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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 19 recordsLinked to original sources

Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection.

The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose-dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.

Animals

From front line to home front: a study of secondary traumatization.

While the long-term effects of combat trauma on veterans have been studied extensively, its impact on veterans' wives has yet to be investigated. This study examined the implications of combat-induced psychopathology--wartime combat stress reaction (CSR) and current posttraumatic stress disorder (PTSD)--in a sample of 205 wives of Israeli combat veterans of the 1982 Lebanon war. Results show that both CSR and PTSD were associated with increased psychiatric symptoms in the wives. In addition, current PTSD was particularly found to contribute to impaired social relations among veterans' wives in a broad range of contexts, from inner feelings of loneliness, through impaired marital and family relations, and extending to the wider social network. Implications of these findings for treatment and further research are discussed.

Analysis of Variance

Comparison of functional activity in host and graft mesenteric lymphoid tissue of rats receiving syngeneic heterotopic small bowel allografts with portal or systemic drainage.

With the accompanying paper these studies provide further evidence that functionally important lymphoid cell trafficking takes place in mesenteric tissue under the apparent control of factor(s) filtered by hepatic tissue. The role that these regulatory mechanisms have to play on survival of vascular allografts with venous drainage into either the portal or systemic circulation remains to be elucidated.

Animals

Altered cell trafficking in mesenteric lymphoid tissue following syngeneic heterotopic small bowel transplantation in rodents.

These data indicate that in rat heterotopic syngeneic SBT, the venous drainage system of the graft has profound effects on cell recovery in the gut-associated lymphoid tissue of both graft and host. Depending on the functional status of the same lymphoid tissue (Gorezynski, personal communication, 1992) one could thus anticipate significant perturbation of host-antigraft (and GVH) reactivity in allogeneic situations according to the venous drainage used. The mechanism(s) responsible for these effects have not been investigated. However, one testable hypothesis is that (a) factor(s) from the gut can control lymphoid recirculation within the mesenteric lymphoid tissue, and that this (these) factor(s) are absorbed under normal circumstances by hepatic tissue.

Animals

[Management of the scarred uterus].

On the basis of 899 cases of uterine scarring following cesarean section, the authors carried out a prophylactic cesarean in 42% of cases. Labor ended in childbirth by the genital tract in 44% of cases. The very low incidence of uterine rupture since segmental hysterotomy has become widespread and the improved fetal and maternal prognosis are all reasons to prefer delivery by the genital tract. One of the factors in choosing the method of childbirth is radiopelvimetry and estimation of the fetal weight; however, the suspicion of a threshold pelvis is not a contraindication to the labor test which was successful in 70% of the authors cases. On condition that strict obstetrical monitoring is possible, oxytocic drugs can be used to induce labor or correct hypokinesia and to administer a peridural analgesic. Routine extraction is no longer necessary during the expulsion phase but the authors remain faithful to uterine revision. In general, the labor test should be suggested as often as possible and should receive the same monitoring and treatment methods as for an intact uterus.

Birth Weight

[Monitoring after total hip prosthesis. Value of semi-quantitative D-dimer assay].

Criteria for positive assay of the D-dimer were defined in order to establish its diagnostic value for phlebitis in the post-operative period. A retrospective study was carried out on the files of 94 patients who had received a total hip prosthesis in 1990. A semi-quantitative assay technique was used to measure the D-dimer because it is the only method giving immediate results. Three criteria were used to classify the results: criterium A: D-dimer greater than or equal to 2 micrograms/ml; criterium B: D-dimer greater than or equal to 4 times the preceding test; absence of both of these criteria. The results were compared to echo-doppler results and confirmed by phlebography when necessary. The incidence of proximal phlebitis was low (2 percent); criterium B showed a 100 percent negative predictability and a 29 percent positive predictability. None of the cases of phlebitis diagnosed with this test had been suspected clinically. This test provides a means of patient screening and spares the need for other explorations.

Echocardiography, Doppler

Changing trends in preterm childbirth.

Progress in perinatal care has been accompanied recently by increasing numbers of induced premature deliveries because of fetal distress. This is confirmed by study of 26,796 consecutive births in the Caen Hospital Group between 1980 and 1987. Study of the fate of these children shows that this attitude has not led to any excess mortality when the share of the IPD before 32 weeks are regularly growing. This would imply that the prematurity rate is no longer a sufficiently accurate epidemiological index for the evaluation of prenatal care policies.

