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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 289 records · Page 16Linked to original sources

Glucocorticoids directly affect spectrophotometry of bilirubin in amniotic fluid.

Dexamethasone or prednisolone, added in vitro to bilirubin-containing amniotic fluid, produces a time-dependent decrease in the 450-nm absorbance of the pigment. Neither the chemical determination of bilirubin in amniotic fluid nor the lecithin/sphingomyelin ratio as determined by thin-layer chromatography is affected by these glucocorticoids. The effect probably is not a result of displacement of bilirubin from its binding sites on albumin, because the absorbance of a solution of crystalline bilirubin at 450 nm is unaffected by added bovine serum albumin. Light scattering of amniotic fluid increases slightly when dexamethasone is added, whether or not low concentrations of bilirubin (less than 1.6 mumol/L) are present. Thus the effect on absorbance evidently is not ascribable to supersaturation and formation of a colloidal sol of bilirubin particles. This direct interference of glucocorticoids with the spectrophotometry of bilirubin in amniotic fluid prompts cautious interpretation of such data as an index to the severity of hemolytic disease of the fetus, specifically in cases of Rhesus-isoimmunization that are being treated with glucocorticoids.

Amniotic Fluid↗

Hormone-responsive myofibrillar protease activity in cultured rat myoblasts.

The effect of exposure to dexamethasone and serum-deprivation on myofibrillar protease activity was determined by following cleavage of [14C]globin by isolated myofibrils obtained from rat skeletal muscle in culture. Dexamethasone [10(-7) M] produced a 46% increase in protease activity, and serum-deprivation caused a 50% increase in activity over that of the enzyme in control cultures. The increases in proteolysis occurred concurrently with increased rate of overall protein degradation in these cells and were not associated with changes in cell viability. In cultured rat cardiac muscle cells dexamethasone failed to enhance myofibrillar protease activity, while serum-deprivation produced a 52% increase in the enzyme activity. Addition of insulin (50 mU/ml) to the cultures did not affect proteolysis or myofibrillar protease activity, but completely prevented the dexamethasone-induced increase of these activities. This effect of insulin suggests that the increase of muscle proteolysis in insulin-deficient diabetic animals reflects an enhanced response of the muscle to circulating glucocorticoids rather than a direct effect of insulin-deprivation on muscle proteolysis. Taken together, the present observations indicate that muscle cells in culture retain the ability to respond to catabolic stimuli by adaptive changes in the myofibrillar protease activity in a manner analogous to that of their parent tissue in the intact animal.

Animals↗

A new approach to the management of epidermoid carcinoma of the anal canal.

Until recently most squamous cell carcinomas of the anal canal were treated by radical surgery. Radiation therapy was only considered for palliation in case of inoperable tumors. Important progress has been made in the knowledge of the natural history of the disease and in the field of radiotherapy. Anal canal squamous cell carcinoma should not be treated any longer by the same procedure as adenocarcinoma of the lower rectum, because both these diseases differ markedly. Multimodality therapy with radiotherapy as first approach has been considered. This series of 121 cases treated since 1971 and followed more than three years suggests that three protocols based on irradiation followed or not by surgery should be used according to the extent of the disease. Of the 72 patients with resectable tumor, the five-year survival rate was 65%. Three-quarters of the patients cured had normal anal function. The rate of death from cancer was 18%. The method requires an accurate assessment of the extent of the tumor and of its pelvic lymphatic spread. Great care must be taken in planning treatment in a close cooperation between radiotherapist and surgeon.

Adult↗

[Artificial blood. Experimental studies on fluorocarbons as chemical blood substitutes].

Fluorocarbonates are organic compounds capable of carrying oxygen and surrendering it to tissues by means of biological sound modalities. Experimentation of an emulsion consisting of perfluorotripropylamine and perfluorodecaline (Fluosol DA 20%) as a blood substitute is reported. Acute (Ht less than 1%) and chronic morphological (Ht = 15%) studies were performed on rats, and a semi-acute biochemical and morphological protocol (Ht = 21%) was experimented in pigs. The first signs of altered cerebral electrical activity occurred at Ht = 2% in the acute experiments, and death due to respiratory arrest took pace at Ht = 0.5%. In the semiacute and chronic experiments, widespread infiltration of fluorocarbonic micelles was noted on histological and electron microscope lung and liver preparations.

Acid-Base Equilibrium↗

A cytogenetic study of a population of mentally retarded males with special reference to the marker (X) syndrome.

A cytogenetic survey of a population of 274 mentally retarded males on community placement is described. Thirty-five had an aneuploid chromosome constitution and five had the mar(X) syndrome. The range of clinical variation among the mar(X) probands and their affected relatives is described. Family studies were possible for four of the five mar(X) probands and in two families the mar(X) gene was apparently transmitted through a clinically normal male, suggesting that this type of male transmission may be a not uncommon phenomenon.

