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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 595 records · Page 33Linked to original sources
PubMed1988

The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets.

Stem cell Ag 1 and 2 (Sca-1 and Sca-2), so named due to their expression by mouse bone marrow stem cells, were evaluated for expression by populations of cells within the thymus. Immunohistochemical analysis demonstrated that Sca-1 was expressed by cells in the thymic medulla and by some subcapsular blast cells, as well as by the thymic blood vessels and capsule. Sca-2 expression, which was limited to the thymic cortex, could be associated with large cycling thymic blast cells. Both Sca-1 and Sca-2 were expressed on a sub-population of CD4-CD8- thymocytes, and this subpopulation was entirely contained within the Ly-1lo progenitor fraction of cells. Sca-1 expression by a phenotypically mature subset of CD4+CD8- thymocytes was also noted. Conversely, Sca-2 expression was observed on a phenotypically immature or nonmature subpopulation of CD4-CD8- thymocytes. MEL-14, an antibody that defines functional expression of a lymphocyte homing molecule, identified a small population of thymocytes that contained all four major thymic subsets. Sca-2 split the MEL-14hi thymocyte subset into two Sca-2+ non-mature/immature phenotype fractions and two Sca-2- mature phenotype fractions. In peripheral lymphoid organs, Sca-1 identified a sub-population of mature T lymphocytes that is predominantly CD4+CD8-, in agreement with the thymic distribution of Sca-1. Peripheral T cells of the CD4-CD8+ phenotype were predominantly Sca-1-. In contrast, Sca-2 did not appear to stain peripheral T lymphocytes, but recognized only a subset of B lymphocytes which could be localized by immunohistochemistry to germinal centers. Thus, expression of Sca-1 is observed throughout T cell ontogeny, whereas Sca-2 is expressed by some subsets of thymocytes, including at least one half of thymic blasts, but not by mature peripheral T lymphocytes.

Animals↗
PubMed1988

MHC polymorphism pre-dating speciation.

Two features distinguish the polymorphism of the major histocompatibility complex (MHC) loci from that of other loci: its high diversity and the large genetic distance between MHC alleles. More than 100 alleles exist in natural populations in the mouse at each of the functional class I and class II alleles, all alleles occurring at frequencies that cannot be explained by recurrent mutations. Some of the alleles differ by approximately 70 nucleotides in the coding region alone and some of the products of the allelic genes differ by more than 50 amino acids. It has generally been assumed that these differences accumulated after species inception. Here, we present evidence for an alternative explanation of the origin of MHC polymorphism: a large part of the MHC polymorphism pre-dates speciation and is passed on from species to species. We describe allelic differences that must have arisen before the separation of mice and rats from a common ancestor more than 10 million years ago.

Alleles↗
PubMed1988

Subacute cutaneous lupus erythematosus. Clinical, serologic, immunogenetic, and therapeutic considerations in seventy-two patients.

We studied 72 patients with subacute cutaneous lupus erythematosus (SCLE). Forty-nine of the patients had been part of an earlier study. The cutaneous disease was primarily annular in 17 patients, papulosquamous in 48, and a combination in 7. Although the major feature of SCLE is nonscarring, non-atrophy-producing lesions, scarring discoid lesions were observed in 21 patients. Thirty-six patients fulfilled criteria for systemic lupus erythematosus. Cytoplasmic antibodies were present in only 22 patients. However, in the group of 23 patients recently analyzed, 13 of 22 tested had anti-Ro (SS-A) and/or anti-La (SS-B). HLA-DR3 was present in 22 of 59 patients. Neither anti-Ro (SS-A) nor HLA-DR3 correlated with any clinical finding. Forty-seven patients have had continued activity of their disease, but in most patients, the disease has been controlled with sunscreens, topical and intralesional corticosteroids, and oral hydroxychloroquine. A broad spectrum of systemic lupus erythematosus-associated phenomena can occur in patients with SCLE. The disease is frequently easily controlled, and may become quiescent. This subset of lupus patients is less distinctive than has been previously suggested.

Adrenal Cortex Hormones↗
PubMed1988

Technical and statistical improvements for flow cytometric DNA analysis of paraffin-embedded tissue.

