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Biomedical subjects

P Kramer

Publications and source records attributed to P Kramer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Significance of oestradiol for follicular development in hypogonadotrophic immature rats treated with FSH and hCG.

Administration of hCG (0.5 i.u.) to immature female rats that were made hypogonadotrophic by injections of an LHRH-antagonist at 22, 24, 26 and 28 days of age and in which follicular development was induced by FSH (10 i.u., given from day 26 until day 29) stimulates follicles to grow to their preovulatory size with a low amount of atresia. To investigate whether this effect of hCG on follicular growth is due to stimulation of oestradiol production, intraovarian concentrations of oestradiol were suppressed by an aromatase inhibitor and oestradiol action was blocked by an oestrogen antagonist; both of these were administered from day 25 until day 29. By day 30 this treatment had resulted in an increase in the percentage of atretic follicles. In turn, oestradiol benzoate (100 micrograms or 1000 micrograms day-1), given from day 26 until day 29 in rats treated with 10 i.u. FSH, resulted in (1) an increase in the total number of antral follicles, (2) an increase in follicular size and (3) a decrease in the percentage of atretic follicles. Although the administration of 1000 micrograms oestradiol benzoate can mimic the effects of 0.5 i.u. hCG on follicular growth to a large extent, the number of follicles with a diameter > 575 microns in rats treated with FSH plus oestrogen was smaller than that in rats treated with FSH plus hCG (10 +/- 2 and 24 +/- 2, respectively). Furthermore, a single injection of 10 i.u. hCG given on day 29 was used to induce ovulation: fewer ova were found in rats treated with FSH plus 1000 micrograms oestrogen than in rats treated with FSH plus hCG (15.2 +/- 2.1 and 46.5 +/- 1.6, respectively). From these studies, it is concluded that the effects of hCG on follicular growth and atresia can be largely attributed to the mitotic and anti-atretic effect of oestradiol. However, part of the effect of hCG cannot be explained on the basis of oestradiol action.

Animals↗
PubMed1997

Perceptual grouping in space and time: evidence from the Ternus display.

We report three experiments investigating the effect of perceptual grouping on the appearance of a bistable apparent-motion (Ternus) display. Subjects viewed a Ternus display embedded in an array of context elements that could potentially group with the Ternus elements. In contrast to several previous findings, we found that grouping influenced apparent motion perception. In Experiment 1, apparent motion perception was significantly affected via grouping by shape similarity, even when the visible persistence of the elements was controlled. In Experiment 2, elements perceived as moving without context were perceived as stationary without context were perceived as moving when grouped with moving elements perceived as stationary without context were perceived as moving when grouped with moving context elements. We argue that grouping in the spatial and temporal domains interact to yield perceptual experience of apparent-motion displays.

Adult↗
PubMed1996

A second gene for cerulean cataracts maps to the beta crystallin region on chromosome 22.

Congenital cataracts are one of the most common major eye abnormalities and often lead to blindness in infants. At least a third of all cases are familial. Within this group, highly penetrant, autosomal dominant forms of congenital cataracts (ADCC) are most common. ADCC is a genetically heterogeneous group of disorders, in which at least eight different loci have been identified for nine clinically distinct forms. Among these, Armitage et al. (Nature Genet. 9: 37-40, 1995) mapped a gene for cerulean blue cataracts to chromosome 17q24. Bodker et al. (Am. J. Med. Genet. 37: 54-59, 1990) described a large family with cerulean blue cataracts, in which the affected daughter of affected first cousins was presumed to be homozygous for the purported gene. We report linkage in this family to the region on chromosome 22q that includes two beta crystallin genes (CRYBB2, CRYBB3) and one pseudogene (CRYBB2P1). The affected female in question is homozygous at all markers.

Cataract↗
PubMed1996

Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13.

Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.

Chromosome Mapping↗
PubMed1996

Effects of metoclopramide on fasting-induced TSH suppression.

