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Biomedical subjects

C Moser

Publications and source records attributed to C Moser.

At least 91 records · Page 5Linked to original sources
PubMed1994

An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.

X-linked adrenal hypoplasia congenita is a developmental disorder of the human adrenal gland that results in profound hormonal deficiencies and is lethal if untreated. We have isolated the gene responsible for the disease, DAX-1, which is deleted or mutated in X-linked adrenal hypoplasia patients. DAX-1 encodes a new member of the nuclear hormone receptor superfamily displaying a novel DNA-binding domain. The DAX-1 product acts as a dominant negative regulator of transcription mediated by the retinoic acid receptor.

Adrenal Insufficiency↗
PubMed1994

Internal Ca2+ ions inactivate and modify ATP-sensitive potassium channels in adult mouse skeletal muscle.

The effects of internal Ca2+ ions on single ATP-sensitive potassium channels (KATP channels) were studied in inside-out membrane patches excised from mouse skeletal muscle. Channel activity was high when patches were excised in a Ca(2+)-free, Na(+)-rich solution and declined irreversibly within seconds in the presence of internal Ca2+ (0.1 and 2 mM). After Ca(2+)-dependent inactivation of the channels, the ATP concentration-response curve was steeper and 50% channel blockage occurred at a lower ATP concentration than before inactivation. ATP (50 microM) in a K(+)-rich solution bathing the intracellular membrane surface reduced the open-probability of KATP channels to 18% before and to 10% after exposure of the patch to internal Ca2+ (0.1 mM). The block of KATP channels by ATP (50 microM) was also enhanced by internal Ca2+ at a concentration of 13 microM. It is concluded that internal Ca2+ ions can both inactivate KATP channels and modify the active channels. KATP channels modified by Ca2+ are blocked more strongly by ATP than unmodified channels.

Adenosine Triphosphate↗
PubMed1994

Pore-formation by Escherichia coli hemolysin (HlyA) and other members of the RTX toxins family.

Escherichia coli hemolysin (HlyA) is a major cause of E. coli virulence. It lyses erythrocytes by a colloid osmotic shock due to the formation of hydrophilic pores in the cell wall. The size of these channels can be estimated using osmotic protectant of increasing dimensions. To show that the formation of pores does not depend critically on the osmotic swelling we prepared resealed human erythrocyte ghosts loaded with a fluorescent marker. When attacked by HlyA the internal marker was released, indicating the formation of toxin channels so large as to let it through. The channels can be directly demonstrated also in purely lipidic model systems such as planar membranes and unilamellar vesicles, which lack any putative protein receptor. HlyA has been recognised as a member of a large family of exotoxins elaborated by Gram-negative organisms including Proteus, Bordetella, Morganella, Pasteurella and Actinobacillus. These toxins have quite different target cell specificity and in many cases are leukocidal. When tried on planar membranes however, even specific leukotoxins open channels not dissimilar from those formed by HlyA, suggesting this might be a common step in their action. Comparison of the hydrophobic properties of six members of the toxin family indicates the presence of a conserved cluster of ten contiguous amphipathic helixes, located in the N-terminal half of the molecule, which might be involved in channel formation.

Bacterial Proteins↗
PubMed1994

The prevalence and some attributes of females in the sadomasochistic subculture: a second report.

Nonprostitute women in the sadomasochism (S/M) subculture have been believed to be rare. A sample of 45 women from the S/M subculture of whom 34 were determined to be nonprostitutes was obtained. This sample is compared with a similar sample obtained by Breslow et al. (1985). Despite methodological differences between the present investigation and that of Breslow et al., interstudy similarities permit conclusions about women in the S/M subculture in addition to the fact that they occur with sufficient frequency to study. The women become aware of their orientation as young adults and most are satisfied with it. They tend to be better educated and less often married than the general population. A majority designate themselves as heterosexual but a substantial minority are bisexual. They tend more often to prefer the submissive role but preference for the dominant role or no preference are found with considerable frequency. Oral sex and bondage are favored activities.

Adult↗
PubMed1993

X-ray crystal structure of ferric Aplysia limacina myoglobin in different liganded states.

The X-ray crystal structure of the ligand-free ferric form of Aplysia limacina myoglobin (pH 6.0) has been refined at 1.7 A resolution (R = 15.1%), and its cyanide, thiocyanate and imidazole derivatives studied by difference Fourier techniques at atomic resolution. The crystallographic R-factors of the three different derivatives reported are 16.1%, 16.1% and 15.6% at 1.8 A, 2.0 A and 2.0 A resolution, respectively. The present results have been analyzed in parallel with previous crystallographic studies on the molecular structures of the fluoride and azide derivatives of ferric Aplysia limacina myoglobin. Ligand binding to the distal site of the heme pocket results in different networks of hydrogen bonds involving to various degrees the bound ligand, residue Arg(66)E10, the heme propionate III, ordered water molecules and/or protein backbone atoms from the CD region. In particular, Arg(66)E10 stabilizes the bound ligand and compensates for the absence of the hydrogen bond donor residue HisE7, commonly present in oxygen-carrying globins.