Female

Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro.

The cellular basis for the variation in induction of monocyte procoagulant activity (PCA) by murine hepatitis virus strain 3 (MHV-3) was examined using a set of recombinant inbred strains of mice derived from the resistant (A/J) and susceptible C57B1/6J (B) progenitors. Induction of PCA by MHV-3 required live virus and host protein and RNA synthesis. Absolute restriction for induction of PCA was observed at the level of the macrophage. Peritoneal macrophages from resistant parental A/J and RI strains (AXB5) could not be induced to express PCA when stimulated by MHV-3 alone or in the presence of lymphocytes from susceptible and H-2 compatible RI mice (AXB3) although they did respond to endotoxin (LPS). In contrast, macrophages from both susceptible (AXB3) and semisusceptible (AXB1) RI strains of mice expressed a similar increase in PCA after stimulation with MHV-3 in the absence of lymphocytes. The levels of PCA expressed by macrophages in the presence of Thy-1.2+ lymphocytes correlated with susceptibility to disease. Thy-1.2+ lymphocytes from susceptible RI AXB3 mice could induce levels of PCA in macrophages from semisusceptible RI AXB1 mice equivalent to that seen in cultures of macrophages and lymphocytes from susceptible mice. Further subfractionation of Thy-1.2+ cells demonstrated that L3T4+ cells instructed macrophages to produce PCA. Thy-1.2+ cells from MHV-3 immunized resistant AXB5 mice, but not from non-immunized mice, were able to suppress induction of PCA. This suppressor cell activity could be detected 4 days after immunization, reaching maximal activity at day 7 with significant suppression even at 28 days. The PCA was shown to have direct prothrombin cleaving activity (prothrombinase) by ELISA and immunofluorescence staining using the mAb 3D4.3. These results demonstrate that induction of a unique PCA (prothrombinase) is restricted at the level of the macrophage and define a regulatory role for T lymphocytes in its induction.

Animals

Pharmacodynamic aspects of spaceflight.

Little is known at present about the effects of human exposure to microgravity on the pharmacodynamics of medicinal agents. Considering the known physiologic perturbations associated with spaceflight and the effects of some of these perturbations on the pharmacodynamics of certain medicinals that act on the central nervous system, it is likely that the pharmacodynamics of at least some of these agents will be altered in individuals who are subjected to microgravity and other conditions of spaceflight. It is timely to initiate formal studies, initially in ground-based animal models and human volunteers during prolonged, head-down bed rest and eventually in animals and human volunteers exposed to microgravity, of pharmacodynamics and pharmacokinetics during spaceflight.

Animals

Kinetics of drug action in disease states. XXXVIII: Effect of body temperature on the convulsant activity of pentylenetetrazol in rats.

The purpose of this investigation was to determine the effect of body temperature on the pharmacodynamics (convulsant activity) of pentylenetetrazol (PTZ). Rats received an iv infusion of PTZ until the onset of maximal seizures, at which time samples of cerebrospinal fluid (CSF), brain, and blood (for serum) were obtained for subsequent determination of PTZ concentrations by HPLC. The PTZ infusion caused a decrease in body temperature of approximately 4 degrees C within 20 min and onset of seizures in approximately 40 min. Compared with animals whose temperature was maintained in the normal range by heating pads, the hypothermic rats required significantly larger doses and higher serum, brain, and CSF concentrations of PTZ to produce seizures. Other rats received an injection of brewer's yeast to produce fever. Then, PTZ was infused 6, 12, or 24 h later when body temperature was elevated by an average of 1.3, 1.1, or 0.4 degrees C, respectively. Compared with control rats, whose temperature was maintained in the normal range by heating pads, moderate hyperthermia had no significant effect on the dose and concentrations of PTZ required to produce maximum seizures. Pentylenetetrazol exemplifies a drug that can produce hypothermia which, in turn, reduces the sensitivity of rats to its pharmacologic action. Unlike the central nervous system (CNS) depressants phenobarbital and ethanol, whose pharmacologic activity in rats is enhanced at elevated body temperature, the activity of the CNS stimulant PTZ is apparently not altered by fever.

Animals