Flow cytometric DNA analysis of paraffin-embedded solid tumors has permitted review of large series of archival tissue in attempts to relate abnormal DNA content to prognosis. Limitations of the technique include: 1) a laborious, time-consuming procedure; 2) variation in technique between laboratories; and 3) lack of an objective method of computing DNA indices. Critical evaluation of our technique has shortened the time involved in dewaxing and rehydration, selectively utilized patient's own normal tissue as the internal standard, proved reproducibility of stored specimens, standardized DNA index computation, and developed a statistical analysis to confirm aneuploidy. These technical improvements and the development of a statistical analysis provide a way to shorten the procedure time and standardize the data generated from flow cytometric DNA analysis so as to improve the quality of retrospective reviews of paraffin-embedded tumors and accelerate the definition of flow cytometry's role as a prognostic indicator.

Breast Neoplasms↗
PubMed1988

T cell response to myoglobin: a comparison of T cell clones in high-responder and low-responder mice.

Mice carrying the H-2b haplotype (e.g., inbred strains C57BL/6 and C57BL/10) are low responders to sperm whale myoglobin when tested in the T cell proliferation assay. Their response is improved by the removal of the Ly-2+ cells from the lymph node population, but it still remains significantly lower than that of cells cells from high-responder strains (e.g., DBA/2, H-2d). To determine whether T cells from the low and high-responder mice recognize the same or different epitopes on the immunizing antigen, we obtained sets of T cell clones from both strains and tested them against peptides representing different regions of the myoglobin molecule, as well as against myoglobins from species other than the sperm whale. Four types of T cell clones were obtained from the DBA/2 mice: 3 types responded to the peptide 107-120 (9 clones altogether), and 1 type responded to the peptide 133-149 (4 clones altogether). The 3 types responding to the peptide 107-120 could be distinguished by their response to horse myoglobin or by the restriction of the response (Ad vs. Ed). Similarly, 5 types of T cell clones were obtained from the C57BL/6 mice: 2 types responded to the peptide 10-22 (1 type, but not the other, responded to horse myoglobin); 1 type responded to the peptide 133-149; and 2 types did not respond to any of the peptides used (1 type, but not the other, responded to dog myoglobin). All 5 types (13 clones altogether) were presumably Ab restricted. These results demonstrate the diversity of epitopes in single antigenic regions and show equivalent heterogeneity of T cell repertoires in high and low responder mice. Attempts to demonstrate specific T cell suppression in the low responder mice failed; only partial, nonspecific suppression was observed.

Animals↗
PubMed1988

Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution.

To obtain an insight into the evolutionary origin of the major histocompatibility complex (MHC) class I polymorphism, a cDNA library was prepared from a heterozygous chimpanzee cell line expressing MHC class I molecules crossreacting with allele-specific HLA-A11 antibodies. The library was screened with human class I locus-specific DNA probes, and clones encoding both alleles at the A and B loci have been identified and sequenced. In addition, the sequences of two HLA-A11 subtypes differing by a single nucleotide substitution have been obtained. The comparison of chimpanzee and human sequences revealed a close similarity (up to 98.5%). The chimpanzee A locus alleles showed greatest similarity to the human HLA-A11/A3 family of alleles, one of them being very close to HLA-A11. Similarly, segments of the ChLA-B alleles displayed greatest similarity to certain HLA-B alleles. The calculated evolutionary branch point for the A11-like alleles is 7 x 10(6) to 9 x 10(6) years, whereas the other A locus alleles diverged between 12 x 10(6) and 17 x 10(6) years ago. Since the human and chimpanzee lineages separated 5 x 10(6) to 7 x 10(6) years ago, our data support the notion that during evolution, MHC alleles are transmitted from one species to the next.

Alleles↗
PubMed1988

Mapping of the Sod-2 locus into the t complex on mouse chromosome 17.

A human DNA probe specific for the superoxide dismutase gene was used to identify the corresponding mouse gene. Under the chosen hybridizing conditions, the probe detected DNA fragments most likely carrying the mouse Sod-2 gene. Mapping studies revealed that the Sod-2 gene resides in the proximal inversion of the t complex on mouse chromosome 17. All complete t haplotypes tested showed restriction fragment length polymorphism which is distinct from that found in all wild-type chromosomes tested. The Sod-2 locus maps in the same region as some of the loci that influence segregation of t chromosomes in male gametes. The possibility that the Sod-2 locus is related to some of the t-complex distorter or responder loci is discussed. The data indicate that the human homolog of the mouse t complex has split into two regions, the distal region remaining on the p arm of human chromosome 6, while the proximal region has been transposed to the telomeric region of this chromosome's q arm.

