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J K Thomas

Publications and source records attributed to J K Thomas.

At least 19 recordsLinked to original sources
PubMed2000

Distinct categories of immunologic changes in frail elderly.

Immune changes and their relationships in a frail elderly population (N=116, age 70-103, median 86 years) were defined in comparison to a healthy younger group. Previous immune studies in the elderly have generally focused on one or few parameters without correlation analyses. Furthermore, the study populations have been active elderly in relatively small numbers. A total of 33 immune parameters representing many aspects of the immune system were quantified. Most changes in the frail elderly were parallel to those reported in active elderly. A classification tree analysis revealed that increased plasma activation markers (neopterin and sTNF-R) and increased CD28 expression on CD8 T cells and proliferative response separated the aged and control populations. Statistical procedures utilizing principal components analyses, partial correlations and exploratory factor analyses all indicated that immunologic parameters in frail elderly are grouped in three major clusters of immunologic results. These involved (a) increased plasma levels of neopterin and sTNF receptor indicating elevated IFNgamma and TNF cytokine activity; (b) increased proportion of mature (CD45RO) versus naïve (CD45RA) T cells; and (c) a diverse group of related changes including impaired proliferative response, reduced T cells, CD28 and CD25 expression, B cell percentage and lower CD4:CD8 ratios and increased HLA-DR expression. These findings emphasize that several different groups of immune parameters but not 33 independent immune changes, occurred in the aged population.

ADP-ribosyl Cyclase↗
PubMed1998

Thoracic splenosis.

Thoracic splenosis is a rare pathologic entity resulting from seeding of splenic tissue in the pleural cavity after thoracoabdominal trauma. A 45-year-old man with a history of splenectomy secondary to abdominal trauma presented with a left lung mass and an inconclusive tissue diagnosis after needle biopsy. Thoracic splenosis was not suspected preoperatively, considered on an intraoperative frozen section, and established on permanent pathologic biopsy specimens obtained during thoracotomy. A history of thoracoabdominal trauma, combined with radiologic and radionuclide imaging studies, may establish the diagnosis without thoracotomy.

Abdominal Injuries↗
PubMed1998

Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy.

The selection of bacterial resistance was examined in relationship to antibiotic pharmacokinetics (PK) and organism MICs in the patients from four nosocomial lower respiratory tract infection clinical trials. The evaluable database included 107 acutely ill patients, 128 pathogens, and five antimicrobial regimens. Antimicrobial pharmacokinetics were characterized by using serum concentrations, and culture and sensitivity tests were performed daily on tracheal aspirates to examine resistance. Pharmacodynamic (PD) models were developed to identify factors associated with the probability of developing bacterial resistance. Overall, in 32 of 128 (25%) initially susceptible cases resistance developed during therapy. An initial univariate screen and a classification and regression tree analysis identified the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC[0-24]/MIC) as a significant predictor of the development of resistance (P < 0.001). The final PK/PD model, a variant of the Hill equation, demonstrated that the probability of developing resistance during therapy increased significantly when antimicrobial exposure was at an AUC[0-24]/MIC ratio of less than 100. This relationship was observed across all treatments and within all organism groupings, with the exception of beta-lactamase-producing gram-negative organisms (consistent with type I beta-lactamase producers) treated with beta-lactam monotherapy. Combination therapy resulted in much lower rates of resistance than monotherapy, probably because all of the combination regimens examined had an AUC[0-24]/MIC ratio in excess of 100. In summary, the selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUC[0-24]MIC ratio of less than 100.

Acute Disease↗
PubMed1997

Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various beta-lactam antibiotics.

OBJECTIVE: To determine the propensity of beta-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: Two open, randomized, double-blind, parallel-group studies were conducted in young, healthy, male volunteer subjects. Using a common protocol, 24-hour urine collections were analyzed for the renal tubular enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied included gentamicin plus placebo and gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobial regimens were administered for 7 days. Eight subjects completed each treatment group. RESULTS: There were no significant differences between treatment groups with regard to urine creatinine excretion or serum gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate treatment compared with that in the gentamicin plus placebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ceftazidime treatment (p < 0.05) compared with the other two treatments. CONCLUSIONS: Based on relative enzymuria, ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP and NAG reflect insults to the kidney, these studies suggest that ceftazidime may enhance aminoglycoside-induced renal injury. Piperacillin had no effect on enzymuria and would appear not to enhance or protect against aminoglycoside-induced renal injury.

Acetylglucosaminidase↗
PubMed1996

HIV disease in children is associated with a selective decrease in CD23+ and CD62L+ B cells.

