a representation meets the requirements of knowledge-based systems in molecular biology. This network is used as the architecture for a prototype knowledge-based system that simulates logically the processes used in protein structure prediction. Although developed specifically for applications in protein structure prediction, the network architecture provides a strategy for tackling the general problem of orchestrating and integrating the diverse sources of knowledge that are characteristic of many areas of science.
Amino Acid Sequence↗
Are there immune abortions?
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Abortion, Spontaneous↗
Analysis of immunosuppressive molecules associated with murine in vitro fertilized embryos.
Supernatants from mouse in vitro fertilized (IVF) oocyte cultures may suppress in vitro lymphocyte proliferation stimulated by concanavalin A (Sigma, St. Louis, MO). Supernatants conditioned by incubation with mouse epididymal sperm alone were even more inhibitory. Thin-layer chromatography suggested the polyamines spermine in sperm and spermine plus spermidine in IVF embryo supernatants were responsible. Putrescine was not suppressive. In vitro fertilized oocytes from old CBA/J-strain mice (greater than 20 weeks) that suffer age onset infertility lacked suppression and manifest cleavage arrest that could be partially reversed by adding spermine to the cultures. The failure of IVF oocytes to produce adequate quantities of polyamines could lead to failure of implantation due to division arrest. A possible in vivo role of polyamines as immunosuppressor factors is discussed.
Animals↗
Intraluminal pathogenesis of necrotizing enterocolitis.
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Animals↗
Cognitive specificity and positive-negative affectivity: complementary or contradictory views on anxiety and depression?
A principal factor analysis, conducted on a mixed psychiatric outpatient sample (N = 470), identified both common and specific dimensions underlying anxiety and depression. Although an initial single-factor extraction accounted for a significant proportion of variance in cognitive and symptom measures of anxiety and depression, a two-factor solution, in which anxiety and depression formed separate dimensions, proved to be the better solution. MANOVAS performed on pure depressed, pure anxious, and mixed anxious/depressed subgroups provided evidence of a specific cognitive profile for anxiety and depression. The mixed subsample evidenced greater severity, a mixed cognitive and symptom profile, and character traits that may indicate increased vulnerability to psychological disturbance. Results are discussed in terms of Beck's (1976) cognitive content-specificity hypothesis and the positive-negative affect model (Watson & Tellegen, 1985).
Adaptation, Psychological↗
A morphological and immunological study of human placental bed biopsies in miscarriage.
Placental bed biopsies were examined in three groups of pregnant women for maternal vascular response to placentation as well as for the presence of cells associated with local immunosuppression activity. In the group of women undergoing legal abortion, the histological appearance of trophoblastic invasion was normal in all but one, and the proportion of immunosuppressor cells was also normal. In the missed miscarriage group the histological appearances were abnormal except in one patient. In women with a history of recurrent miscarriage who had miscarried after immunization, placentation was normal in some and defective in others. Immunosuppressor cells appeared to be diminished in number, although there was no correlation between the cytotoxic status of their sera and their pregnancy outcome.
Abortion, Habitual↗
Paraimmunology in the decidua?
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Abortion, Spontaneous↗
Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy.
In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)alpha, gamma-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortion-prone (CBA/J x DBA/2) and non-abortion prone (CBA/J x BALB/c,C3H x DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA x DBA/2, from 7 to 89% in CBA x BALB/c, from 5 to 47% in C3H x DBA/2. The effect was both gestational age- and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J x DBA/2 mating combination, whereas the rates in CBA/J x BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharide (LPS), which is known to lead to the release of TNF-alpha, had a similar effect, leading to gestational age- and dose-dependent enhancement of resorptions up to 100%. However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J x DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.
Animals↗
Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice.
The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM.
3-Hydroxybutyric Acid↗