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M Cohn

Publications and source records attributed to M Cohn.

At least 19 recordsLinked to original sources
PubMed1992

Telomere-associated repeats in Chironomus form discrete subfamilies generated by gene conversion.

In dipteran insects the most distal telomere-associated DNA known to exist consists of long, complex tandem repeats. We have classified the 340-bp tandemly arranged repeats in Chironomus pallidivittatus. The repeats are distributed in a small number of subfamilies. One type of the repeat has the character of a master unit from which other main units can be derived usually by simple changes. The derived subfamilies contain segments that are degenerate versions of the corresponding segment in the master sequence. Such segments can also occur together in one and the same repeat unit in different combinations. There is a complete absence of subfamily-specific base variants in regions lying outside of the degenerate segments. Homogenization takes place between DNA sequences that are often smaller than a whole repeat unit. The mosaic structure of the repeat arrays suggests that gene conversion is an important force in the generation and maintenance of this family of repeats.

Animals↗
PubMed1992

Chromosome ends in Chironomus pallidivittatus contain different subfamilies of telomere-associated repeats.

Tandemly repeated 340 bp sequences, TA repeats, are present in seven of the eight pairs of chromosome ends in Chironomus pallidivittatus, being absent from the telocentric left end of chromosome four. We have previously shown that the family of TA repeats consists of four main subfamilies. One subfamily is composed of a master unit and the other three contain derived units, each of which has a small region where the master sequence is highly mutated. Here we find that there are considerable variations in numbers of TA repeats between animals and for the same telomere in different animals. We also show that the seven telomere pairs containing TA repeats differ with regard to the content of derived subfamilies. The master unit is probably present in all seven pairs. Two of the derived units are exclusively present in two telomere pairs. The third derived unit shows a more irregular distribution. Some of the telomeres have highly variable contents of such units among animals. Subfamilies thus have different behaviour as reflected in their stable and variable patterns of distribution between individual telomeres.

Animals↗
PubMed1992

Is the establishing of tolerance to self obligatorily MHC restricted?

The prevailing paradigm used to interpret how T cells recognize antigen treats antigen processing as obligatory because the T cell antigen receptor complex can only detect antigen located in a "groove" found on MHC-encoded restricting elements. The vast majority of experimental systems used to analyze how T cells recognize antigen depend on induced T cells executing their effector functions, and it is agreed without exception that this event is MHC restricted. However, to date, the extrapolation of the obligatory MHC restriction of effector function to the level of the antigen-responsive T cell that makes the tolerance induction decision, depends not on experiment, but on theoretical constructs. The few experiments designed to test whether tolerance is MHC restricted are open to several interpretations, only one of which is consistent with the view that all antigen recognition events must be MHC restricted. If it can be shown that tolerance is not obligatorily MHC restricted, then the pillar of the prevailing paradigm will have fallen. The experiments described here throw into serious doubt the evidence that has been used to conclude that tolerance is obligatorily MHC restricted.

Animals↗
PubMed1992

What is the selective pressure that maintains the gene loci encoding the antigen receptors of T and B cells? A hypothesis.

The dominant view is that the gene loci encoding the B cell antigen receptor (BAr) or the T cell antigen receptor (TAr) specify a vast array of combining sites. The 'germline' repertoire is estimated to be > 10(10) by multiplying numbers of subunit complements by DN-region variability. This implies that the germline can be maintained by a selection imposed by all or most of the antigenic universe. Its unchallenged popularity, notwithstanding, this neo-germline view is untenable and hence the need for a competing concept, as presented here. The immunoglobulin (Ig) loci are under a totally different selection from the T loci. The Ig loci are selected upon largely by carbohydrate determinants on pathogens that vary more slowly than the proteins produced by the Ig loci, which are necessary to rid these selective antigens. By contrast, the T loci are selected to recognize the allele-specific determinants on restricting elements encoded in the major histocompatibility complex (MHC). The expression of the germline results in a high copy number (HCN) repertoire; this repertoire is the substrate for 'mutation' that yields the low copy number (LCN) repertoire. For the B cell, these two repertoires interact to optimize the response to the unexpected. For the T cell, only the LCN repertoire is functional. The immunoglobulin (Ig) loci are selected upon as light(L)-heavy (H) pairs; the T loci are selected upon as single units alpha or beta (i.e. the VT-gene segments act as a single pool). This competing concept carries with it many important and testable consequences.

Alleles↗
PubMed1992

Improving nursing home care through training and job redesign.

Nursing assistants have the primary contact with older residents of nursing homes. The Penn State Nursing Home Intervention Project's short-term longitudinal study assessed the single and combined effects of two interventions designed to affect nursing assistants' performance by increasing their knowledge and motivation: skills training and job redesign. Statistically significant differences in nursing assistants' knowledge were evident in comparisons between intervention and control sites, but performance was not improved. Implications for policy, practice, and research are discussed.

