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Biomedical subjects

C Kemper

Publications and source records attributed to C Kemper.

11 recordsLinked to original sources
PubMed1998

Novel flow cytometry compensation standards: internally stained fluorescent microspheres with matched emission spectra and long-term stability.

In flow cytometry, the emission spectral overlap of fluorescein and R-phycoerythrin is usually corrected by electronic color compensation using microspheres surface labeled with the same fluorochromes. However, the inherent chemical instability of these fluorochromes may cause inaccurate compensation. To overcome these problems, Compen-Flow beads, a new type of compensation standards were developed. The CompenFlow beads are a set of 6.0-microm-diameter polystyrene microspheres that are internally stained with selected BODIPY dye combinations. When excited by the 488-nm argon laser line, these beads show a nearly perfect emission spectral match to fluorescein-stained, R-phycoerythrin-stained and unstained lymphocytes, respectively. Moreover, since the dye molecules are oil soluble, they are contained inside the microsphere matrix instead of merely on the surface; thus, the molecules are shielded from environmental factors that could affect an exposed fluorochrome. Our results show a stable fluorescence spectral profile and constant intensity for at least 2 years stored either refrigerated or at room temperature.

Drug Stability↗
PubMed1998

The complement cofactor protein (SBP1) from the barred sand bass (Paralabrax nebulifer) mediates overlapping regulatory activities of both human C4b binding protein and factor H.

We have previously shown that serum of the teleost fish barred sand bass (Paralabrax nebulifer) cleaves the alpha'-chain of human C4b and C3b. The proteins that participate in these reactions were purified, and a specific protease and a single cofactor protein were identified. Functional characterization of the recombinantly expressed sand bass cofactor protein (SBP1) and truncated forms containing short consensus repeats (SCRs) 1-2, 1-3, 1-4, 1-5, and 12-17 revealed that SBP1 and SCRs 1-4 mediate the functional activities of the human plasma regulatory protein C4bp and factor H. They form a complex with C4b, inhibit the formation, and accelerate the decay of the classical pathway C3 convertase and display cofactor activity for the cleavage of C4b. In contrast, the interaction of SBP1 and SCRs 1-4 with human C3b in all these activities was limited. This difference is due to species-specific incompatibilities between the cofactor protein and human C3b. SBP1 and SCRs 1-5 displayed full binding and cofactor activity for methylamine-treated C3 from trout, a species closely related to the sand bass. The presence of only one cofactor in the fish plasma that combines the functional activities of C4bp and factor H demonstrates that the sand bass cofactor protein is the ancestral precursor to the two complement regulatory proteins in human plasma.

Animals↗
PubMed1998

Ancient origin of human complement factor H.

We studied the evolutionary history of two homologous proteins of the human complement system, factor H (FH) and the alpha chain of the C4b binding protein (C4bpalpha), and included in this study the related proteins from the barred sand bass (P. nebulifer) and the nematode C. elegans. Phylogenetic trees inferred from individual short consensus repeats (SCRs) and divergence among repeats from different genes suggest that human FH has a much closer evolutionary relationship to putative complement components from P. nebulifer and C. elegans than does the C4bpalpha. This indicates that a member of the alternative pathway of the complement system (FH) has an ancient origin, while a homologous member of the classical pathway (C4bpalpha) appeared later in evolutionary history as a result of gene duplication. The ancient evolutionary position of FH is in agreement with the suggestion that the alternative pathway of the complement system is older than the classical pathway. Phylogenetic analysis also shows that the sand bass cofactor protein SBP1 and cofactor related protein SBCRP-1 have diverged very recently.

Amino Acid Sequence↗
PubMed1995

The tolerance for zidovudine plus thrice weekly or daily trimethoprim-sulfamethoxazole with and without leucovorin for primary prophylaxis in advanced HIV disease. California Collaborative Treatment Group.

PURPOSE: Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with HIV infection, but frequent adverse events limit its usefulness. Intermittent dosing and supplementation with leucovorin have been tried in attempts to improve tolerance. We evaluated these strategies in persons with advanced HIV disease. METHOD: One hundred seven patients were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3, and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily (BID); of these, 26 were randomized to leucovorin with each dose. Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week; of these, 27 were randomized to leucovorin with each dose. All patients took zidovudine concurrently. RESULTS: The 24-week risk of discontinuation due to protocol-defined limiting toxicity was 24% with thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95% CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and 59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as headache and gastrointestinal distress, accounted for the observed difference in tolerance between dosing regimens. The 24-week risk of discontinuation due to protocol-defined toxicity was 33% in both the leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to 2.5). The risks of discontinuation for any reason were 53% and 47% (risk ratio 0.8; 95% CI 0.3 to 1.7). CONCLUSION: Intermittent therapy with TMP/SMX BID thrice weekly is better tolerated than daily BID therapy. Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in AIDS, even among patients taking tablets daily.

AIDS-Related Opportunistic Infections↗
PubMed1994

A review of heavy metal and organochlorine levels in marine mammals in Australia.