Adult↗

In vitro production of corticosteroid binder IB in the presence of proteolytic inhibitors.

The effect of proteolytic inhibitors on the temperature-dependent formation of corticosteroid binder IB in rat kidney cytosol was examined. Antipain increased the apparent binding of [3H]-triamcinolone acetonide in the cytosol. Leupeptin, chymostatin, soya bean trypsin inhibitor and lima bean trypsin inhibitor did not affect total binding, while L-1-tosylamide-2-phenylethyl chloromethyl ketone, N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride markedly reduced the charcoal resistant steroid binding. However, none of the inhibitors added during tissue homogenization, steroid binding or activation affected the extent of heat-dependent conversion of the [3H]-triamcinolone acetonide-receptor complexes to the IB form, which was characterized by its exclusion from DEAE-Sephadex ion exchanger. In contrast, sodium molybdate (10 mM) effectively inhibits IB formation without inhibiting protease activity of rat kidney cytosol. These observations indicate that the temperature-dependent formation of corticosteroid binder IB in vitro does not involve proteolytic transformation of unbound or steroid-bound cytosolic proteins. Addition of antipain (3 mM) to the cytosol markedly increased the radioactivity in the buffer prewash of DEAE-cellulose columns (apparent IB) only when the inhibitor was added prior to charcoal adsorption. However, a similar peak in the prewash also was obtained with receptor-free cytosol. Antipain had no effect on the rate of dissociation of performed [3H]-triamcinolone-acetonide-receptor complexes nor did it increase the amount of receptor adsorbed to hydroxylapatite. Chromatography on Sephadex G-25 and P-2 columns showed that the increased activity in the charcoal-resistant fraction in the presence of antipain is due to unbound steroid. Thus, antipain interferes with the ability of charcoal to remove unbound steroid from the cytosol.

Animals↗

Comparison of corticosteroid binder IB with the alpha-chymotrypsin- and RNase-treated hepatic glucocorticoid receptors.

Rat liver and kidney cytosolic extracts contain the glucocorticoid receptor (binder II) and corticosteroid binder IB, both of which possess the steroid- and DNA-binding domains. Since it has been speculated that the smaller binder IB may be generated from binder II by proteolysis, the chymotrypsin-produced receptor fragment in rat liver cytosol has been compared with binder IB in terms of charge, size and DNA binding characteristics. The [3H]triamcinolone acetonide-receptor complex is converted to a smaller fragment by short term digestion (10 degrees C, 30 min) with 100 micrograms/ml alpha-chymotrypsin. Although the chymotrypsin fragment produced from previously heat-activated binder II and binder IB both exhibit DNA-binding capability, they differ in charge and size. Whereas the alpha-chymotrypsin-treated receptor has a Stokes radius of 30 A and elutes from DEAE-cellulose at 0.06 M potassium phosphate in a linear salt gradient, binder IB has a Stokes radius of 20 A and elutes in the buffer wash of the DEAE-cellulose column. Thus, while binder IB can be resolved from the heat-activated form of the [3H]TA-receptor on DEAE, the heat activated alpha-chymotrypsin product elutes from the anion exchange resin at the same ionic strength as intact activated binder II (i.e. at 0.05 M potassium phosphate), and the unactivated intact receptor elutes at about 0.20 M potassium phosphate. A more extended digestion with alpha-chymotrypsin (24 h, 0 degrees C) results in elimination of the DNA binding site without further reduction of the Stokes radius or change in the elution pattern from DEAE-cellulose. Furthermore, molybdate completely blocks formation of binder IB but does not inhibit the production of the receptor fragment by alpha-chymotrypsin. Treatment of the hepatic [3H]TA-receptor complex with RNase has no effect on the charge, size or DNA binding properties of the bound receptor. These results suggest that RNase does not activate the [3H]TA-receptor complex nor does it produce a IB-like component in the liver cytosol. The present results are consistent with the hypothesis that binder IB is formed in vitro by a process which may not involve proteolytic cleavage or RNase-induced modification of the glucocorticoid receptor (binder II).

Animals↗

Developmental aspects of immunologically characterized proteins.