Short-term caloric deprivation leads to suppression of TSH secretion in healthy subjects, but the mechanism of this effect is unknown. Since dopamine inhibits TSH secretion at physiologic levels, increased endogenous dopamine activity may cause the TSH suppression observed during fasting. To test this hypothesis, 11 healthy subjects underwent four studies: (1) Baseline-subjects were allowed ad libitum food. (2) MCP-subjects were allowed ad libitum food and received iv metoclopramide (MCP) at 30 micrograms/kg/h over 48 h. (3) Fasting-subjects received no caloric intake for 56 h. (4) Fasting+MCP-subjects fasted for 56 h, and received iv MCP during the final 48 h of the study. Serum TSH levels were measured every 15 min during the final 24 h of each study, and a TRH stimulation test was performed at the conclusion of each study: 56 h of fasting decreased 24 h mean TSH levels and TSH pulse amplitude by 40%, with blunting of the TSH response to TRH. MCP infusions increased 24 h mean TSH levels and TSH pulse amplitude 26-34%, with no differences between the fasting and nonfasting studies. MCP infusions did not normalize TSH levels, TSH responses to TRH, or serum T3 levels during fasting. These data suggest that endogenous dopaminergic activity does not play a major role in fasting-induced TSH suppression in healthy subjects.

Adolescent↗
PubMed1996

Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men--a clinical research center study.

In healthy subjects, short term fasting suppresses the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum levels of TSH and LH. However, effects of fasting on pulsatile release of TSH, LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each underwent two 2-day studies: a baseline study during normal caloric intake and a fasting study during 56 h of caloric deprivation. During the final 24 h of each study, blood samples were drawn every 15 min for measurement of serum TSH, LH, FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50% suppression of mean TSH levels and TSH pulse amplitude, without altering TSH pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH levels only decreased by 13%, without changes in FSH pulse parameters, whereas mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show that short term fasting has a greater suppressive effect on the hypothalamic-pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more resistant to fasting-induced suppression than LH, implying discordant regulation of the two gonadotropins during nutritional deprivation. alpha-Subunit suppression during fasting appears to parallel that seen for LH.

Adult↗
PubMed1996

Recombinant FSH-induced follicle development in immature rats treated with an LHRH antagonist:a direct effect of RU486 on follicular atresia.

To investigate whether the progesterone antagonist RU486 has a direct effect on ovarian function, it was administered to immature female rats rendered hypogonadotrophic by administration of an LHRH antagonist and in which follicle development was stimulated by recombinant human FSH (recFSH). In the first experiments the effects of LHRH antagonist and recFSH on follicle growth were evaluated. Female rats of 22 days of age were injected with an LHRH antagonist (Org 30276; 500 micrograms/100 g body weight) every other day. This treatment resulted in a tenfold decrease in serum LH concentrations and a twofold decrease in serum FSH concentrations at day 30 and caused a reduction in the number and size of antral follicles. Treatment with recFSH (Org 32489) twice daily from day 26 for 4 days in a total dose ranging from 5 to 20 IU/animal increased the number and size of antral follicles in a dose-related manner and resulted after 20 IU recFSH in a tenfold increase in the concentration of inhibin in serum and ovaries at day 30. Once it was established that LHRH antagonist treatment in immature rats could be used to study the effects of gonadotrophins or steroids on follicle function, this animal model was used to study the effects of RU486 on the ovary. RU486 was administered (twice daily for 4 days, 1 mg/injection) to LHRH antagonist-treated rats in which follicular growth and differentiation were stimulated by 10 IU recFSH or by 10 IU recFSH plus 0.5 IU human chorionic gonadotrophin (hCG). RU486 had no effect on circulating levels of LH and FSH, but stimulated follicular atresia both in rats treated with recFSH alone and in rats treated with recFSH and hCG. Inhibin concentrations both in serum and ovaries were significantly increased after hCG treatment. RU486, however, did not increase inhibin in the rats treated with recFSH and in those treated with recFSH and hCG. In summary, the present study has demonstrated that (1) immature rats treated with an LHRH antagonist can be used to study the effects of gonadotrophins and steroids on follicular function and (2) RU486 has a direct stimulatory effect on follicular atresia.