Evaluation Studies as Topic↗
PubMed1992

Comparison of methods for the determination of unbound triiodothyronine in pregnancy.

OBJECTIVE: To study the changes in unbound T3 concentration in the first trimester of pregnancy. DESIGN: We measured serum unbound T3 concentration before and after termination of pregnancy. PATIENTS: Twenty-six clinically euthyroid women. MEASUREMENTS: We used one non-analogue assay (Sclavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation). RESULTS: Regression analysis did not show any significant agreement between the analogue and non-analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sclavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin. CONCLUSION: We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in pregnancy.

Abortion, Induced↗
PubMed1992

The priming of cytotoxic T-cell precursors is strictly helper T cell-dependent.

Allogeneic chimaeras that utilize C.B-17 SCID mice (H-2d) as recipients of MHC mismatched bone marrow from C57B1/6 (H-2b) or SJL/J (H-2s) mice have been used to provide experimental evidence demonstrating the necessity for a direct interaction between an effector T helper and the cytotoxic T-cell precursor in order to generate cytotoxic effector T cells specific for the minor histocompatibility (H) antigens of DBA/2 (H-2d) mice. No effect of helpers specific for antigen-processed or not-presented on antigen-presenting cells could be observed. Allo-chimaeras that contain T cells bearing H-2s, and which are restricted to H-2d, make a cytotoxic T-cell response to minor H antigens which is H-2d restricted if, and only if, cloned anti-H-2s effector T helpers are present during the in vivo priming step. Cloned anti-H-2d effector helpers, which are without effect in the allo-chimaeras, do provide a strong helper activity when tested in normal H-2d mice. These findings cannot be reconciled with a strict single recognitive model of restrictive antigen recognition, but they are consistent with a dual recognitive model, which incorporates many of the features of the single recognitive model.

Animals↗
PubMed1992

Effect of exercise training on glomerular filtration rate of mice with various degrees of renal mass reduction.

We studied the effect of repeated heavy physical activity on glomerular filtration rate (GFR) in healthy, uninephrectomized and experimentally uremic mice. Exercise consisted of running uphill in the inner surface of a rotating cylinder in ideal environmental temperature. In the control groups, no extra physical activity was imposed. In sham-operated and nephrectomized mice, GFR rose significantly following training. By contrast, GFR did not change significantly in the exercised mice with experimental renal failure 24 h following the last exercise session. During the same period, no significant change was observed in GFR of any of the control groups. Following training in each experimental group, mean aortic blood pressure as well as fractional kidney weight (kidney weight/body weight) were not different from the respective controls. Our results indicate that the capacity to augment GFR by physical training is dependent upon the amount of remaining functional renal tissue.

Animals↗
PubMed1992

Creatine and cyclocreatine effects on ischemic myocardium: 31P nuclear magnetic resonance evaluation of intact heart.

The purpose of this study was to investigate the effects of prior dietary supplementation with creatine (Cr) or cyclocreatine (Cy, a synthetic analogue of Cr) on high energy phosphate metabolism of the ischemic myocardium. To this end, 48 rats were fed the following powdered rat chow diet for 21 days: 16 were fed chow without additives (CON); 16 were fed a diet containing 1% Cr by weight (CR); 16 were fed a diet containing 1% Cy by weight (CY). At the end of the feeding period, rats were anesthetized, hearts harvested and perfused in the Langendorff mode using Krebs-Henseleit buffer (maintained at 37 degrees C, equilibrated with 95% O2/5% CO2) to which 11 mM glucose was added. 31P nuclear magnetic resonance (NMR) studies of myocardial bioenergetics were done using a Bruker AM 500 spectrometer. After acquisition of preischemic spectra, global ischemia was produced by clamping aortic inflow. Ischemia was maintained until adenosine triphosphate (ATP) became NMR invisible (CON = 34 +/- 11 min; CR = 32 +/- 13 min; CY = 56 +/- 13 min; p less than 0.05 CY vs. CR and CON). Half-lives of ATP were 19 min for CON and CR and 37.5 min for CY; half-lives of phosphagen were 4 min for CON and CR and 11 min for CY. Time for return of mechanical function (heart rate x systolic pressure) after ischemia was similar for all three groups (CON = 28 +/- 28, CR = 34 +/- 22, and CY = 22 +/- 15 min), even though the CY group was subjected to longer periods of ischemia). These data indicate that CY, but not CR, pretreatment provides myocardial protection either during and/or after ischemia and allows return of mechanical function after much longer episodes of ischemia than in CON and CR. One factor in the mechanism of protection may be the prolonged maintenance of phosphagen due to the higher equilibrium concentration of phosphocyclocreatine which in turn provides substrate for continued synthesis of ATP during and after ischemia, thus defining Cy as a bioenergetic protective agent. Other mechanisms of protection remain to be defined.

Adenosine Triphosphate↗
PubMed1992

Postnephrectomy mesangial cells secrete a factor(s) that stimulate(s) tubular cell growth in vitro.