The spectrum of clinical tests for proteins characterized by their antigenic rather than by their enzymatic properties has been very limited, and still is today. This is mainly due to technical problems in the development of tests for such "antigens". The recently developed hybridoma technology has supplied us with the urgently needed new approach to overcome these problems. It is now possible to develop specific monoclonal antibodies against any determinant on antigens in any tissue, membrane or extract without the need to prepare antigens of high purity. Diagnostically valuable tissue marker molecules without known biological activity have become accessible, and can be detected and quantitated in tissues and body fluids with the new reagents. In most of the tests that will become available now or in the near future, polyclonal antisera will be substituted by monoclonal antibodies. Future developments, however, will exploit the advantages of the new technology to their full extent. In this paper, the advantages and disadvantages of monoclonal antibodies are evaluated and illustrated by the example of monoclonal antibodies to human kidney tissue antigens. Future developments comprising all fields of clinical diagnosis as well as applications in therapy are discussed.

Animals↗

Phorbol ester-induced adhesion of murine erythroleukemia cells: possible involvement of cellular proteases.

Phorbol ester tumor promoters produce a rapid increase in adhesiveness of murine erythroleukemia (MEL) cells. Following treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and other tumor promoters, these cells adhere to the surface of the culture dish or become agglutinated to each other. Structurally related compounds which are devoid of tumor promoting activity failed to induce agglutination of MEL cells. Pentamidine isethionate (PI) and tosylamide-phenylethyl-chloromethyl ketone, two known inhibitors of trypsin-like enzymes, prevent the phorbol esters-induced adherence and agglutination. A short exposure to TPA results in an increase in protease activity at the alkaline pH range. This TPA-induced proteolytic activity is inhibited by PI. Induction of erythroid differentiation by hexamethylene-bisacetamide is associated with a decrease in TPA-induced cell adhesion and TPA-induced proteolytic activity. Taken together, these results suggest the participation of an alkaline proteolytic activity in the membranal changes evoked by phorbol esters.

Animals↗

A study of mental retardation in children in the Island of Hawaii.

Eighty-one probands from an initial population of 223 school-aged retarded individuals were assessed by history, clinical examination and, where appropriate, cytogenetic analysis. In 51 individuals, the retardation occurred as an isolated event within the family, whereas 30 patients had a family history of retardation. In 39 of the isolated individuals, the retardation was either related to environmental factors or associated with a major neurological abnormality. The remaining 12 patients were phenotypically normal with no cytogenetic abnormality. Of the 30 probands from 15 families with a history of retardation, 3 families had X-linked syndromes. One, with 4 proband daughters, had the mar(X) syndrome and two families were considered to have the phenotypically similar syndrome but without demonstrating the mar(X). In an additional 5 families, the distribution and clinical features of the affected individuals were compatible with nonspecific X-linked mental retardation.

Child↗

[Cancer of the rectum: current trends in radiotherapy in conservative treatment].

Conservative treatment of rectal cancer by intracavitary irradiation (Philips contact x-ray therapy followed or not by Iridium implant) is only applicable to tumours which are thought to have no lymphatic spread. A strict selection of cases is compulsory, especially with regard to the probability of lymph node involvement (degree of histological differentiation, degree of infiltration of the rectal wall, absence of palpable pararectal metastatic lymph nodes). After treatment, follow-up must be performed methodically. Moreover, in patients not older than 55, mesenteric and perirectal lymphadenectomy must be considered. At the Centre Léon Bérard (Lyon), 231 patients followed more than 5 years have been treated. The 5-year and 10-year survival rates are respectively 57 per cent and 74 per cent. The rate of local failure is 5.2 per cent. The rate of death from cancer at 5 and 10 years is 10 per cent. However intracavitary irradiation is only applicable in 10 to 15 per cent of rectal cancers. A new conservative approach has been worked out. It consists of preoperative external beam irradiation with Cobalt 60 (30 Gy in 12 days) followed 2 months later, according to the residual disease, either by radical surgery of Iridium implant. Applied to poor risk, patients this method can spare many of a permanent colostomy, without jeopardizing their chances of cure (27 cases, median age: 77 years).

Aged↗

[Primary malignant melanomas of the urethra. Apropos of 4 cases].

The authors report four cases of primary malignant melanoma of the urethra. The rarity of these lesions can lead to their mis-diagnosis. Only histological examination of a biopsy specimen stained with Fontana stain can confirm the diagnosis. These tumours have a very poor prognosis because of their tendency to locally invade the corpus cavernosus in men and the vulva and vagina in women. These lesions carry a high risk of lymph node and metastatic dissemination. For very limited tumours, the authors recommend a relatively extensive urethrectomy (2/3 of the urethra in women and amputation of the penis in men with a perineal urethrostomy) completed by interstitial irradiation with irridium 192 (6,000 rads) and inguinal lymphadenectomy. In larger tumours, with lymph node invasion, the very brief survival time makes extensive excision inappropriate. Limited palliative surgery is to be preferred. Radiotherapy and chemotherapy have no proven effectiveness.

Aged↗