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Biomedical subjects

K Weismann

Publications and source records attributed to K Weismann.

At least 19 recordsLinked to original sources

Role of altered G-protein expression in the regulation of myocardial adenylate cyclase activity and force of contraction in spontaneous hypertensive cardiomyopathy in rats.

OBJECTIVE: The question of this study was whether alterations in the inhibitory guanine-nucleotide binding protein alpha-subunits (G(i)alpha) contribute to alterations in adenylate cyclase regulation in hypertensive cardiomyopathy of spontaneously hypertensive rats (SHR). DESIGN AND METHODS: G(i)alpha was measured by pertussis toxin-catalysed 32P-adenosine 5'-pyrophosphate (ADP)-ribosylation and radioimmunochemically by competition of rat myocardial membrane extracts to DS 4 antiserum binding to the 125I-radiolabelled C terminus of retinal transducin alpha (125I-KENLKDCGLF). Cardiac beta-adrenoceptors, m-cholinoceptors as well as isoprenaline-, guanine-nucleotide [Gpp(NH)p]- and forskolin-stimulated adenylate cyclase activity and inotropic responses to isoprenaline and carbachol were studied in SHR and age-matched Wistar-Kyoto (WKY, control) rats. RESULTS: In native membranes of SHR there was an increase in pertussis toxin substrates, but a larger increase in the presence of non-ionic detergent Lubrol PX. The radioimmunological quantification of G(i)alpha revealed an increase in membrane extracts of SHR. In addition, myocardial beta-adrenoceptors and myocardial m-cholinoceptors were reduced in SHR compared with in WKY rats. Basal adenylate cyclase, isoprenaline-, Gpp(NH)p- and forskolin-stimulated adenylate cyclase activities were also reduced. However, in the presence of 5 mmol/l MnCl2 no differences in adenylate cyclase activities between SHR and WKY rats were detected under either condition. CONCLUSIONS: The present study shows that the amount of G(i)alpha-proteins and not only pertussis toxin substrates are increased in membranes of hypertrophic hearts from SHR without heart failure. The results obtained with pertussis-labelling depended strongly on the substrate quality of G(i)alpha. Increased G(i)alpha expression and reduced beta-adrenoceptor number might have functional relevance in the regulation of adenylate cyclase activity and force of contraction in SHR. An increase in G(i)alpha expression might play a pathophysiological role, not only in terminal heart failure, but also in hypertrophic cardiomyopathy.

Adenylate Cyclase Toxin

Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.

Adenylyl Cyclases

Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases.

The retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs.

Drug Interactions

The relation between lichen planus and hepatitis C: a case report.

A case of simultaneous occurrence of lichen planus (LP) and hepatitis C in the same patient is presented. The patient had received treatment with interferon alpha for her chronic liver disease, and the association between LP, hepatitis C and interferon alpha treatment is discussed.

Female

[Zinc deficiency in a premature infant].

A premature infant with a birth-weight of 1,218 g developed severe zinc depletion about two months after birth. He had received his mother's breast-milk which was found to have a low zinc content of about 5 mumol/l. The clinical symptoms of zinc deficiency included stunted growth, catarrhal symptoms and a characteristic eczematous eruption on the face and diaper region known as acrodermatitis. Serum zinc was lowered (6.8 mumol/l) and so was serum alkaline phosphatase activity. Oral zinc sulphate supplementation, initially 22.5 mg daily and subsequently 11 mg zinc daily, had a prompt effect on the patient's well-being and the skin was restored to normal after about a week.

Humans

[Human papillomavirus (HPV) vulvitis].

Human papilloma virus vulvitis with flat elements resembling leucoplakia may be diagnosed by application of a 5% acetic acid solution and subsequent biopsy and histological examination. The condition causes irritation with dyspareumia and is so frequent that the diagnosis and initial treatment may be undertaken by the general practitioner.

Adult

Histopathology of acute human immunodeficiency virus exanthema.

Acute exanthema occurs in patients who are human immunodeficiency virus (HIV) positive before they become seropositive. The patients have influenza like symptoms and a macular skin rash on the upper trunk. Histopathological investigation of skin punch biopsy specimens from four patients with acute HIV exanthema showed a normal epidermis and a sparse dermal, mainly perivascular, lymphocytic/histiocytic infiltrate around vessels of the superficial plexus. Histopathological changes of the exanthema of acute HIV infection are non-specific and resemble those of other acute viral exanthema, but when both the histopathological features and the clinical picture are suggestive, the clinician should take into consideration the possibility of HIV infection.

Acquired Immunodeficiency Syndrome

The Yemenite deaf-blind hypopigmentation syndrome. A new oculo-dermato-auditory syndrome.

We have seen a Yemenite sister and brother with cutaneous hypomelanotic and pigmented spots and patches, microcornea, coloboma, severe hearing loss and normal karyotypes. Histopathological examinations of the skin showed absent melanocytes in the depigmented areas; in the normal and hyperpigmented skin there was abundant melanotic pigment. Similar patients have not been described previously, but there are corresponding mutations in mice and rats.

Abnormalities, Multiple

Zinc gluconate lozenges for common cold. A double-blind clinical trial.

In a double-blind clinical trial, a total of 463 volunteers were enrolled in a study designed to compare the effects of zinc gluconate lozenges (4.5 mg zinc) and a placebo for common cold. The tablets were to be taken every 1-1 1/2 waking hours at the first symptoms and for the following days until the common cold was over, but for no longer than 10 days. During the winter months of 1987 and 1988, 145 experienced a common cold and 130 completed the study. For final analysis, 61 patients in the zinc lozenge group and 69 patients in the placebo lozenge group were evaluated. Based on the patients' records the duration and severity of the common cold were compared. No statistically significant differences were found between the patient groups. Two recent studies using a five-time higher zinc dose per lozenge for common cold showed a significant, positive effect, but associated with frequent side-effects, first of all taste distortion. In the present study there was a weak tendency (not statistically significant, p = 0.12) towards more patients in the zinc lozenge group than in the placebo lozenge group reporting side-effects.

Adolescent

[Good must drive out evil. On cosmetic treatment agents and earlier times' viewpoint on skin diseases].

The interest in skin preparation and "cosmetics" has increased in recent years. This development, which seeks to satisfy the patients' wishes and requirements for a kind but at the same time effective treatment is of historical significance. The treatment of skin diseases was in earlier times pervaded by another attitude, to the effect that evil should drive out evil, e.g. syphilis, scabies and psoriasis. The physician prescribes but it is the patient who executes the treatment, a point more often borne in mind with regard to the diseases of today.

Cosmetics

Prolonged application of acetic acid for detection of flat vulval warts.

Macroscopic visualization of flat vulval warts is usually obtained by application of 3-5% acetic acid for 2-5 min. However, we have recently seen two women with symptoms suggesting the presence of condylomatous vulvitis where the use of 5% acetic acid for 10-15 min. was necessary for aceto-white lesions to develop. In both women, histologic examination indicated the presence of a Human papillomavirus infection. Prolonged application of acetic acid 5% should be considered among women in whom vulval papillomavirus infection is suspected.

Acetates

[Petroleum burns--toxic contact dermatitis].

A great proportion of older housing facilities in Copenhagen are occupied by elderly individuals whose flats are heated by petroleum stoves. These individuals have frequently reduced mobility and may risk falling while filling their stoves. They may thus be exposed to the effect of the toxic fluid on the skin. The clinical pictures in two cases are described.

Aged