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Biomedical subjects

J Muller

Publications and source records attributed to J Muller.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Appendix in a left crural herniated position: apropos of a case. Explanation by human ontogenesis].

The authors report about one case of left crural strangulation containing the appendix. The right flexure of the colon is fixed in its usual infrahepatic position. The ascending colon, on the other hand, floats, and the cecum is in a left iliac position. An ontogenic explanation is proposed, on the basis of recent anatomical work, and compared with traditional hypotheses about the evolution of the gastrointestinal tract in relation to the development of the peritoneum.

Aged↗
PubMed1993

Development of lipoprotein-like lipid particles for drug targeting: neo-high density lipoproteins.

The possibility was explored of synthesizing, from commercially available lipids, high density lipoprotein (HDL)-like particles (neo-HDL) with the same physico-chemical and biological properties as native HDL. A preparation method involving egg yolk phosphatidylcholine, cholesterol, and apoproteins from HDL led to the formation of particles with a composition, size, electrophoretic mobility, and density similar to those of discoidal HDL. In vitro experiments with isolated parenchymal liver cells showed that unlabeled HDL and neo-HDL competed for the same high affinity binding sites as did radiolabeled neo-HDL, whereas an excess of unlabeled low density lipoprotein was ineffective. In vivo experiments with radio-labeled neo-HDL indicated that neo-HDL showed a slow decay upon injection into rats, whereas the liver uptake did not exceed > 10% of the injected dose. The small additional liver uptake of radioactivity from neo-HDL, compared with HDL, was due to enhanced uptake by endothelial and Kupffer cells. Lactosylation of neo-HDL led to a markedly increased decay rate and a rapid uptake by rat liver (80% in 10 min). Parenchymal cells accounted for > 90% of the total liver uptake of radiolabeled lactosylated neo-HDL. Because the liver uptake of lactosylated 125I-neo-HDL could be blocked by preinjection of N-acetylgalactosamine, we conclude that the asialoglycoprotein receptor, which is specifically localized on parenchymal liver cells, is responsible for the avid liver uptake. With a fibroblast cell line transfected with the human asialoglycoprotein receptor, it was found that lactosylated neo-HDL binds with high affinity (Kd, 40 nM), in a galactose-specific way. It can be concluded that, with commercially available lipid components, HDL-like particles (neo-HDL) with virtually the same characteristics as found for native apolipoprotein E-free HDL can be reconstituted. Lactosylated neo-HDL, which is rapidly taken up by galactose-specific receptors on parenchymal liver cells, might be used to transport antiviral drugs specifically to parenchymal liver cells.

3T3 Cells↗
PubMed1992

Interlaboratory study of the IFCC method for alanine aminotransferase performed with use of a partly purified reference material.

We present the results of a study on performance of a reference material for alanine aminotransferase (ALT, EC 2.6.1.2) and the corresponding IFCC-approved method in an interlaboratory trial involving 13 laboratories. The ALT material was partly purified from pig heart (specific activity, 150 kU/g) and was essentially free of six potentially contaminating enzyme activities, including aspartate aminotransferase (EC 2.6.1.1). The partly purified ALT was lyophilized in a triethanolamine-buffered matrix, pH 6.4, containing bovine serum albumin and saccharose. Under these conditions, the predicted yearly loss of activity was 0.02% at 4 degrees C and < 0.01% at -20 degrees C. The final blank-corrected results of the accepted set of data gave a mean (SD) of 128.5 (5.1) U/L. The among-laboratory SD was 4.6 U/L and the within-laboratory SD was 2.0 U/L. The certified ALT catalytic concentration in the reconstituted material was 129 U/L with a 0.95 confidence interval of +/- 4 U/L.

Alanine Transaminase↗
PubMed1991

Dynamics of differentiation in human epidermoid squamous carcinoma cells (A431) with continuous, long-term gamma-IFN treatment.

We investigated the long-term effects of continuous gamma interferon (gamma-IFN) treatment on A431, a human squamous carcinoma cell line. Cells were grown in an in vitro culture system, which over time produces cohesive cell masses ("tumoroids") exhibiting three-dimensional, histotypically differentiated structures, e.g., keratin "pearls", intercellular bridges (desmosomes), elongated flattened cells (squames) and stratification. The effects of gamma-IFN on cell growth, morphology and stage of differentiation were assessed at different treatment times by light and electron microscopy and by immunohistochemical staining using antibodies to keratins 1 and 14 and to filaggrin, markers of specific stages of keratinocyte differentiation. Our results show that A431 cells have the capacity for spontaneous differentiation, that this capacity is significantly enhanced and accelerated by gamma-IFN treatment leading to terminal differentiation and extensive cell death by 2 wk. Despite continuous exposure to IFN, a small number of viable, undifferentiated cells remain. Their proliferation, evident by 3 wk, reconstitutes the tumoroid which once again contains the full range of differentiating cell types.