Study of toxic contaminants in marine mammal specimens collected around Australia is currently uncoordinated and piecemeal. Most states collect samples but there is little or no financial support for their analysis. This study combines data, published or unpublished, from 13 sources. Heavy metals have been analysed in about 676 specimens; over 400 were for mercury levels in P. macrocephalus taken at a whaling station. The remaining samples were mostly from toothed whales, a few baleen whales (< 20), pinnipeds (41) and dugongs (49). The most consistently analysed metals were lead, mercury and cadmium. Liver and kidney lead levels ranged from < 1-3 ppm; levels in bone were 0-418 ppm, with most less than 10 ppm. Mercury levels in a large sample of P. macrocephalus muscle were < 12.2 ppm. Mercury levels in the small number of samples from other species were 0.51-143 ppm (kidney), 1.52-479 ppm (liver) and < 0.1-36 ppm (muscle). Cadmium levels in liver (0-52 ppm) and kidney (0-106 ppm) were extremely variable. Levels greater than 10 ppm were recorded in many species and were especially high in Hydrurga leptonyx, Dugong dugon, Mesoplodon layardii and Pseudorca crassidens. Adult Tursiops truncatus inhabiting the inshore gulfs of South Australia had considerably higher levels of cadmium compared with other regions. Information on organochlorine levels is sparse (approximately 39 specimens) and suggest low levels when compared to other parts of the world. Total DDT was highest (28.4 ppm) in a neonatal Orcinus orca. Some high levels of DDT were recorded in Tursiops truncatus, Delphinus delphis and Arctocephalus pusillus doriferus. PCBs ranged from < 0.05 to 3.87 ppm. A comprehensive pathological assessment of marine mammals is needed in order to evaluate the effects of toxic contaminants.

Animals↗
PubMed1992

Length of stay and survival after intensive care for severe Pneumocystis carinii pneumonia. A prospective study. California Collaborative Treatment Group.

Survival rates for persons receiving intensive care for Pneumocystis carinii pneumonia have improved. However, the utility of prolonged intensive care for patients who do not show initial improvement remains unclear. We assessed survival in a nested cohort study of patients receiving intensive care while participating in a randomized trial of early adjunctive corticosteroids for Pneumocystis pneumonia. Twenty-eight of 251 (11 percent) participants were admitted to an intensive care unit. Fourteen (50 percent) of these were discharged alive from the intensive care unit and 11 (39 percent) were discharged alive from the hospital. Survivors and nonsurvivors were similar demographically and with respect to treatment received but differed in the mean days of intensive care received (4.5 vs 8.6 [p = 0.02]). The conditional probability surviving to hospital discharge after intensive care dropped steadily from 39 percent at intensive care unit admission to 17 percent after one week and to 0 percent after two weeks.

Adrenal Cortex Hormones↗
PubMed1990

A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.

BACKGROUND: Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial. METHODS: A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy. RESULTS: Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms. CONCLUSIONS: Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Prevention of neural myoinositol depletion in diabetic rats by aldose reductase inhibition with tolrestat.

The effect of the aldose reductase inhibitor tolrestat on the sugar and polyol contents in the sciatic nerve was investigated in male Wistar and Sprague-Dawley rats rendered diabetic with streptozocin. At a daily oral dose of 5 mg/kg, given for 10 days before and for 14 days after streptozocin injection, tolrestat completely prevented the accumulation of sorbitol and the depletion of myoinositol.

Aldehyde Reductase↗
PubMed1985

Experimental carbon dioxide laser brain lesions and intracranial dynamics: Part 1. Effect on intracranial pressure, systemic arterial pressure, central venous pressure, electroencephalography, and gross pathology.

Experimental brain lesions were created in the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy (40-watt impacts of 0.5-second duration for a total of 4 seconds on a 12.5-mm surface). Behavior, intracranial pressure (ICP), systolic arterial pressure (SAP), central venous pressure (CVP), electroencephalography (EEG), and gross pathology were studied at 2, 6, and 24 hours after the insult at a constant PaCO2 (38-42 torr). Disruption of the blood-brain barrier (Evans blue extravasation) was uniformly seen extending from the impact crater into the surrounding white matter in all groups. The ICP was elevated in sham-operated animals at 2 hours after the impact, and it remained elevated at 6 and 24 hours. The EEG revealed severe slowing with high voltage waves in the insulted left hemisphere. There was no change in mean SAP or CVP when compared to the sham-operated group. In the dexamethasone-pretreated group, there was a reduction of ICP when compared to the untreated group at 24 hours after the insult (P less than 0.005), but no changes in the gross pathology were noted.

Animals↗
PubMedDate not supplied

Cloning and recombinant expression of a barred sand bass (Paralabrax nebulifer) cDNA. The encoded protein displays structural homology and immunological crossreactivity to human complement/cofactor related plasma proteins.

A new cofactor related cDNA in the bony fish Paralablax nebulifer, (barred sand bass) was isolated from a sand bass liver cDNA library. The clone (c71) is 1040 bp in size and the predicted translation product of 204 amino acids contains a hydrophobic signal peptide, which is followed by a region of three short consensus repeats (SCRs). The three SCRs display high homology to SCRs of the 110 kDa chain of the sand bass plasma cofactor protein, and to a lesser degree to human complement factor H related protein 3 (FHR-3) and to human factor H. Recombinant expression of the c71 cDNA in the baculovirus system shows a product of an apparent molecular mass of 27 kDa, which is secreted and glycosylated. It also contains a His-tag for purification purposes. Removal of the His-tag yields a 24 kDa protein, and deglycosylation further reduces the molecular mass to 21 kDa. This size is in agreement with the calculated molecular mass based on amino acid composition. The sand bass SBCFR-1 protein is immunologically related to the human complement proteins, factor H and factor H-related protein 3. The recombinantly expressed protein reacted with antisera against the human FHR-3 protein and SCRs 19-20 of human factor H. The presence of SCR-containing proteins in sand bass plasma and their structural and immunological homology to human FHR-3 and factor H suggests for a common function between these evolutionary related proteins.

Amino Acid Sequence↗