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Biomedical subjects

P Kramer

Publications and source records attributed to P Kramer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inhibin and oestradiol-17 beta in antral follicles of various size classes of cyclic rats.

On the various days of the 5-day oestrous cycle of the rat, ovarian antral follicles were dissected out and grouped in five size classes. Four follicles of the same size class were homogenized jointly in medium, after which inhibin-like bioactivity, inhibin immunoreactivity and oestradiol-17 beta content were measured. In general, there was a significant correlation between immunologically and biologically active inhibin levels in the different size classes; overall correlation was 0.85 (n = 87, P < 0.00001). In the smallest antral follicles (classes 1 and 2) inhibin bioactivity was detected only during the first three days of the cycle. With increasing follicle size, inhibin bioactivity and immunoreactivity increased, with maximal activity present in the largest, i.e. preovulatory, follicles (class 5) during the last three days of the cycle (the day of oestrus denotes day 1 of the cycle). These results indicate that only follicles which reach the antral stage at oestrus, and are known to be recruited by the periovulatory FSH peak, acquire the potency to produce biologically active inhibin. This is the cohort of follicles from which selection of ovulatory follicles will normally take place. In contrast to inhibin, follicular oestradiol-17 beta concentrations were negligible until the last days of the cycle when oestradiol-17 beta was present in follicles larger than class 2; levels increased with increasing follicle size and a maximal level was found in preovulatory follicles at pro-oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.

Amino Acid Sequence↗
PubMed1994

The gene for familial dystonia with myoclonic jerks responsive to alcohol is not located on the distal end of 9q.

A gene (DYT1) for susceptibility to early-onset torsion dystonia in Ashkenazi Jewish and Gentile kindreds is situated on chromosome 9q32-q34 in a 6-7 cM span between markers AK1 and ASS. To determine whether transmission of familial dystonia with myoclonic jerks responsive to alcohol was consistent with a gene in this region, we studied the 37 members of a Swedish family, of whom 20 were so affected. A lod score of < -2.00 from a two-point linkage analysis with six DNA markers covering a 30 cM span from D9S26 to D9S10 that included the region of the DYT gene indicated that this gene is not located in this region, and that two or more autosomal loci are responsible for hereditary dystonia in humans.

Alcohols↗
PubMed1994

Effects of naloxone infusions on pulsatile thyrotropin secretion.

Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 vs. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 vs. 9.17 +/- 1.36 mU/L). Serum T3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge.

Adult↗
PubMed1994

Testicular and serum levels of inhibin and expression of inhibin subunit mRNAs are differentially affected by hemicastration in rats of various ages.

Age-related short-term effects of hemicastration on testicular weight, serum FSH, immunoreactive inhibin, LH and testosterone, testicular levels of inhibin subunit mRNA expression, and bioactive and immunoreactive inhibin were studied in rats of 8, 15 and 22 days of age. Hemicastration led to an increased weight of the remaining testis after 24 h in 8- and 15-day-old rats, but not in 22-day-old rats. Serum FSH levels were elevated in all hemicastrated rats after 8 h. However, serum immunoreactive inhibin levels were decreased only after 72 h in 8-day-old rats and after 24 h in 15- and 22-day-old rats. Inhibin alpha-subunit mRNA expression was increased in the testes of hemicastrated rats of 8 and 15 days of age, whereas inhibin beta B-subunit mRNA expression was elevated in the testes of 15-day-old rats but not in those of 8- and 22-day-old rats. The increase in alpha-subunit mRNA content per testis was caused by an increased concentration and increased testicular weight, whereas the increase in beta B-subunit mRNA in the remaining testis parallelled the increased testicular weight, indicating that different mechanisms play a role in the regulation of these mRNAs. In 22-day-old rats, a transiently decreased expression of inhibin beta B-subunit mRNA was observed 8 h after hemicastration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

A gene for episodic ataxia/myokymia maps to chromosome 12p13.

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.

Chromosome Mapping↗
PubMed1993

A microsatellite-based index map of human chromosome 11.

We have constructed a continuous index map of 25 microsatellite markers on human chromosome 11. The markers have been typed in 40 CEPH families, have heterozygosities of 69% or higher and can be typed by PCR. The odds against inversion of adjacent marker loci order are at least 10(5):1. The sex average map covers a total of 162 cM with no gap exceeding 15 cM. Total lengths for female and male maps are 205 and 123 cM, respectively. By use of a hybrid cell panel or by in situ hybridization, 16 of the markers have also been mapped cytogenetically, providing a good correlation of the index map with the cytogenetic map. The map will facilitate high resolution mapping of additional polymorphic loci and of disease genes on chromosome 11.

Chromosome Mapping↗
PubMed1992

Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome.

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0-36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 +/- 3.1 to 1.3 +/- 0.2 g/24 h (mean +/- SEM, P less than 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 +/- 1.5 to 1.8 +/- 0.3 g/24 h (P less than 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the 'shunt' pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.

Adult↗
PubMed1992

Prepubertal reduction of the ovarian follicle population by combined LH-releasing hormone antagonist treatment and unilateral ovariectomy influences follicle characteristics but not the ovulation rate at first oestrus.

