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E Lewis

Publications and source records attributed to E Lewis.

At least 19 recordsLinked to original sources

The expression of small heat shock proteins in the microfilaria of Brugia pahangi and their possible role in development.

Development of the microfilariae of Brugia pahangi in the mammalian host is blocked until uptake by a mosquito vector when the developmental cycle is re-initiated. Comparison of the profile of polypeptides labelled in microfilariae cultured at mammalian temperature (37 degrees C) or mosquito temperature (28 degrees C) revealed a complex of low-molecular-weight proteins (18 kDa and 22-24 kDa) synthesized only in microfilariae at 37 degrees C. The synthesis of these proteins was also induced by transfer of microfilariae to 41 degrees C (i.e., heat shock conditions), suggesting that these are heat shock proteins. The expression of the small heat shock proteins in the Brugia life cycle is developmentally regulated, as they are not observed in the mature adult female. Their synthesis is strictly temperature dependent and is repressed upon transfer of the microfilariae to 28 degrees C.

Aedes

Incorporation of circulating fibronectin into various tissues during sepsis: colocalization with endogenous tissue fibronectin.

We studied the plasma clearance and tissue incorporation of intravenously infused purified human plasma fibronectin into various tissues during a period of acute lung vascular injury induced by lethal postoperative bacteremia in sheep. Lung, liver, spleen, and heart tissue were examined for both endogenous sheep tissue fibronectin as well as the experimentally infused human fibronectin using dual-label immunofluorescence. Awake sheep (n = 4) received a postoperative iv infusion of 5 x 10(9) live Pseudomonas over a 60-min infusion interval. Bacterial challenge was started 2 hr after starting the iv fibronectin infusion of purified human plasma fibronectin (100 mg iv bolus; 4 hr iv at 100 mg/hr). Human fibronectin displayed a biphasic rate of clearance from the plasma with entrance into lymph. Human fibronectin readily incorporated in all tissues studied, including the lung which was the focus of vascular injury. Analysis of tissue sections by dual-label immunofluorescence indicated that the exogenous human fibronectin colocalized with the endogenous sheep fibronectin. Thus, the plasma fibronectin concentration may influence the lung vascular barrier due to its incorporation into the tissue pool of fibronectin. Moreover, the plasma may serve as a reservoir for soluble fibronectin which can enter and colocalize with the insoluble tissue pool of fibronectin in various tissues.

Animals

Kinetics of plasma fibronectin: increased lung tissue incorporation after postoperative bacteremia.

Fibronectin is an adhesive glycoprotein that may influence the permeability of the vascular barrier. We compared the plasma disappearance of purified human fibronectin (hFn) and its incorporation into lung tissue in control nonbacteremic and bacteremic sheep after surgery to determine the influence of postoperative bacteremia on the plasma clearance and lung deposition of hFn. Lymph fistulas were surgically prepared 48 h before either saline or bacterial challenge to allow for collection of timed samples of plasma, lung lymph, and peripheral lymph. On the day of the study, the sheep were anesthetized and given either 5 X 10(8) Pseudomonas aeruginosa in saline or saline alone. In parallel, they were infused intravenously with 100 mg of hFn, and the hFn concentration in plasma, lymph, and tissue extracts was subsequently determined by enzyme-linked immunosorbent assay over an 8-h experimental interval. Localization of endogenous sheep fibronectin (sFn) and the injected hFn in serial lung tissue samples was determined by dual-label immunofluorescence. In nonbacteremic control sheep, plasma hFn levels declined with an initial rapid slope (t1/2 = 0.53 +/- 0.19 min), followed by a second, gradual slope (t1/2 = 21.7 +/- 2.5 h), whereas the concentration of hFn in lung lymph and peripheral lymph rose exponentially with time. In bacteremic sheep, the early plasma disappearance of hFn was similar, but the second phase of plasma clearance was faster (t1/2 = 7.4 +/- 0.3 h). Lung tissue from control and bacteremic sheep contained the same level of extractable hFn. However, tissue extraction followed by immunofluorescence microscopy indicated that lung tissue from bacteremic sheep contained more nonextractable hFn than lung tissue from nonbacteremic sheep. Thus postoperative bacteremia that elicits acute lung vascular injury will increase the plasma disappearance of hFn and its incorporation into the lung tissue.