Rat kidney mesangial cells were procured from 5 sham-operated and 10 previously uninephrectomized rats. They were grown in cell culture medium supplemented with 20% fetal calf serum. Cell free conditioned medium was collected on the 10th day. Tubular cell cultures were then prepared from 18 normal unoperated 3-week-old rats. Tubular cells from each separate kidney sample were grown in pooled-mesangium conditioned medium from sham-operated or from nephrectomized rats, supplied with 20% pooled serum from either sham-operated or nephrectomized animals. 3H-thymidine incorporation of normal tubular cell cultures grown in nephrectomy mesangium conditioned medium supplemented with sera from nephrectomized animals proved to be significantly greater than that of any of the other three experimental variations. No statistically significant difference was evident when either preconditioned medium of postnephrectomy mesangial cells or postnephrectomy serum were used alone.

Animals↗
PubMed1992

Human chorionic gonadotropin may not be responsible for thyroid-stimulating activity in normal pregnancy serum.

Although hCG can activate thyroid cells in culture there is considerable doubt as to whether it is responsible for the changes in thyroid function which occur during normal pregnancy. Thyroid-stimulating activity (TSA), measured using iodide uptake into FRTL-5 cells, was demonstrated in 32/51 (63%) first and 15/29 (52%) third trimester sera. Free T3 was increased (P less than 0.001) and TSH decreased (P less than 0.01) in first trimester. In the early pregnancy group there was a positive correlation between hCG and TSA (r = 0.594, P less than 0.001) and a negative correlation between hCG and TSH (r = -0.329, P less than 0.02). In third trimester hCG concentration was often below that required to produce TSA in vitro and TSA could not be neutralized by antibodies to hCG. There was no correlation between hCG and TSH or thyroid hormones in the third trimester. In 26 women TSA decreased in parallel with serum hCG concentration after termination of pregnancy (P less than 0.001). Free T3 also decreased (P less than 0.01) and TSH increased (P less than 0.05) after termination. TSA persisted in many patients even after hCG was either very low or undetectable. Purified hCG stimulated iodide uptake in a concentration-dependent manner. Stimulation of iodide uptake by TSH was inhibited by the simultaneous presence of low concentrations of hCG while activity was restored with high concentrations. hCG may contribute to the thyroid changes in early pregnancy. However the poor correlation between TSA and thyroid tests suggests that other factors may be involved. The partial agonist activity of hCG may account for some of the inconsistencies observed but TSA in serum from late pregnancy or after termination of pregnancy is almost certainly due to another hormone or growth factor.

Adult↗
PubMed1992

Inducible transformation of cells from transgenic mice expressing SV40 under lac operon control.

If it were possible to clone in vitro cells of any type, at any stage of differentiation, from an extensively characterized animal such as the mouse, many areas of cell biology would benefit. Indeed, it would be even more helpful if these cells could subsequently be restored to their normal in vivo phenotype whenever required. Here, we describe a step on the pathway to such an idealized "clonable" mouse. In principle, it seeks to link a "universal" transforming agent to a regulatory system that is relatively simple, yet quite foreign to the mouse. A plasmid containing the bacterial lac operator/promoter region linked to the SV40 large T antigen and a vector containing the lac repressor that can be expressed in mammalian cells were coinjected into fertilized mouse oocytes utilizing the standard techniques for generating transgenic mice. Two progeny were obtained that express large T antigen in the presence, but not the absence, of the nonmetabolizable lac inducer, isopropyl-beta-thio-D-galactoside. This report characterizes fibroblast cell lines established from these transgenics that are readily transformed in vitro with isopropyl-beta-thio-D-galactoside. A significant proportion of the cells are restored to their "normal" (nontransformed phenotype) when isopropyl-beta-thio-D-galactoside is removed.

Animals↗
PubMed1991

Evolutionary relations between subtypes of telomere-associated repeats in Chironomus.

Telomere-associated DNA in Chironomus pallidivittatus contains tandemly repeated 340-bp units. We show that they are distributed among several subtypes of which we have characterized two, M1 and D1, with regard to base sequence, homogeneity, and intertelomeric distribution. Each subpopulation is highly homogeneous and the two subtypes have identical consensus sequences throughout 90% of their lengths. In the remaining part the homology is only about 60%. Each subpopulation has its specific intertelomeric distribution and there is no difference in the degree of homogenization within and between telomeres. The repeat unit contains two pairs of subrepeats embedded in linker DNA. This provides a model that makes it possible to relate the two subtypes to each other with regard to evolutionary history. The difference between the two subtypes is due to mutations that have occurred in only one of them, D1, resulting in a decreased similarity between one of its pairs of subrepeats. This type of repeat unit is therefore believed to be derived from the other, M1. The local decrease in similarity between M1 and D1 suggests that homogenization between them occurs by gene conversion.

Animals↗