Animals↗
PubMed1988

The forgotten surgical foreign body.

Instruments and drains left in the abdomen following surgery may be responsible for bizarre and varied complications. The patient may remain asymptomatic for months or even years. Complications include adhesion formation, intestinal obstruction, abscesses, and erosion into the gastrointestinal tract. We report 3 patients in whom retained surgical material eroded into the duodenum and colon, respectively, and produced unusual radiologic findings and complications.

Adult↗
PubMed1988

The prognostic value of the exercise test.

Numerous investigators have demonstrated that responses to exercise testing enable prediction of the severity of underlying coronary disease and the patient's prognosis. However, exercise testing cannot predict angiographic findings or a poor prognosis with absolute certainty. Because survival can only be improved in specific clinical subsets of patients, it is important to carefully select for catheterization those in whom intervention can improve both quality and quantity of life. To deliver cost-effective health care, an effort has been made to use decision analysis to select those who should undergo cardiac catheterization. Decision analysis depends on reliable information regarding the predictive accuracy of the exercise test. Thus, this review is timely. Recent studies investigating the prognostic value of the exercise test are reviewed in this monograph. Patients include those recovering from a recent myocardial infarction (MI), those with stable coronary heart disease (including studies that have considered coronary angiographic findings, cardiac end points, and/or improved survival with coronary artery bypass surgery), and apparently healthy individuals. From this review, we conclude that silent ischemia induced by exercise testing in apparently healthy men is not as predictive of a poor outcome as once thought. Also, the use of the exercise test for screening is even more misleading than previously appreciated because of the higher rate of false positive results. Review of the 24 available studies of exercise testing in post-MI patients demonstrates that clinical judgment can be used to identify the high-risk patients, and that ST-segment shifts are not as predictive of high risk as an abnormal systolic blood pressure response or a poor exercise capacity. In patients with stable coronary heart disease, studies considering angiographic findings, cardiac events, and the differential outcome of coronary artery bypass surgery as compared with medical therapy have shown the exercise test to have prognostic power. From this perspective, it is obvious that there is much information supporting the use of exercise testing as the first noninvasive step after the history, physical examination, and resting electrocardiogram in the prognostic evaluation of patients with coronary artery disease. It accomplishes both purposes of prognostic testing: to provide information regarding the patient's status, and to help make recommendations for optimal management. The exercise test results help us make reasonable decisions for selection of patients who should undergo coronary angiography-including quality-of-life issues.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1988

The dissociation between aminoglycoside serum concentrations and nephrotoxicity.

Using newborn and adult rats we tested the correlation between aminoglycoside dose, resultant serum and renal cortical concentrations and nephrotoxicity evidenced by creatinine in serum and urine, N-acetylglucosaminidase and beta 2 microglobulins in urine and sphingomyelinase in renal cortical tissue. Our data reveal that aminoglycoside nephrotoxicity is clearly more evident in adult rats despite significantly lower drug serum concentrations and in the presence of substantially higher renal cortical concentrations. These data indicate that high aminoglycoside serum concentrations are not causing nephrotoxicity but rather reflect secondary body accumulation of the drug associated renal damage.

Acetylglucosaminidase↗
PubMed1988

Pharmacokinetics and adverse effects of amphotericin B in infants and children.

The pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug for proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 microgram/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were greater than 0.3 microgram/ml throughout the 24-hour period, and in 12 of 13 patients were greater than 0.5 microgram/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 +/- 1.5 hours (mean +/- SEM), clearance rate 26 +/- 5 ml/kg.hr, and distribution volume 378 +/- 25 ml/kg. The half-life inversely correlated with patient's age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.

Adolescent↗
PubMed1988

Mhc class II DNA polymorphisms within and between chromosomal species of the Spalax ehrenbergi superspecies in Israel.

Restriction fragment length polymorphisms (RFLPs) of two major histocompatibility class II genes (P alpha 1 and Q beta) were studied in 13 populations of four chromosomal species (2n = 52, 54, 58 and 60) of the mole rat, Spalax ehrenbergi superspecies in Israel. A substantial frequency of allelic fragments was found in both genes for all populations, including a desert isolate. In the P alpha 1 gene, one allelic fragment is a result of a deletion mutation which is diagnostic of the 2n = 52 chromosomal species. All other ten allelic variants are the result of point mutations. All mutations are located in a short region flanking the 3' end of the gene. Based on Mhc polymorphisms we confirm earlier evidence that gene flow does not occur between the older chromosomal species (2n = 52, 54, 58), and that reproductive isolation decreases, progressively from the oldest to the youngest species (2n = 60).