The effect on first ovulation of the massive reduction of the total pool of ovarian follicles during the infantile and late juvenile period was studied in rats. Treatment with an LH-releasing hormone antagonist (LHRH-A) during infancy (5 mg/kg body weight on days 6, 9, 12 and 15 of life) was combined with unilateral ovariectomy performed on either day 15 (early ULO) or 2-5 days before the expected day of first ovulation (late ULO). Rats were killed on the day of first or second oestrus, when blood was collected and the (remaining) ovaries were prepared for differential counting of follicles and corpora lutea. In addition, blood was sampled 8 h after ULO and the ovaries studied histologically in the group of rats which were unilaterally ovariectomized 2-5 days before first ovulation. The time of first ovulation was not influenced by treatment with LHRH-A, early or late ULO, or a combination of LHRH-A treatment and ULO. Ovulation rate after LHRH-A treatment was decreased, but was still within the normal range in intact rats and in early ULO rats compared with saline-treated controls. Serum FSH concentrations 8 h after ULO performed 2-5 days before first ovulation were similar in saline- and LHRH-A-treated rats (845 +/- 59 and 801 +/- 99 (S.E.M.) micrograms/l respectively) and had increased compared with intact controls (216 +/- 15 micrograms/l). Treatment with LHRH-A resulted in a reduction of more than 50% in healthy and atretic follicles, and late ULO reduced the number of healthy follicles even further.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Outcomes assessment and program evaluation: partners in intervention planning for the educational environment.

Accountability of educational institutions is a current trend in academia. Outcomes assessment provides a method of evaluating educational programs to ensure they are meeting their objectives. This paper presents an overview of outcomes assessment and describes its relationship to and integration with program evaluation. It also describes the implementation of an outcomes assessment program at Kean College of New Jersey, Union, New Jersey. A model for assessment within occupational therapy programs, which parallels a model for intervention planning, is introduced and discussed.

Curriculum↗
PubMed1992

High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus.

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. We have extended our previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analyses gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human/rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosities of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that cosegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXS732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively.

Base Sequence↗
PubMed1991

Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia.

The hereditary dystonias include a clinically heterogeneous group of movement disorders varying in symptoms, age of onset, and drug responsiveness. Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, has been implicated in dystonia because of increased serum levels of DBH in some patients, the influence of catecholaminergic drugs on the human phenotypes, and altered norepinephrine levels in several brain regions in dystonia patients and in genetically dystonic rodents. In addition, markers linked to the dystonia gene in two ethnic groups map close to the DBH locus on human chromosome 9q34. Here we evaluate the inheritance of restriction fragment length polymorphisms near the DBH gene in families with four subtypes of hereditary dystonia: Jewish and non-Jewish, early onset, generalized idiopathic torsion dystonia (ITD); dopa-responsive dystonia; and myoclonic dystonia. In all families, obligate recombination events were observed between the DBH and dystonia genes, thus excluding the DBH gene as the primary defect.

Adolescent↗
PubMed1991

A model for perceived spatial frequency and spatial frequency discrimination.

The responses of labelled spatial frequency channels are combined to generate an index of perceived spatial frequency. Spatial frequency discrimination thresholds are shown to be inversely related to the slope of the function of the index vs spatial frequency, when it is plotted on log-log co-ordinates.

Discrimination, Psychological↗
PubMed1991

Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.

Biodistribution of monoclonal antibody T43 and its F(ab')2 111In-DTPA conjugates were determined in nu/nu mice bearing human breast tumor and rat pituitary tumor xenografts. T43 localized in the target tumor with tumor/blood ratios of 3.9 (P less than 0.01) and 4.5 (P less than 0.05) at 48 and 72 h, respectively. T43 F(ab')2 fragments localized with tumor/blood ratio of 14.2 (P less than 0.1) at 72 h. Tumors as small as 4 mm were detected without computer subtraction technique. These studies suggest that T43 and T43 F(ab')2 might be useful reagents in radioimaging.

Animals↗
PubMed1991

Initial ovulation rate and follicle population after injection of inhibin-neutralizing antiserum in the late-prepubertal rat.

In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days -3/-2) before the expected day of first ovulation, day 38.5 +/- 0.2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Ovulation rate, follicle population and FSH levels in cyclic rats after administration of an inhibin-neutralizing antiserum.

Ovulation rate, follicle growth, serum FSH and oestradiol concentrations were studied after a single intraperitoneal injection of inhibin antiserum in 5-day-cyclic rats. Control rats received (non-immune) serum from castrated sheep or saline. Rats were injected at 10.00 h on dioestrus-1 (D1), i.e. the day following the day of oestrus, or at 17.00 h on dioestrus-2 (D2). The ovaries were excised at necropsy 48 h after injection, or at first or second oestrus after injection. After routine histology fresh corpora lutea were counted and/or differential follicle counts were made. Results from rats injected with either (non-immune) serum from castrated sheep or with saline were not different and were therefore combined to form the control group. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by approximately 39% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. Rats were injected on D1 and killed at first oestrus. The number of fresh corpora lutea was significantly higher in antiserum-treated rats than in controls (13.9 +/- 0.4 vs 11.8 +/- 0.4; P less than 0.05). Other rats injected on D1 were killed either 48 h or at the second oestrus after injection. Blood was collected 8, 16, 24 and 48 h and at first and second oestrus after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The N-methyl-D-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat.

The physiological role of activated hypothalamic N-methyl-D-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0.1-0.2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0.2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0.2, or one injection of 0.5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 x 0.2 mg/kg) or complete (2 x 0.2 and 1 x 0.5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats and ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