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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 955 records · Page 53Linked to original sources

Effect of insulin treatment on osteocalcin levels in diabetic children and adolescents.

To investigate bone mineral metabolism in insulin-dependent diabetes mellitus, serum osteocalcin, a marker of bone formation, was measured in 31 diabetic children at onset of disease and 15 days after metabolic improvement by insulin therapy. As a control group for osteocalcin levels we studied 31 healthy sex- and age-matched children. Mean values of serum osteocalcin at onset of diabetes were significantly lower than in control group (p < 0.001), but we did not find any difference after 15 days of insulin therapy. Osteocalcin and parathyroid hormone concentrations were significantly greater after 15 days of insulin treatment than at onset of disease (p < 0.001 and p < 0.01, respectively). The osteocalcin levels were negatively correlated both with fructosamine and with glycosylated hemoglobin (p < 0.01 and p < 0.001, respectively), and positively correlated with the degree of metabolic acidosis at onset (p < 0.05). Therefore we postulate that during glycometabolic imbalance there is a decrease in bone turnover that could be one of the etiological factors of diabetic osteopenia.

Child↗

Repair of early cholesterol-induced aortic lesions in rabbits after withdrawal from short-term atherogenic diet. Scanning electron-microscopical (SEM) and transmission electron-microscopical (TEM) observations.

Signs of repair of early atherosclerotic lesions after withdrawal of rabbits from a short-term atherogenic diet have been observed by means of scanning and transmission electron microscopy. The endothelial lining was lacking over large portions of the plaques during early atherogenesis. During the regression phase, hematic cholesterol values returned to normal, the smooth muscle cells of the plaques lost a large part of the lipids they had accumulated, while the surface of the plaques was covered by a continuous layer of endothelial cells.

Animals↗

Entamoeba histolytica infections in flight personnel of an international airline.

A cohort of 99 subjects, members of the flight staff of Lufthansa German airlines, all infected with Entamoeba histolytica, were followed over a period of 2.5 years to monitor their clinical and parasitological status. All but 4 of the subjects were infected with non-pathogenic zymodemes of E. histolytica and had negative amoebic serology, and most were clinically well. One male heterosexual carrying a pathogenic zymodeme was found, despite massive treatment regimes, to carry the infection persistently for 12 months. Most non-pathogenic infections were left untreated.

Aircraft↗

Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during differentiation in HL-60 leukemia cells.

The study was undertaken to elucidate the regulatory roles of GMP reductase (GMPR) and IMP dehydrogenase (IMPDH) on purine interconversion during differentiation. Treatment of HL-60 cells with retinoic acid (1 microM) induced granulocytic differentiation which was accompanied with a 2.4-fold increase in GMPR and 55% decrease in IMPDH activities. Maturation induced by 12-O-tetradecanoylphorbol 13-acetate or dimethylsulfoxide was also associated with similar reciprocal alterations. Incubation with guanosine (200 microM), which expands the guanine nucleotide pool, elevated GMPR (1.9-fold) and decreased IMPDH (73%) activities. The synchronous and opposing alterations in GMPR and IMPDH activities should amplify the metabolic response due to differentiation or guanylate pool expansion.

Adenine Nucleotides↗

Estimation of the polarity of the protein interior by optical spectroscopy.

Crystallographic studies of myoglobin have shown that the haem pocket is lined with nonpolar amino-acid residues. In order to estimate the true polarity of the interior of proteins, certain studies have used bound fluorophores, the spectroscopic properties of which reflect the polarity of their environment. These studies have most often used 1-amino-8-naphthalene sulphonate (ANS) as a probe, but a more suitable probe, in principle, is 6-propionyl 2-(N,N-dimethyl)aminonaphthalene (PRODAN). We have synthesized a molecule with the advantageous spectroscopic properties of PRODAN but with a higher affinity for apomyogloblin: 2'-(N,N-dimethyl)amino-6-naphthopyl-4-trans-cyclohexanoic acid (DANCA), and report here its use to determine the polarity of the myoglobin haem pocket. Our results show that the pocket is actually a polar environment, and the polarity can be accounted for by peptide amide dipoles.

Animals↗

Distribution of metals in human lung: analysis by particle induced x-ray emission.