Animals↗
PubMed1995

The CEPH consortium linkage map of human chromosome 11.

The CEPH consortium framework map of chromosome 11 is presented. The map was generated from CEPH family DNAs with 181 probe/enzyme combinations contributed by 20 laboratories. Seventy-seven of the loci are defined by microsatellite polymorphisms that can be typed by the PCR. A total of 42 loci have been placed on the map with likelihood support of at least 1000:1. The female, male, and sex-average maps extend for 179.6, 110.8, and 145.3 cM, respectively. The largest interval on the sex-average map is less than 11 cM, and the average distance between uniquely placed loci is 4 cM. The genotypic data obtained for map construction have been used to identify the positions of crossovers on the chromosomes of CEPH family children, allowing the localization of new markers without computationally intensive likelihood models and providing a basis for efficient extension of the linkage map to higher resolution.

Adult↗
PubMed1995

Fever and rigors as sole symptoms of azathioprine hypersensitivity.

The case history of a haemodialysis patient with fever and rigors is presented. This diagnostic problem turned out to be a hypersensitivity reaction to azathioprine, with identical complaints recurring after a rechallenge with azathioprine, findings which resolved on discontinuation of this drug. The more extended indications for use of azathioprine warrant attention to the possibility of side-effects like drug fever.

Azathioprine↗
PubMed1995

Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population.

We have examined data on six closely linked microsatellite loci on chromosome 9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia (ITD). Our data show that the vast majority (> 90%) of early-onset ITD cases in the Ashkenazi population are due to a single founder mutation, which we estimate first appeared approximately 350 years ago. We also show that carriers preferentially originate from the northern part of the historic Jewish Pale of settlement (Lithuania and Byelorussia). The recent origin of this dominant mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest that the Ashkenazi population descends from a limited group of founders, and emphasize the importance of genetic drift in determining disease allele frequencies in this population.

Alleles↗
PubMed1995

Adult onset idiopathic torsion dystonia is excluded from the DYT 1 region (9q34) in a Swedish family.

A gene (DYT1) for early onset idiopathic torsion dystonia was mapped to chromosome 9q34 in non-Jewish and Jewish families. The DYT1 gene region has been excluded in other families with adult onset and cervical or cranial onset idiopathic torsion dystonia from the United States, Great Britain, and France. The role of DYT1 in a Swedish family with adult onset idiopathic torsion dystonia in four generations was examined. The disease seems to be inherited in an autosomal dominant mode with reduced penetrance in this family. There were 10 affected family members, with a mean age of onset of 27 (range 18 to 50) years. The disease showed variable expression, with focal, multifocal, and generalised forms of dystonia in different family members. Genetic analysis excluded the chromosomal region containing the DYT1 locus as being responsible for dystonia in this family.

Adolescent↗
PubMed1995

Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth.