Animals↗
PubMed1992

[Intra-arterial calcium provocation for the preoperative diagnosis of the location of an occult insulinoma].

Blood-sugar levels below 40 mg/dl were measured during syncope in two female patients (aged 59 and 73 years). Suspected organic hyperinsulinism was confirmed by a fasting test. Ultrasound examination and computed tomography failed to demonstrate an insulinoma. Coeliacomesentericography was then undertaken together with a selective intra-arterial calcium provocation test of the pancreas (0.4 or 0.5 mmol calcium in physiological saline was injected into the pancreas-supplying arteries--proximal and distal splenic, superior mesenteric and gastroduodenal). The insulin level was determined in simultaneously obtained hepatic venous blood. In case 1, the insulin level rose tenfold after calcium injection into the proximal splenic artery, indicating a process in the body of the pancreas. In case 2, a steep rise in insulin occurred after injection into the truncus coeliacus and the proximal and distal splenic artery, suggesting an insulinoma in the tail of the pancreas. The site of the insulinoma was confirmed in both cases at surgery. The adenoma was enucleated in case 1, removed by partial resection of the tail of the pancreas in case 2.--These observations show that occult insulinomas can be localized preoperatively by intraarterial calcium injection with measurement of insulin concentration in simultaneously obtained hepatic venous blood.

Aged↗
PubMed1992

IGF-I and IGF-II expression in human breast cancer xenografts: relationship to hormone independence.

Although the growth of some estrogen receptor (ER) positive breast cancers can initially be hormonally manipulated, all will eventually escape hormonal control. It is possible that the expression of polypeptide growth factors is initially under the control of steroid hormones, while the hormone unresponsive state is characterized by constitutive expression of growth factors. We studied the relationship between hormone responsiveness and IGF expression in xenograft models. The ER+ T61 xenograft was established from a primary breast cancer and has been continually passaged in athymic mice. ER+ MCF-7 cells and ER-MDA-MB-231 cells were grown in tissue culture and then inoculated into athymic mice. ER+ xenograft growth was regulated by estrogen, but with opposite results--T61 xenografts are inhibited by estrogen, while MCF-7 xenografts require estrogen for tumor formation. All xenografts expressed type I and II IGF receptors. Although T61 xenografts also express an alternatively spliced IGF-I mRNA, its expression was not regulated by estrogen. Both xenografts expressed IGF-II in a hormonally regulated manner--T61 levels were depressed by estrogen, while MCF-7 levels were increased. Thus, in these model systems, xenograft regulation of tumor growth is accompanied by parallel changes in IGF-II expression. In the estrogen independent MDA-MB-231 cells, IGF-II was constitutively expressed. These data show that IGF-II expression correlates with estrogen treatment, suggesting that autocrine expression of IGF-II may mediate estrogen-regulated cell growth.

Animals↗
PubMed1992

Lust, lack of desire, and paraphilias: some thoughts and possible connections.

How one develops specific sexual interests (desires, eroticisms, orientation, lust, preferences, etc.) is a basic and essentially unanswered question in sexology. The present paper explores a theoretical relationship between the the development of specific sexual interests and those individuals complaining of lack of desire. The ability of traditional sex therapy to intercede successfully in these problems is discussed.

Cues↗
PubMed1992

[Breast cancer and polypeptide growth factors].

Growth factors are crucially involved in the growth of breast cancer cells and in disease progression, both as mediators of endocrine therapy, as co-factors in the development of hormonal resistance, and as regulators of the extracellular proteolysis that precedes invasion and metastasis. Better characterisation and understanding of the mechanisms of action of the various growth factors might open up new possibilities in therapeutic intervention. Thus it would be possible to include in future research the development of synthetic agonists to the inhibitory growth factors, inhibitors of the stimulatory growth factors, and the development of receptor antagonists to block the binding of stimulatory growth factors to their receptors.

Breast Neoplasms↗
PubMed1991

[Cardiac metastasis as cause of therapy-resistant heart failure].

Ultrasonography revealed a renal tumour (4 x 4 cm) in a 67-year-old man with right-sided lumbar pain and macrohematuria. In addition he had marked nocturnal dyspnoea with dry cough. He had lost about 10 kg in weight. On admission he had atrial fibrillation with an irregular ventricular rate (140 beats/min) and engorgement of the neck veins. Two-dimensional echocardiography, undertaken because of signs of increasing heart failure and a fall of systolic blood pressure to below 100 mm Hg, demonstrated a space-occupying lesion in the right ventricle, 4 x 2 x 1 cm, indicating an intracardiac thrombus or solid tumour. The heart failure continued to worsen, despite treatment with cardiac glycosides, verapamil and diuretics. Hence an exploratory thoracotomy was performed. This revealed an intracardiac tumour which had markedly displaced the right ventricular inflow tract and infiltrated the entire myocardium, but not the tricuspid valve. As much of the tumour as possible was resected, but the patient died postoperatively of heart failure. The intracardiac tumour proved to be a metastasis from the papillary carcinoma of the kidney. This had infiltrated the renal capsule and pelvis and invaded the branches of the right renal vein.