Thirty-five lung pairs obtained during autopsy from randomly selected patients were investigated by particle induced X-ray emission for overall and regional elemental content determination. In each case the interbronchial lymph node was simultaneously processed. While homogenous distribution has been consistently observed for potassium, calcium, iron, copper, zinc, and rubidium, a very different distribution was recorded for titanium, chromium, nickel, and strontium. The significance of these results is discussed with regard to pollution hazards. Regional accumulation of this second group of elements seems to be related to air pollution peculiar to Liège. Advantages and limitations of the technique and the need for further research are stressed.

Adult↗

Nonfibrous mineralogical analysis of bronchoalveolar lavage fluid from blast-furnace workers.

Steelworkers are exposed to many pollutants, and they are at risk for developing lung cancer. We demonstrated previously that steelworkers may be subject to an occult exposure to amphiboles in the plant environment. In the current study, we further analyzed bronchoalveolar lavage fluid of steelworkers by measuring intramacrophagic trace-metal content and nonfibrous mineral particles, using the particle-induced x-ray emission method and electron microscopy, respectively. Forty-seven blast-furnace workers and 45 healthy white-collar workers volunteered for this study. Significantly increased levels of iron, titanium, zinc, and bromine were found in the steelworkers, and levels of lead, chromium, arsenic, and strontium tended to increase in the macrophages and bronchoalveolar lavage fluid of the steelworkers. Nonfibrous particles, including illite, kaolinite, talc, chlorite, amorphous silica, quartz, iron (compounds), and titanium hydroxide, were found in both groups, but the particle number per ml bronchoalveolar lavage fluid (particularly iron hydroxides and silicates) was more pronounced in blast-furnace workers. These elements and particles may act synergistically with other occupational carcinogens and cigarette smoke, the result of which may be an increased incidence of lung cancer in the ironsteel industry.

Adult↗

Secular change in height in Austria: an effect of population stratification?

The records of height on some 700,000 18-year-old Austrian males, called for examination as to their fitness for conscription, were analysed. The data covered 14 conscription years (1980-93), representing males born in the years 1962-75. The sample covered over 90% of the total male population of those cohorts in Austria. The data were analysed by birth year to show the secular trend in 18-year-old stature and its rate, which overall amounted to 0.53 cm/decade. Analysis by urban-rural residence showed that both participated in the trend, but that the urban-rural differences were appreciably less than the differences between the types of school the young men had attended. The rate of increase over the 14 years was less within each of the eight subgroups (urban-rural, four school categories). It is argued that the secular trend in height that has occurred is largely attributable to the change in social stratification, as evidenced by the changed proportion of subjects who attended schools of different types.

Adolescent↗

Biochemical strategy of hepatomas.

An insight into the ordered pattern of enzymatic and biochemical imbalance of cancer cells was made possible, at least in part, by the molecular correlation concept, the concept of key enzymes, and the use of biological model systems. With these approaches the pattern of gene expression in neoplasia can be studied in terms of the activities of key enzymes and their linking with neoplastic transformation and progression. An ordered pattern of biochemical imbalance was recognized in carbohydrate, pentose phosphate, purine, pyrimidine, DNA, and polyamine metabolism and in other biochemical areas. Current work is directed to clarifying the enzymology and metabolic pattern of thymidine metabolism and CTP biosynthesis since these areas are of particular importance in selective chemotherapy and rescue. The activities of key enzymes in thymidine metabolism have been correlated with the growth rates in a spectrum of hepatomas. Increases in the activities of four key enzymes in CTP biosynthesis appear to be specific to neoplasia because no similar pattern was observed in the normal adult resting or regenerating liver or in the fetal and developing liver. The overall pattern discovered in transplantable rat hepatomas applies to other rodent tumors. It is of particular importance that the pattern of biochemical imbalance is also applicable to human hepatocellular carcinomas. With the recognition of the ordered pattern of reprogramming of gene expression in hepatomas, the path is open for the development of sensitive assays for biochemical diagnosis of liver tumors and for a rational design of selective chemotherapy and rescue.

Animals↗

Natural history of TCDD-induced liver lesions in rats as observed by transmission electron microscopy during a 32-week period after a single intraperitoneal injection.

Forty-two male rats were injected with a single intraperitoneal dose of TCDD in acetone and corn oil and sacrificed after 2, 4, 8, 16, 24, and 32 weeks, to study the long-term effects of a single injection. The liver lesions become progressively worse up to the 16th week and appear thereafter to slowly regress.

Animals↗

Animal model of TIA: an experimental study with intracarotid ADP infusion in rabbits.

