A member remembers: charter member Evelyn Vrendenburg Ryerson recalls early days.
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Anniversaries and Special Events↗
Biomedical subjects
G Baldwin
Publications and source records attributed to G Baldwin.
Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock.
Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10 micrograms/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = .005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.
Animals↗
Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock.
BACKGROUND AND METHODS: Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with i.v. immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for i.v. use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with i.v. meningococcal endotoxin (lipo-oligosaccharide) 10 micrograms/kg, and treated with either a 2-hr i.v. immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone. RESULTS: Compared with untreated control animals, pulse rate increased (p less than .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p less than .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p greater than .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p less than .03) lower in the immunoglobulin-treated animals at 60, 120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p greater than .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) of ten immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs. CONCLUSIONS: In this model of circulatory shock in rabbits, i.v. immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.
Analysis of Variance↗
Effect of meningococcal endotoxin in a rabbit model of shock.
Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis. To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model. Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied. After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted. Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg. Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly. Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS. Survival was recorded. One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used. Pearson's coefficients were calculated. Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP. With progression of the shock state, the pH decreased and hypotension ensued. Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr. TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS. Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached. There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine.
Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex and multilineage hematopoietic defects were treated with recombinant granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) in a phase I/II trial. All patients were neutropenic and anemic after withdrawal of all bone marrow-suppressive drugs. Daily, G-CSF was subcutaneously self-administered until an absolute neutrophil count (ANC) greater than 6,000/microL was achieved and maintained for 2 weeks. Subcutaneous EPO was added to the regimen and the dose increased until an increase of 15 g/L of hemoglobin was observed. Groups of patients were administered increasing doses of zidovudine to determine their tolerance. G-CSF and EPO therapy was continued with dose modification to maintain an ANC greater than 1,500/microL and hemoglobin greater than 100 g/L. The dose of zidovudine was not altered. All 22 patients responded to G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2 weeks. Significant increases in CD4 and CD8 cell number, lymphocyte proliferative response, and bone marrow cellularity were seen. EPO therapy increased hemoglobin in all 20 evaluable patients within 8 weeks. Sixteen patients received 1,000 mg and four patients received 1,500 mg of zidovudine per day. The reinstitution of zidovudine resulted in a decline in reticulocytes and hemoglobin and the reappearance of transfusion requirements in eight of the 20 patients, six of whom had the study medications stopped. No patient had the study medications stopped because of neutropenia or thrombocytopenia. Toxicities were mild and did not require dose modifications. Limiting dilution plasma and lymphocyte co-cultures for HIV as well as serum p24 antigen levels did not change significantly during G-CSF or combined G-CSF and EPO therapy. HIV p24 antigen decreased significantly with zidovudine therapy. Opportunistic infections occurred in 14 patients but were successfully treated with myelosuppressive antimicrobial agents, including ganciclovir, without the development of neutropenia. These results suggest that combined therapy with G-CSF and EPO may improve the neutropenia and anemia of AIDS. Combined therapy may allow the resumption of full-dose zidovudine in most patients intolerant of the hematologic effects of zidovudine without apparent alteration of HIV expression or the efficacy of zidovudine.
Acquired Immunodeficiency Syndrome↗
Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins.
Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24-h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.
Animals↗
Monoclonal antibody to the gastrin receptor on parietal cells recognizes a 78-kDa protein.
Four monoclonal antibodies reactive by immunofluorescence and by flow microfluorimetry with canine and porcine gastric parietal cell membranes were produced by fusion of mouse NS-1 myeloma cells with splenocytes from mice immunized with a population of canine gastric mucosal cells containing 60-70% parietal cells. One of these, an IgM antibody designated 2C1, reacted with the surface membranes of parietal cells by immunofluorescence, flow microfluorimetry, and immunogold electron microscopy; competed with 125I-labeled gastrin for binding to gastric cells; and inhibited by 56% maximal gastrin stimulation of [14C]aminopyrine uptake in parietal cells. The antibody immunoprecipitated 125I-labeled samples of a 78-kDa gastrin-binding protein purified from membrane extracts of porcine gastrin mucosa but did not recognize the same protein labeled covalently with 125I-labeled gastrin-(2-17)-hexadecapeptide. These observations suggest that the previously identified 78-kDa gastrin-binding protein is the gastrin receptor and that the antibody 2C1 is directed against the gastrin binding site of the gastrin receptor.