We characterized the surface phenotype of B cells from HIV+ children in order to better understand the biology of B cell dysregulation. Twenty-nine HIV-infected, twenty-one exposed, and nineteen age-matched control children were studied for expression of CD5, CD10, CD21, CD23, CD25, CD62L, CD71, and CD69. We conclude that, despite persistent high immunoglobulin levels, total B cells decreased as HIV disease progressed, with selective decreases in CD62L+ and CD23+ B cells. This resulted in an increased proportion of usually minor subpopulations of CD62L- and CD23-negative B cells. We did not find significantly altered B cell expression of other activation/immaturity antigens. This suggests an absolute decrease in a subset of antigen-responsive B cells and a disproportionate increase in a subset of hyperstimulated B cells. These findings provide a biological basis for the paradoxical generalized B cell hyperactivity and specific immune unresponsiveness that are characteristic of HIV infection in children.

Antigens, CD↗
PubMed1985

Effects of nitrogen mustard on potassium transport systems and membrane structure of Ehrlich ascites tumor cells.

By Ehrlich ascites tumor cells 86Rb+ has been shown to be a suitable tracer for K+-transport. Sixty percent of the total 86Rb-uptake into these cells is ouabain-inhibitable, 30% is sensitive to furosemide and 10% enters the cells by ouabain and furosemide-insensitive systems. N-Mustard inhibits both the ouabain-sensitive and the furosemide-inhibitable systems. The uptake which is resistant to both inhibitors is not affected by the alkylating drug. At N-mustard concentrations below 10 microM, the reduction of the Rb-uptake is predominantly due to the inhibition of the furosemide-sensitive transport. Higher concentrations are required before a significant inhibition of the ouabain-sensitive transport can be observed. The dose response curve of the furosemide-sensitive transport--not, however, of the ouabain inhibitable pump--corresponds to the dose response curve for the antiproliferative activity of N-mustard. The recovery of the furosemide-sensitive transport after a single exposure to N-mustard is relatively slow and--in contrast to the repair of DNA cross-links--is characterized by an initial 4-hr lag period. Furosemide alone does not interfere with cell multiplication. The inhibition of the transport system alone does, therefore, not explain the antitumor activity of N-mustard. The effect is discussed as a marker for membrane lesions after exposure to alkylating agents. In order to investigate the influence of N-mustard on membrane structure, membranes were labelled with diiodofluoresceiniodoacetamide. Anisotropy curves obtained from time-dependent depolarization of delayed fluorescence indicated a mustard induced immobilization of membrane constituents. Lateral diffusion of lipophilic probes was determined by following the quenching of fluorescence of pyrene by cetylpyridinium. The latter studies yielded no evidence for a change in membrane lipid fluidity. The data are interpreted as the results of cross-links of membrane proteins by the bifunctional alkylating agent.

Animals↗
PubMed1980

Interaction of lysophosphatidylcholine with phosphatidylcholine bilayers. A photo-physical and NMR study.

Several photo-physical methods together with 31P-NMR have been used to investigate the effect of lysophosphatidylcholine on phosphatidylcholine bilayers. 31P-NMR shows that the permeability of the vesicle to Eu3+ increases sharply above approx. 40% lysophosphatidylcholine: fluorescence-quenching studies also show this type of behavior. Similar sharp changes in vesicle properties are observed via the photo-physical technique at this lysophosphatidylcholine/phosphatidylcholine composition. Fluorescence spectra of pyrene and pyrene carboxaldehyde show that increasing lysophosphatidylcholine composition increases the polarity of the environments of these probes up to 40% lysocompound. Above this composition the photo-physical properties of the probes slowly revert to those characteristic of the micellar lyso-compound. The pyrene fluorescence lifetime, the fine structure of the fluorescence, and the case of formation of pyrene excimer in these bilayer mixtures suggest that pyrene complexes weakly with the charged nitrogen of the choline group of the phosphatidylcholine and that the physical state of the system has a striking effect on this complexation process. Similar experiments with simple quaternary compounds lend strong support to this suggestion. The studies monitor in several ways the effect of bilayer composition on movement of molecules in these systems. The degree or site of solubilization of carcinogens is also uniquely affected by composition.

Kinetics↗
PubMed1979

Comparative studies of the physical state of the lipid phase of normal and hypercholesterolemic very low density lipoprotein.