Animals

Human herpes virus infections and Alzheimer's disease.

Herpes viruses cause acute and chronic diseases of the peripheral and central nervous systems and have been implicated in the aetiology of Alzheimer's disease (AD). In this investigation the relevance of human herpes virus infection to AD was assessed by in situ hybridization. The abundant latency associated transcript(s) of herpes simplex virus type 1 (HSV-1) were detected at a significantly higher incidence in the trigeminal ganglia of individuals with AD than in controls. But we could find no evidence of viral RNA in the central nervous system (CNS), looking specifically in the hippocampal cortex of demented individuals with extensive neuropathological changes of AD. These studies solve one problem in testing the viral hypothesis of causation, i.e. the sensitivity of the methods used in the search for latent infection. But the central issue remains unresolved because of necessity, only the end stage of a prolonged pathophysiological process has been examined. Our conclusions are qualified accordingly.

Alzheimer Disease

Intradermal inoculation with Heptavax-B. Immune response and histologic evaluation of injection sites.

The high cost of hepatitis B vaccine has limited its widespread use. Low-dose, intradermal injections of vaccine represent one option for reducing the cost. In this study, 92 nonimmune medical students were given three 0.1-mL intradermal injections of Heptavax-B containing 2 micrograms of hepatitis B surface antigen (HBsAg) at 0, 1, and 6 months. By 6 months, 90% of the subjects had developed protective levels of antibody to HBsAg (greater than or equal to 10 mIU/mL). Follow-up at 1 year showed a geometric mean concentration of antibodies to HBsAg of 396 mIU/mL for the group, and 95% had levels of antibody to HBsAg greater than or equal to 10 mIU/mL. A level of antibody to HBsAg of greater than 100 mIU/mL also was observed in more than 75% of subjects. Side effects included induration of the inoculation site in 18% at 6 months, which disappeared by 12 months, and macules that persisted at 1 year in 63%. The administration of hepatitis B vaccine intradermally is an attractive, low-cost alternative in the United States, where universal vaccination of preschool children or adolescents is being contemplated, and where booster doses are being considered.

Adult

Perinatal death.

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Adult

Contribution of hepatic fibronectin synthesis to regulation of plasma fibronectin.

Intravenous injection of gelatinized particles, which are phagocytized by the reticuloendothelial system, elicits an acute depletion of plasma fibronectin followed by restoration to normal concentrations in 6-8 h and a rebound elevation at 24 h. We determined the contribution of hepatic fibronectin synthesis to the restoration of plasma fibronectin in rats after particle infusion by measuring the net incorporation of 75selenomethionine into plasma fibronectin during the recovery period. Rats injected intravenously with gelatinized particles had a greater (P less than 0.01) incorporation of labeled 75selenomethionine into fibronectin but less (P less than 0.05) incorporation of 75selenomethionine into total plasma protein than control rats. Inhibition (86%) of hepatic fibronectin synthesis by pretreatment with cycloheximide limited the recovery of fibronectin levels by only 60%, suggesting a source(s) other than hepatic synthesis may contribute to the restoration of plasma fibronectin. Using purified human plasma fibronectin as a tracer in the plasma pool, we found that 26% of the soluble fibronectin consumed from the plasma during particle clearance was subsequently released back into the plasma over a 4-h interval. Tissue analysis indicated that 125I-labeled fibronectin, which was previously incorporated into the tissues, was not released from the tissue pool after the injection of gelatinized particles. Thus the normalization and regulation of plasma fibronectin levels after its acute depletion due to blood-borne particles is a result of 1) an increase in hepatic synthesis of fibronectin, 2) the release of fibronectin previously consumed as an opsonin during particle clearance, and 3) the release of soluble intact fibronectin from a preformed storage pool.

