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Biomedical subjects

E Wolf

Publications and source records attributed to E Wolf.

At least 235 records · Page 13Linked to original sources
PubMed1991

Accelerated growth and visceral lesions in transgenic mice expressing foreign genes of the growth hormone family: an overview.

Effects of growth hormone (GH) overproduction were studied in transgenic mice expressing murine metallothionein I-GH fusion genes. The most obvious consequence was the acceleration of growth, which led to substantial increases in body weight of up to more than twice that seen in controls. Growth of the internal organs was stimulated, with hepatomegaly and nephromegaly as the most prominent features. GH transgene expression was also reflected in increased skeletal growth which affected various bones to different extents. The mean life-span of human GH transgenic mice with serum levels of hGH ranging from 3 x 10(3) to 9 x 10(5) ng/ml was drastically reduced at 160 days in both sexes. Severe renal lesions were the primary cause of the decrease in life expectancy and were characterized by marked nephron atrophy, obsolescence of numerous glomeruli, and a massive cystic dilation of the tubules. Initial changes involved the glomeruli, which showed significant enlargement and sclerotic lesions. The liver exhibited a pronounced hepatocellularmegaly and progressive degenerative as well as hyperplastic changes. One-third of the hGH transgenic animals displayed myocardial fibrosis. Hepatocellular carcinoma was found in bovine GH transgenic mice older than 12 months. Our observations are compared with results of other investigators.

Animals↗
PubMed1991

Color discrimination and accuracy of blood glucose self-monitoring in type I diabetic patients.

OBJECTIVE: To determine the importance of color discrimination ability regarding accuracy in the self-monitoring of blood glucose. RESEARCH DESIGN AND METHODS: Two hundred two insulin-dependent (type I) diabetic patients performed the Fansworth-Munsell 100-hue test and a second group of 159 type I diabetic patients performed a new Düsseldorf 26-hue test. Error scores in both tests were compared with error scores of patients' self-monitoring of blood glucose measurements with Chemstrip Haemoglucotest 20-800 strips. RESULTS: Color discrimination ability decreased with age, diabetes duration, and presence of retinopathy. It was independent of the degree of glycemia and accuracy of self-monitoring of blood glucose. CONCLUSIONS: Impaired color vision by itself is no reason to abandon self-monitoring of blood glucose with visually read strips.

Adult↗
PubMed1991

Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. I. Body weight gain and external body dimensions.

Body weight gain and external body dimensions of MT-hGH transgenic mice were compared with mice (NMRI) selected for high 8-week body weight (N8) and unselected controls derived from the NMRI strain (Pop). The growth curves from day 30 to 120 of transgenic mice exhibited a significantly steeper slope than those of male and female controls and of female N8 mice and did not show sex-related differences. The continuous pattern of GH secretion in transgenic mice is discussed as a possible reason for this phenomenon. Body weight gain of transgenic mice did not significantly exceed that of male N8 mice. None of the groups showed an obvious prolongation of the period of rapid daily weight gain. Maximum body weights of male and female transgenic mice were significantly higher than those of sex-matched controls but not of N8 mice. A drastic loss of body weight of about 25% of the maximum value was observed in the transgenic group prior to death. External body dimensions were largest in MT-hGH transgenic animals, followed by N8 mice and controls. In addition to these absolute measurements, values were related to the cube root of maximum body weight of the same animal. This is the first study that provides a comparative analysis of the effects of GH gene transfer and selection for body weight gain on body growth of mice derived from an outbred strain.

Animals↗
PubMed1991

Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. II. Skeleton.

Growth hormone and mechanical loading are known to be important factors influencing bone growth. We have measured proportions of the skull and the postcranial skeleton of metallothionein-human growth hormone (MT-hGH) transgenic mice expressing high levels of hGH in their serum, of NMRI mice being large as a result of selection for high 8-week body weight (N8), and of unselected controls (Pop) derived from the NMRI strain. Absolute bony dimensions of transgenic mice were as a rule significantly larger than those of controls, the differences ranging between 3% and 32% in males and from 6% to 28% in females. By contrast, the enlargement of skeletal dimensions of N8 mice did not exceed 10% and was restricted to distinct bones. When related to the cube root of maximum body weight of the same animal, bones of controls were as a rule larger than those of N8 and MT-hGH transgenic mice. A detailed analysis of bony dimensions of GH transgenic mice and of mice selected for high body weight was carried out to judge the effects of GH overexpression and mechanical loading due to increased body weight on bone growth. The fact that bones of transgenics were as a rule larger than those of selected mice in spite of both groups reaching similar maximum body weights, suggests that skeletal gigantism in MT-hGH transgenic mice can only in part be a result of increased body weight.

Animals↗
PubMed1991

Expression of metallothionein-human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism.