Aged↗
PubMed1991

Total skin electron beam and total nodal irradiation of cutaneous T-cell lymphoma.

Nineteen patients with cutaneous T-cell lymphoma (CTCL) limited to the skin and/or lymph nodes were treated at Hahnemann University with a combination of total skin electron beam and total nodal irradiation (TSEB + TNI). The patients were classified as Stage Ib (1 patient), Stage IIa (8 patients), Stage IIb (5 patients), and Stage IVa (5 patients). Treatment resulted in a complete response in 100% (14/14) of patients with Stage Ib, IIa, and IIb disease, and a CR in 60% (3/5) of patients with Stage IVa disease. The Stage Ib and IIa patients had an overall survival of 100% and a disease-free survival of 44% at 6 years. Four of the five patients with Stage IIb CTCL relapsed within 3 months after completing TSEB + TNI with an overall survival in the group of 40% at 5 years. The Stage IVa patients all relapsed within 7 months and died of their disease within 50 months of completing treatment. The acute effects of TSEB + TNI were well tolerated, but three patients developed second malignancy (lung, kidney and skin) and one patient developed myelodysplasia, possibly the result of radiotherapy.

Female↗
PubMed1990

The radiation therapy of early stage cutaneous T-cell lymphoma.

Results of different radiotherapy schedules used for early stage (T1-2, N0-1, M0) cutaneous T-cell lymphoma (CTCL) are compared in a series of 45 patients (22 patients treated with high dose total skin electron beam therapy (TSEB) with curative intent, 18 patients treated with palliative radiotherapy, and 5 patients treated with high dose local electron beam). At 3, 5, and 10 years after diagnosis the high dose TSEB treatment group had a probability of overall survival of 91%, 86%, and 75%, respectively, compared with 94%, 88%, and 88% for the palliative treatment group. The complete response (CR) rate for the high dose TSEB treatment group was 82% (18/22), compared with a 57% (4/7) complete response rate for seven patients in the palliative group who received low dose TSEB (less than 25 Gy in 6-7 weeks) followed by daily application of topical mechlorethamine hydrochloride (HN2). However, the probability of continued remission at 3, 5, and 10 years was 44%, 44%, and 33%, respectively, for the high dose TSEB group and 25%, 25%, and 0%, respectively, for the low dose TSEB + HN2 group. The median disease-free survival was 17.5 months for the high dose TSEB group versus 5.5 months for the low dose TSEB + HN2 group. The five patients who were treated with high doses of local electrons to a single local field had an overall survival rate of 80%, a median survival rate of 64 months, and a median length of continued remission of 31 months. These results indicate that high-dose electron beam can result in long-term disease-free survival in patients with localized and limited extent skin involvement with cutaneous T-cell lymphoma.

Adult↗
PubMed1990

Iodide-induced hypothyroidism in patients after thyroid resection.

The purpose of this investigation was to determine whether an intrinsic defect in thyroid hormone production is required for the development of iodide-induced hypothyroidism or does it also develop in TSH-stimulated normal thyroid tissue. To answer this question, we studied the response to iodine administration (180 mg iodide daily for 3-4 months) in eight euthyroid patients who had had partial thyroidectomies 2 months to 10 years previously for benign thyroid nodules, and in three euthyroid control subjects. In all 11 euthyroid patients, basal serum TSH concentrations increased during iodide administration. In six of the eight patients who had previous thyroid operations and in two of the three control patients, basal serum TSH concentrations increased into the abnormal range (greater than 6 U ml-1). Increased serum TSH concentrations were noted as early as 1 week after potassium iodide had been started and the increased levels persisted during the period of iodide administration. Although basal values for serum TSH concentration were initially within the normal range, those patients with highest basal serum TSH values developed the greatest increase in TSH in response to potassium iodine. Among the eight patients treated by partial thyroidectomy, serum T4 concentrations decreased in five, serum T3 concentration decreased in three and all five developed mild symptoms of hypothyroidism while receiving iodide. Serum T4 concentrations also decreased slightly in two of the three control patients. Serum total iodine levels increased from 7.0 +/- 0.5 to 315.7 +/- 108.6 g dl-1 (mean-+/- standard error) during potassium iodide administration, but there was no correlation between the level of serum iodide concentration achieved and inhibition of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Fluperlapine vs haloperidol: a comparison of their neuroendocrinological profiles and the influence on serum lipids.

Twelve male patients suffering from acute paranoid schizophrenia, randomly receiving fluperlapine - a new dibenzodiazepine very similar to clozapine - or haloperidol were included in a double blind study. Plasma levels of triglyceride, cholesterol and HDL-cholesterol, prolactin, thyroxine, triiodothyronine, ACTH and cortisol were determined. There was no evidence, that fluperlapine has any relevant influence on those hypothalamic-pituitary axis mediated hormones with the possible exception of plasma lipids. These findings, together with the clinical experiences, suggest that fluperlapine might have a different mode of action than conventional neuroleptics.

Adrenocorticotropic Hormone↗