Animals↗
PubMed1988

t-Specific DNA polymorphisms among wild mice from Israel and Spain.

Lehrach and his coworkers have isolated a series of DNA probes that specifically hybridize with different regions of mouse chromosome 17 within the t complex. The probes display restriction fragment length polymorphisms, RFLPs, which are specific for the t haplotypes in all laboratory mouse strains tested thus far. Some of these probes have been used to test wild mice populations for these t-associated DNA forms. It is demonstrated that populations from Germany, Switzerland, Italy, Greece, Yugoslavia, Australia, Costa Rica, and Venezuela contain chromosomes in which all the tested DNA loci display the t-specific polymorphisms. The frequency of mice carrying these chromosomes is as high as 31%. Wild mice from Israel and Spain, on the other hand, carry chromosomes displaying t-specific DNA forms only at one or two of the probed loci, while the other loci carry the wild-type (+) forms. These chromosomes thus resemble the partial t haplotypes known from the study of laboratory mice. One possible interpretation of these findings is that these DNA polymorphisms contributed to the assembly of the complete t haplotypes and that these haplotypes may have originated in the Middle East.

Animals↗
PubMed1988

Exercise-induced hypotension in a male population. Criteria, causes, and prognosis.

The objective of this study was to demonstrate the causes, optimal definition, and predictive value of exercise-induced hypotension occurring during treadmill testing. This study included all patients referred for clinical reasons to the Long Beach Veterans Administration Medical Center treadmill laboratory and then followed for a 2-year period for cardiac events. The population consisted of 2,036 patients who underwent testing from April 4, 1984, to May 7, 1987, 131 of whom exhibited exercise-induced hypotension (6.4%). We found that exercise-induced hypotension is usually related to myocardial ischemia or myocardial infarction, is best defined as a drop in systolic blood pressure during exercise below the standing preexercise value, and indicates a significantly increased risk for cardiac events (3.2-fold, p less than 0.005). This increased risk was not found in those having no previous myocardial infarction or no signs or symptoms of ischemia during the exercise test, and the increased risk was also not found in those undergoing a treadmill test within 3 weeks after a myocardial infarction. Exercise-induced hypotension appeared to be reversed by revascularization procedures, but confirmation of a beneficial effect on survival requires a randomized trial. The clinical importance of this study is that we have demonstrated that a drop in systolic blood pressure below standing preexercise values during treadmill testing indicates an increased risk for cardiac events except in certain subsets of patients.

Adult↗
PubMed1988

Comparison of the digitalis receptor in erythrocytes from preterm infants and adults.

We compared 86rubidium by erythrocytes of preterm infants and adults as a measurement of their Na+, K+, ATPase enzyme system. In neonates, total uptake (0.92 +/- 0.13 micrograms/10(6) cells) and specific uptake (0.64 +/- 0.076 micrograms/10(6) cells) were significantly higher than in adults (0.52 +/- 0.1 and 0.29 +/- 0.06 micrograms/10(6) cells, respectively; p less than 0.025). The percentage of specific uptake from total uptake was higher in infants (73.3 +/- 2.3%) than in adults (57.9 +/- 4.6%) (p less than 0.005). No differences were found in the affinity constant of 86Rb uptake between infants (4.35 +/- 0.48 ng/ml) and adults (4.85 +/- 0.48 ng/ml). Stratification of infants according to their serum K+ concentrations revealed that levels above 5.4 mEq/liter were associated with a higher specific uptake (0.79 +/- 0.107 micrograms/10(6) cells) than in normokalemic infants (0.54 +/- 0.09 micrograms/10(6) cells) or adults (0.304 +/- 0.061 micrograms/10(6) cells) (p less than 0.05). The difference between hyperkalemic and normokalemic infants persisted after excluding those who received adult packed cells (0.88 +/- 0.1 and 0.6 +/- 0.12 micrograms/10(6) cells, respectively) (p less than 0.05). Infants with serum K+ greater than 5.8 mEq/liter received on average significantly more K+ in previous days (2.46 +/- 0.49 versus 1.13 + 0.34 mEq/kg.day; p less than 0.025). The different K+ level could not be attributed to different creatinine clearance in the two groups.

Adult↗