Biomarkers, Tumor↗
PubMed1991

Certification of an enzyme reference material for alkaline phosphatase (CRM 371).

We have produced a batch of lyophilized alkaline phosphatase (AP) for use as an enzyme reference material. The enzyme was partly purified from pig kidney to a specific activity of 400 U/mg of protein and is essentially free from contaminating enzyme activities. The kinetic properties of the preparation are very close to those of the enzyme present in human serum. The partly purified AP was lyophilized in a matrix containing bovine serum albumin (40 g/L), MgCl2, ZnCl2 and NaCl. The vial-to-vial variability with respect to the catalytic concentration of the final product was 0.008. The predicted annual relative loss of activity was less than 0.01% at -20 degrees C and 0.04% at 4 degrees C. This material was certified using the IFCC proposed method. The certification procedure involved 19 laboratories throughout the world. The certified alkaline phosphatase catalytic concentration in the reconstituted material was 254 U/L with a 0.95 confidence interval of +/- 6 U/L.

Alkaline Phosphatase↗
PubMed1991

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.

Adenocarcinoma↗
PubMed1991

Clinical, radiographic, and pathological features of symptomatic Rathke's cleft cysts.

The clinical, radiographic, and pathological findings in 155 patients with symptomatic Rathke's cleft cysts are discussed. Eight patients were treated by the authors and 147 were collected in a review of the literature. This lesion occurred more often in female than male patients by a 2:1 margin, and the mean age at presentation was 38 years. The average patient had been symptomatic for nearly 3 years at the time of treatment, with the most common symptoms and signs being pituitary dysfunction, visual disturbances, and headaches. Affected children generally were pituitary dwarfs. The sella was enlarged in 80% of cases, and the cyst was situated in both an intrasellar and a suprasellar location in 71%. Computerized tomography revealed a low-density cystic mass with capsular enhancement in one-half of the cases. A variable appearance was seen with magnetic resonance imaging. Partial excision and drainage of the cyst by the transsphenoidal approach is the recommended treatment, as the recurrence rate is low. Most symptoms and signs improved or resolved following surgery with the exception of hypopituitarism and diabetes insipidus. The cyst lining was usually composed of ciliated cuboidal or columnar epithelium. Theories as to the origin of Rathke's cleft cysts are also discussed.

Adolescent↗
PubMed1991

Relation between debrisoquine oxidation phenotype and morphological, biological, and pathological variables in a large population.

Factors affecting biological variations in debrisoquine-oxidation polymorphism were investigated in a population of 3065 unrelated supposedly healthy Caucasian subjects, ages 35 to 50 years. This population, including 1526 men and 1539 women, was used to determine whether the debrisoquine-oxidation phenotype can be related with environmental factors such as alcohol intake, smoking habits or medication; with morphological variables; or with 22 blood constituents and some pathological states. A single dose of 10 mg of debrisoquine sulfate was administered to determine the oxidation phenotype. A metabolic ratio (debrisoquine/4-hydroxydebrisoquine) of 10.0 defined a poor metabolizer [frequency of 8.2% (SD 1.0%)] in this sample. Dose recoveries of debrisoquine excretion (mean and SD) were 8.9% (11.9%) and 45.1% (32.2%) in extensive and poor metabolizers, respectively. The mean (SD) amount of debrisoquine administered that was excreted in urine as 4-hydroxydebrisoquine was 17.4% (17.3%) in extensive metabolizers and 0.5% (0.9%) in poor metabolizers. The main factors differing significantly between poor and extensive metabolizers were mean cell volume, mean corpuscular hemoglobin concentration, albumin, and ponderal index. No other blood constituents (e.g., cholesterol, glucose) differed between poor and extensive metabolizers. The lack of correlation with most of the variables tested is of interest in clinical trials, because our findings indicate that no subgroups will be required, making selection of subjects easier.

Administration, Oral↗
PubMed1990

Effects of serosal hypertonicity on water permeability in toad urinary bladder.

We studied in toad urinary bladder the effects of serosal hypertonicity on tissue water permeability, granular cell luminal membrane water permeability, and granular cell luminal membrane particle aggregates and compared them with effects of antidiuretic hormone (ADH). In tissues challenged by a hypertonic (447 mosmol/kgH2O) serosal bath, luminal membrane aggregates were structurally similar to those caused by ADH. The tissue water permeability increase induced by serosal hypertonicity was much less than that caused by a maximally stimulating concentration of ADH on tissue in isotonic serosal baths with approximately the same transmural gradient. The difference is explained not only by a reduced incidence of luminal membrane aggregates but also by an increased resistance to water movement at a postluminal membrane site. Measurements of luminal membrane water permeability showed a close correlation with luminal membrane aggregate frequency, indicating that the calculated permeability of an individual aggregate was a constant. Thus the relation of luminal membrane aggregates to tissue osmotic permeability is modified by serosal hypertonicity. Morphological examination of these tissues suggested that luminal membrane aggregates may be less stable in the absence of hormone. This was evident by the proportionally greater number of structures interpreted as aggregates captured in the process of disassembly ("patches"). Membrane depressions containing intramembrane particles ("craters") were also observed. They corresponded in terms of frequency and size to coated pits as seen in thin sections.