Very low density lipoproteins (VLDL) were prepared from the serum of rabbits at various stages of hypercholesterolemia (95--1665 mg cholesterol/100 ml of serum). The most notable chemical change in hypercholesterolemic (hc) VLDL was the greatly increased content of cholesteryl esters and the greatly decreased content of triglycerides, compared to normal (n) VLDL. Structurally, the lipid region of n VLDL possessed a much lower microviscosity than did hc VLDL, when analyzed by fluorescence polarization and pyrene eximer methods. The microviscosity of the redispersed n VLDL lipid extract was considerably greater than the observed in n VLDL; but less than that of hc VLDL. Incorporation of pyrene into the lipid region of n VLDL and hc VLDL allowed assessment of various properties of the surface and hydrocarbon regions of these lipoproteins. Only slight differences were found in the pyrene monomer 3 : 1 fluorescence emission peak ratios, and in the rate constant for quenching of pyrene by O2. However, the quenching rate constant of pyrene by I- and iodoheptane were different for each lipoprotein.

Animals↗
PubMed1976

The study of rous sarcoma virus-transformed baby hamster kidney cells using fluorescent probes.

The fluorescent probes pyrene, pyrene butyric acid and N-phenyl 1-naphthylamine have been used to investigate the changes that accompany in vitro transformation of a baby hamster kidney cell line using Rous sarcoma virus. The fluorescent probes which reside in the membrane were used to compare the changes in microviscosity and polarity of the membranes of normal cells with two transformed cell lines. The spectrofluorimetric data indicate that following transformation the probe N-phenyl 1-naphthylamine resides in a more polar environment. However, using the probe pyrene, the yield of excimer indicates decreased mobility of this probe in the membrane of transformed cells. The data also indicate differences between the two transformed cell lines. Laser photolysis was used to study the lifetime of the pyrene probes and the quenching of the pyrene fluorescence in the membrane by several different quenching molecules. The data indicate differences between the three cell lines and suggest that transformation decreases movement within the membrane.

1-Naphthylamine↗
PubMed1976

Kinetic processes in Escherichia coli membranes and cells. A laser photolysis study using derivatives of pyrene.

Pyrene and several derivatives of pyrene are used to investigate photo-induced kinetic processes in whole cells and membranes extracted from Escherichia coli. A mutant of E. coli was used which, under appropriate growth conditions, produced a complete or incomplete lipopolysaccharide in the outer membrane. The pyrene derivatives used were: pyrene sulfonic acid, pyrene butyric acid and the ester of pyrene butyric acid and 10-hydroxydecanoic acid. The pyrene chromophore was excited by the ultraviolet pulse from a Q switch, frequency-doubled, ruby laser. The lifetimes of the pyrene fluorescence in the presence of the quenchers O2, thallous ion (T1+), I-and CH3NO2 were measured and tabulated as second order rate constants. For the most part the quenching rate constants were much lower than the corresponding values observed in simple nonviscous solution, e.g. ethanol. This is interpreted as being due to the location of the probe within the membrane. The membrane inhibits the movement of the quenchers to the excited state. Cell membranes containing complete lipopolysaccharide showed significantly lower quenching rates for the probes pyrene and pyrene sulfonic acid than cell membranes with incomplete lipopolysaccharide. From an amalysis of the kinetic data it is suggested that pyrene and pyrene sulfonic acid are located near and under lipopolysaccharide and close to membrane proteins. On the other hand, no effect of lipopolysaccharide composition was observed for the probes pyrene butyric acid and pyrene butyroyl decanoic acid. This may suggest that these probes are located primarily in the lipid part of the membrane. A simple model for the outer membrane of E. coli is suggested that accounts for the observed laser-induced kinetic processes.

Biological Transport↗
PubMed1976

Effect ofcholinergic ligands on the lipids of acetylcholine receptor-rich membrane preparations from Torpedo californica.

Ion permeation, triggered by ligand-receptor interaction, is associated with the primary events of membrane depolarization at the neuromuscular junction and synaptic connections. To explore the possible sites of ion permeation, the long-lived fluorescent probe pyrene (fluorescence lifetime approximately 400 nsec) has been inserted into the lipid phase of acetylcholine receptor-rich membrane (AcChR-M) preparations from Torpedo californica. The pyrene probe is susceptible to both fluidity and permeability changes in the lipid bilayer. These changes are detected by variations in the rate of decay of the excited singlet state of pyrene after pulsation with a 10-nsec ruby laser flash. Variations of these lifetimes in the membrane preparations alone or in the presence of quenchers show that binding of cholinergic agonists and antagonists, neurotoxins, and local anesthetics to AcChR-M produces varying effects on the properties of the pyrene probe in the lipid phase. It is concluded that binding of cholinergic ligands to the receptor does not significantly alter the fluidity of permeability of the lipids in the bilayer contact with pyrene. On the other hand, local anesthetics do affect these properties.

Acetylcholine↗