Animals

Fibronectin fragments in lung lymph after thrombin-induced lung vascular injury.

Fibronectin is an adhesive glycoprotein found in plasma and lymph as well as between lung endothelial cells and their collagenous basement membranes. Fibronectin is highly sensitive to proteolytic cleavage. We determined if fragments of fibronectin appear in lung lymph in association with increased lung protein clearance after thrombin-induced intravascular coagulation. Thrombin was infused intravenously, (80 units/kg for 30 minutes) into sheep (n = 8) surgically prepared with chronic lung lymph fistulas. Plasma and lymph fibronectin was assayed by electroimmunoassay. Fibronectin fragments were detected using Western blot analysis. After thrombin infusion, lymph flow increased 650% above baseline within 1-2 hours in association with a 35% decline in lymph-to-plasma total protein concentration ratio. This was followed by a second phase (3.5-6 hours) of normalized lymph-to-plasma ratios coupled with sustained elevation of lymph flow. Lung protein clearance remained elevated (p less than 0.10) for 5.5 hours. Plasma fibronectin levels declined slightly over 1-5 hours (zero time = 597 +/- 64 micrograms/ml; 1.5 hours = 478 +/- 59 micrograms/ml) and then increased significantly (p less than 0.05) over 24-48 hours (760 +/- 85 micrograms/ml). The amount of low molecular weight fibronectin fragments in lung lymph increased over the 1.5-6 hours post-thrombin and then declined over 12-48 hours. Thus after thrombin infusion, fragments of fibronectin were usually detected in increased amounts of lung lymph in association with an elevation of lung protein clearance.

Animals

Management of perinatal loss of a twin.

The death of a twin during pregnancy or around birth gives rise to a bewildering confusion of thoughts and feelings that can impede mourning and disturb the bereaved mother's care of a surviving twin. Every effort should be made to give the parents and siblings an experience of the dead baby. Photographs especially can reduce confusion and assist reality testing and thus facilitate the grieving process and improve the care of the surviving twin.

Bereavement

Viral oncolysates in patients with advanced ovarian cancer.

Viral oncolysates (VO) derived from two cultured ovarian carcinoma cell lines infected with influenza A/PR8/34 were administered intraperitoneally (IP) to 40 patients with advanced ovarian carcinoma, including 31 with late-onset ascites and 5 with pleural effusions. PR8 virus-specific antigens and ovarian tumor-associated antigens have been demonstrated on two oncolysates designated OVO1 and OVO2. Thirty-five patients received 9 mg of a 1:1 mixture of OVO1 and OVO2, 5 patients received one or the other. During the first month three IP schedules were evaluated, i.e., single, biweekly, and weekly, which were followed by monthly injections. Intrapleural (IP1) injections of a 3.0-mg 1:1 mixture of OV1 and OV2 were administered to 3 patients concurrently with initial IP injections and to 2 patients following later development of pleural effusions. In 7 patients ascites disappeared; in 5 of these the number of cytologically detected malignant cells was markedly reduced, in 1 pleural effusion disappeared, and in 3 tumor masses were reduced. Tumor masses shrank also in 2 patients without ascites. Tumor reduction conformed to standard response criteria in 2 of the 5 patients. Response duration in the 9 responding patients lasted from 3 to 19 months and survival durations 4 to 42 months. Disease symptoms in 7 patients improved noticeably. Two of the 9 responders later developed unilateral pleural effusions that responded for 7 and 15+ months to a single IP1 injection. Seventeen patients experienced one or more treatment side effects including fever, nausea or anorexia, malaise, abdominal pain, and arthralgia, but in only 2 patients, both on the weekly schedule, was toxicity severe enough to require treatment withdrawal. Humoral responses to viral and tumor cell-surface antigens were frequently observed in patients demonstrating clinical activity.

Adult

Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis.

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.

Animals