Animals↗
PubMed1989

Purification and characterization of two distinct forms of rat adrenal cytochrome P450(11) beta: functional and structural aspects.

It is generally accepted that the last three steps of aldosterone biosynthesis are catalyzed by a single enzyme, i.e., cytochrome P450(11) beta (P450XIB). We have previously reported that rat adrenal mitochondria may be capable of producing two forms of P450(11) beta which differ in molecular weight (49 and 51 kDa). In the present study we describe the purification, the enzymatic activities, and some structural properties of these two proteins. Using zona fasciculata mitochondria, the 51-kDa protein was purified to electrophoretic homogeneity by means of octyl-Sepharose chromatography. In a reconstituted system the protein catalyzed 18- and 11 beta-hydroxylation of deoxycorticosterone, but exhibited no 18-hydroxylation or 18-hydroxydehydrogenation of corticosterone. The 49-kDa protein was isolated from zona glomerulosa mitochondria of rats kept on a low-sodium, high-potassium regimen. Using octyl-Sepharose chromatography, it could be separated from the 51-kDa protein. A reconstituted eluate fraction, containing the 49-kDa protein, converted deoxycorticosterone not only to 18-OH-deoxycorticosterone and corticosterone, but also to 18-OH-corticosterone and aldosterone. These findings indicate that the rat adrenal cortex is capable of producing two distinct forms of active cytochrome P450(11) beta. A structural relationship of the 49- and 51-kDa proteins was indicated by experiments involving limited proteolysis. Thus, digestion with alpha-chymotrypsin and V8-protease yielded very similar peptide maps for both proteins. During potassium repletion of potassium-deficient rats, the disappearance of the active 51-kDa protein coincided with the appearance of the 49-kDa protein. These results are suggestive of a post-translational processing mechanism converting the 51-kDa protein into the smaller 49-kDa form. However, the 49-kDa protein might also be encoded by a distinct gene, regulated separately depending on the physiological conditions.

Adrenal Cortex↗
PubMed1989

Comparative study of neuroma formation in the rat sciatic nerve after CO2 laser and scalpel neurectomy in combination with milliwatt CO2 laser "sealing".

Nerve transections of rat sciatic nerves were performed to compare scalpel neurectomy to CO2 laser neurectomy. Additionally, the effect of milliwatt CO2 laser application to the proximal nerve ending was studied. Animals were sacrificed at 1 to 9 weeks, and the neuromas were examined histologically and measured. Scalpel transections produced typical neuromas. Laser transections produced neuromas characterized by multinucleated giant cells and carbonaceous debris. There was no difference in the size of the neuromas produced by either method of transection. Milliwatt CO2 laser application to the proximal stump did not affect the size or histology of resultant neuroma formation regardless of the method of transection.

Animals↗
PubMed1989

Regulation of mammalian melanogenesis by tyrosinase inhibition.

Melanocyte stimulating hormone (MSH) specifically induces differentiation of mammalian melanocytes. To further define the biochemical events elicited by this stimulus, we have cloned murine melanoma cells which are either highly responsive or nonresponsive to MSH, and have examined their ultrastructural appearance, their melanogenic activities, and also their expression of tyrosinase. We have found that the basal levels of melanogenic activity in pigmented and nonpigmented cells correlate with expression of surface MSH receptors rather than with production of tyrosinase. Nonpigmented cells produce a potent, highly stable inhibitor of melanogenesis; this inhibitor acts directly on tyrosinase to dramatically and abruptly suppress melanin production. This posttranslational control of tyrosinase activity may represent a critical regulatory point in mammalian pigmentation.

Animals↗
PubMed1989

Variability of cellular responsiveness to ADH stimulation in toad urinary bladder.

The hydrosmotic response of toad bladder to antidiuretic hormone (ADH) is quantitatively linked to the induced fusion of aggrephores with, and the appearance of aggregates of tightly packed intramembrane particles in the luminal membrane of granular cells. We used these morphological indexes of hormonally induced cell activation 1) to assess the variability of individual cell responsiveness to a maximally stimulating concentration of ADH and 2) to compare cell response patterns in paired tissues where the extent of whole tissue stimulation, as evidenced by transtissue water flow, was either maximal or submaximal. The results indicate that individual cell responsiveness within the same tissue to standardized maximal ADH treatment varies between two- and sevenfold, depending on the morphological endpoint measured. Furthermore, based on skewness in endpoint distribution, this variability appears to reflect inherent heterogeneity of granular cell reactivity to hormone. In relation to proportional tissue responses elicited by different stimulating concentrations of ADH, our observations of luminal membrane aggregate incidence suggest that the responding cells, whatever their sensitivity, participate in a graded, rather than "all-or-none," "on-off" manner.

Animals↗