Adenosine diphosphate (8 mg per minute for five minutes) was infused into the carotid artery of 63 rabbits. The effects were twofold: systemic hypotension and platelet aggregation in the cerebral circulation. As a consequence of the last effect, platelet emboli were produced which occluded cerebral arteries in a number and size sufficient to cause cerebral ischemia. Areas of focal ischemia were observed through a cranial window, and documented with antipyrine autoradiography. Platelet thrombi were almost entirely transient, being fragmented and removed within a very short time of cessation of ADP infusion. Consequently, no permanent tissue damage ensued. This experimental model approaches the spontaneous transient ischemia attacks (TIAs) in man, demonstrating that these can be caused by pure platelet emboli. A high cholesterol diet administered for two months prior to ADP infusion did not enhance the effect of the procedure or make the platelet aggregation and the following ischemia longer in duration or more severe.

Adenosine Diphosphate↗

Total parenteral nutrition with and without fat as substrate for growth of rats and transplanted hepatocarcinoma.

Differential effects of total parenteral nutrition (TPN) on host nutrition and growth of cancer are unclear. Growth of adult ACI-N rats bearing transplanted Morris hepatocarcinoma no. 3924A given TPN with or without fat was studied in comparison with Purina Chow-fed, fasting, and semifasting (either amino acid or dextrose alone) rats over 5 days. The isocaloric, isonitrogenous TPN regimens with or without fat maintained body weight and nitrogen balance of cancer-bearing rats equally well. When compared with Chow-fed rats, the volume of the cancer, its weight, doubling time, protein content, and incorporation of thymidine into DNA were similar in rats given TPN either with or without fat. Although the volume of the cancer decreased in fasting and semifasting rats, the nutritional status of the host was also impaired. Administration of TPN to cancer-bearing rats was associated with an abnormal increase in serum lactic acid level, which was not ameliorated by the use of fat to reduce the carbohydrate load. Although TPN with and without fat maintains the nutritional status, hepatomegaly and hepatic steatosis limit the administration of carbohydrate and fat as energy substrates in this system.

Animals↗

Measurement of urinary iodine excretion to reveal iodine excess in neonatal transient hypothyroidism.

This study was undertaken to confirm the importance of iodine excess in neonatal transient hypothyroidism. In 30 transient hypothyroid newborns at screening we measured urinary iodine excretion and TSH. They were divided into two groups: group A consisted of 21 newborns who had been exposed to iodine; group B of 9 non-exposed newborns. The two groups were significantly different only for median urinary iodine excretion (p = 0.001). In 61.5% of newborns of group A, iodine exposure caused iodine excess (urinary iodine excretion higher than 185 micrograms/l); this correlated with a higher prevalence of prematurity and a lower mean gestational age. Clinical records should reveal iodine exposure, but only urinary iodine excretion shows iodine excess. We suggest that evaluation at birth of urinary iodine excretion in every newborn with high TSH could help in predicting a good prognosis, since hypothyroidism due to the Wolff-Chaikoff effect is always spontaneously reversible, even if treatment may be suggested.

Female↗

Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells.

PURPOSE: Tamoxifen and genistein were tested for synergism in estrogen receptor- negative human breast carcinoma MDA-MB-435 cells because the two compounds decrease signal transduction activity through different biochemical mechanisms and arrest the cell cycle at different phases. MATERIALS AND METHODS: The combination effect of tamoxifen and genistein on signal transduction was determined by measuring IP3 concentrations and on cell proliferation and colony formation by growth inhibition assay and clonogenic assay. RESULTS: In growth inhibition assays, for tamoxifen and genistein in the carcinoma cells the IC50s were (mean +/- SE) 17 +/- 0.9 and 27 +/- 1.6 microM; in clonogenic assays the LC50s were 0.9 +/- 0.4 and 12.5 +/- 1.1 microM, respectively. When tamoxifen and genistein were simultaneously added to the cells, synergism was observed in growth inhibition, in cytotoxicity and in the reduction of inositol 1,4,5-trisphosphate concentration. CONCLUSION: The synergistic down-regulation of signal transduction by tamoxifen and genistein may explain, in part at least, the synergistic antiproliferative and cytotoxic actions of the two compounds. The synergism of tamoxifen and genistein may be of interest in the clinical treatment of breast carcinoma.

Antineoplastic Agents, Hormonal↗