Aminopyrine↗
Chloride transport stimulatory factor in human urine: effects on sodium fluxes and preliminary characterization.
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Adult↗
Preliminary crystallographic data for beta-lactamase I from Bacillus cereus 569.
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Bacillus cereus↗
Effective treatment of self-injurious behavior through a forced arm exercise.
A forced arm exercise was investigated as a means of eliminating head-hitting in two children. During sessions restraints used to manage subjects were removed. After a baseline measure, required practice of repeated vertical arm movements was made contingent upon each response. Later, this procedure was combined with reinforcement under a differential reinforcement of other behavior schedule. Arm exercise alone produced a substantial decrease in head-hitting, while the combination treatment engendered near-zero levels. Subsequently, reduction of head-hitting was extended to several contexts by regular ward staff. This type of treatment appears as effective with self-injurious behavior as it is with stereotyped behavior.
Arm↗
Chloride-transport stimulatory factor in urine of chronically sodium-chloride loaded man.
Urinary extracts (in methylene dichloride) of subjects on high sodium-chloride (NaCl) intake produce net Cl- efflux (active transport) in isolated short-circuited frog skin. Activity is not found in the urine of NaCl-deprived normal subjects or NaCl-loaded subjects with adrenal insufficiency. These findings suggest that presence of an adrenocortical steriod which participates in adaptation to high salt intake. We describe here a lipid-soluble factor extracted from urine of chronically salt-loaded subjects which stimulates active Cl- transport in isolated frog skin. Our findings indicate that the factor is of adrenal origin and that it induces active ion transport in the direction opposite to that stimulated by the adrenal hormone, aldosterone. Aldosterone produces NaCl conservation in states of salt deprivation. We expect this new factor to produce NaCl excretion in states of excess salt ingestion.
Adrenal Cortex Hormones↗
Ouabain, acetazolamide, and Cl-flux in isolated frog skin: evidence for two distinct active Cl-transport mechanisms.
Two distinctly different mechanisms for active Cl- transport in epithelia may exist: one, ouabain-sensitive and cation-dependent, and the other, acetazolamide-sensitive and cation-independent. As a test of this hypothesis the three active Cl- transport systems in isolated short-circuited skin of Rana pipiens were examined. Sensitivity to ouabain (10(-4) M) and acetazolamide (5 X 10(-3) M) and dependence on Na+ and K+ in the medium were ascertained. The first system, net chloride influx in ordinary Ringer, exhibited specific ouabain sensitivity and acetazolamide insensitivity. As we have previously shown this system to be clearly dependent on Na+ on the cis and K+ on the trans side, cation dependence was not re-studied. The second system, isoproterenol-stimulated net Cl- outflux, was also ouabain-sensitive and acetazolamide-insensitive. It was dependent on the presence of Na+ on the cis side, but the K+ dependence was less clear. In contrast to the first two, the third system (net influx in low Cl- medium sulfate Ringer containing 2.4 mM Cl-) was largely ouabain-insensitive, completely acetazolamide-sensitive and independent of both Na+ and K+. Thus, the hypothesis of two distinct mechanisms seems to hold for the three active Cl- transport systems in frog skin. Data from various other Cl- transporting epithelia are examined, and the general applicability of such a scheme of categorization for active Cl- transport mechanisms is discussed.
Acetazolamide↗
A blue catalase screening test for pyuria and haematuria.
The blue catalase test is easy to perform and economical of materials. In a series of 529 adult female hospital patients it appeared to be a good screening test for pyuria and haematuria, detecting all but one of the specimens examined with more than 20 red and white cells combined per cubic millimetre of urine and 95.2% of those with more than 10 cells. It indicates a raised leucocyte or red cell excretion rate but is not a test for bacteriuria.
Catalase↗