During fetal development, anti-müllerian hormone (AMH) is produced only by Sertoli cells, but postnatally, granulosa cells also produce this peptide growth/differentiation factor. We recently identified a candidate AMH type II receptor (AMHRII). In the present study, postnatal ovarian AMH and AMHRII messenger RNA (mRNA) expression was studied by in situ hybridization and ribonuclease protection. In ovaries from adult rats, AMH and AMHRII mRNAs were found to be mainly expressed in granulosa cells from preantral and small antral follicles. Corpora lutea and large antral follicles express little or no AMH and AMHRII mRNA, and primordial follicles and oocytes appeared to be AMH and AMHRII mRNA negative. Thecal and interstitial cells express no detectable AMH mRNA and little or no AMHRII mRNA. The colocalization of AMH and AMHRII mRNAs in granulosa cells of specific follicle types suggests that actions of AMH via AMHRII are autocrine in nature. There is a decreased level of AMH and AMHRII mRNA expression when follicles become atretic. Both mRNA species are eventually lost from atretic follicles, although AMHRII mRNA expression seems to persist somewhat longer than AMH mRNA. During the estrous cycle, no marked changes in the patterns of AMH and AMHRII mRNA expression were detected, except at estrus, when expression of both mRNA species in preantral follicles was decreased compared to that on the other days of the cycle. On postnatal day 5, total ovarian AMH mRNA expression is low and is located in small preantral follicles. During the first weeks of postnatal development, AMH mRNA expression in preantral follicles increases, and the later formed small antral follicles also express AMH mRNA. In contrast, AMHRII mRNA is expressed on postnatal day 5 at a higher level than AMH mRNA, but cannot be localized to specific cell types. From postnatal day 15 onward, AMHRII mRNA expression becomes more restricted to the preantral and small antral follicles. Treatment of prepubertal rats with GnRH antagonist (Org 30276) and human recombinant FSH (Org 32489) or with GnRH antagonist and estradiol benzoate resulted in follicle growth and inhibition of AMH and AMHRII mRNA expression in some, but not all, preantral and small antral follicles. These results indicate that FSH and estrogens may play a role in the down-regulation of AMH and AMHRII mRNA expression in vivo when small antral follicles differentiate into large antral follicles. Furthermore, the FSH surge on the morning of estrus may inhibit AMH and AMHRII mRNA expression in preantral follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Recombinant FSH (Org32489) induces follicle growth and ovulation in the adult cyclic rat.

The effects of a single injection of recombinant human FSH (rhFSH; Org32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioestrus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ovulation rate on the day of expected oestrus. However, an additional, precocious ovulation resulting in a normal number of corpora lutea (13.3 +/- 0.4, n = 6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vaginal plugs the next morning, was observed at this ovulation. Follicle counts showed a loss of large antral follicles due to ovulation and increased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as well as additional recruitment of new antral follicles. The endogenous serum FSH concentration on the subsequent day of oestrus (65 h after the rhFSH injection) as well as recruitment of small antral follicles were lower in the rhFSH-treated rats than in saline-treated controls. The ovulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group. Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH preparation (i.e. metrodin). Furthermore, the direct induction of ovulation by rhFSH or metrodin could not be prevented by the injection of an LHRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Further studies on the regulation, localization and function of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland.

Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anterior pituitary gland is accounted for by the TRH-like tripeptide pyroglutamyl-glutamyl-prolineamide (pGlu-Glu-ProNH2, < EEP-NH2). The present study was undertaken to investigate further the regulation, localization and possible intrapituitary function of < EEP-NH2. Anterior pituitary levels of < EEP-NH2 were determined between days 5 and 35 of life, during the oestrous cycle and after treatment with the luteinizing hormone-releasing hormone (LHRH) antagonist Org 30276. Treatment of adult males with the LHRH antagonist either for 1 day (500 micrograms/100 g body weight) or for 5 days (50 micrograms/100 g body weight) reduced anterior pituitary < EEP-NH2 levels by 25-30% (P < 0.05 versus saline-treated controls). Anterior pituitary < EEP-NH2 increased between days 5 and 35 of life. In females, these levels were 2- to 3-fold higher (P < 0.05) than in males between days 15 and 25 after birth; these changes corresponded with the higher plasma follicle-stimulating hormone (FSH) levels in the female rats. After day 25, < EEP-NH2 levels in female rats decreased in parallel with a decrease in plasma FSH. Injections with the LHRH antagonist (500 micrograms/100 g body weight), starting on day 22 of life, led to reduced contents of < EEP-NH2 in the anterior pituitary gland of female rats on days 26 and 30 (55 and 35% decrease respectively). Levels of < EEP-NH2 in the anterior pituitary gland did not change significantly during the oestrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