Transgenic mice harbouring mouse metallothionein I-human growth hormone (MT-hGH) fusion genes were produced using the microinjection technique. The bones of adult MT-hGH transgenic mice, which continuously expressed high levels of hGH in their serum, and age-matched controls lacking detectable concentrations of hGH were measured microscopically. In addition to analyzing absolute skeletal dimensions, measurements were related to the cube root of the maximum body weight of the same animal. Absolute values obtained from transgenic mice were significantly higher than those obtained from controls for most of the defined measurements. However, the increase in skeletal dimensions was mostly not as pronounced as the increase in body weight and all bones were not affected to the same extent. There was no significant correlation between the serum GH concentration in individual mice and their degree of bony overgrowth. A disproportionate skeletal gigantism in MT-hGH transgenic mice may result from time differences in epiphyseal union of various bones of both sexes as well as differences in mechanical bone loading due to a drastically increased body weight. Individual concentrations of locally produced tissue insulin-like growth factor I (IGF I) might also play a role. Possible effects of these factors are discussed. The results presented in this study show that MT-hGH transgenic mice provide a powerful tool for the investigation of hormonal regulation of bone growth.

Amino Acid Sequence↗
PubMed1991

[Unexpected transgene expression of a mammary-specific growth hormone gene construct in Bergmann glial cells of the mouse].

Pronuclear microinjection was used to produce transgenic mice harboring gene constructs, in which 110 base pairs (WAP1) or 2.4 kilobases (WAP2) of the 5' flanking sequences of the whey acidic protein (WAP) gene were fused to human growth hormone (hGH)-coding sequences. Female WAP-hGH transgenic mice expressed the transgenes in the mammary gland, the expression of the WAP2-hGH transgene mirroring that of the endogenous WAP gene. When other organs were examined, high level expression of hGH was observed in the brains of WAP2-hGH transgenic mice. Using in situ hybridization and immunohistochemistry, hGH expression from the transgene was seen to occur specifically in Bergmann glia cells. While normally neither WAP nor hGH is expressed in this type of cell, it appears that a combination of the regulatory region of the WAP gene and the hGH structural gene results in a novel tissue specificity in Bergmann glia cells.

Animals↗
PubMed1989

Spatial distribution of pre- and postsynaptic sites of axon terminals in the dorsal horn of the frog spinal cord.

Axon terminals which could be interpreted as dorsal root boutons, were photographed from a series of 98 ultrathin sections with a Jeol 100B electron microscope. A total of 13 boutons were recovered for computer reconstruction. Two of them were terminal boutons, eight en passant boutons and three boutons were only partially recovered. All boutons contained multiple synaptic sites (maximum 33 and minimum seven) at which axodendritic and axoaxonic synapses were established. Axodendritic synapses were of the asymmetric type and they were directed toward adjacent dendrites. In axoaxonic synapses, which were of the symmetric type, the boutons were invariably on the postsynaptic side. Among the presynaptic profiles axons with spherical and pleomorphic vesicles and dendrites with flattened vesicles could be discerned. On average, each 2.67-microns2 bouton surface area contained one presynaptic site at which an axodendritic synapse was established, and each 7-microns2 surface area contained one postsynaptic site for an axoaxonic (or dendroaxonic) contact. A tendency of grouping of synaptic sites was observed. Distance measurements between the closest neighbours of all synaptic sites were made in four combinations in boutons with the original and with a random distribution of synaptic sites. The arithmetic mean of distances measured between the presynaptic and the closest postsynaptic sites was almost twice as big as that measured in the reverse direction. The difference between these values became greatly reduced in the case of random distribution. The arithmetic mean of distances between the closest neighbours of presynaptic sites was about the same as that between the closest neighbours of postsynaptic sites. This latter value was considerably increased with randomly distributed synaptic sites. The results suggest a non-random distribution of synaptic sites on the surface of boutons. The analysis of cluster formation of synaptic sites performed with a numerical taxonomy technique revealed that the majority of the 153 synaptic sites were comprised in 27 clusters containing both pre- and postsynaptic sites within the 1-micron similarity level. All postsynaptic sites were within 1 micron of one or more presynaptic sites. On the basis of the assumption that the postsynaptic sites are occupied by inhibitory axoaxonic synapses, it is suggested that the transmitter release from the presynaptic sites can be individually controlled in this structural arrangement. A probable mechanism of this function may be the passive invasion of the bouton by the impulse propagating actively along the dorsal root fibre.

Animals↗
PubMed1989

Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function.

Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 +/- 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 +/- 1.2 days after initial therapy. Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC group than in the heparin group. This was true for the entire study group (0.53 +/- 0.13 versus 0.47 +/- 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 +/- 0.13 versus 0.40 +/- 0.11; p = 0.04 and 0.56 +/- 0.10 versus 0.51 +/- 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p less than 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -0.73, p less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated patients had died. In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.

Acute Disease↗
PubMed1989

A cross-sectional ecological analysis of blood pressure and its determinants in eleven Pacific populations.

A cross-sectional interpopulation analysis of blood pressure and its determinants was conducted with the data collected during epidemiologic surveys in 11 Pacific island populations from 1975 to 1981. In each of these populations, the mean arterial blood pressure increased with age; the overall blood pressure levels differed among the populations. The multivariate analyses suggest that dietary factors that result in differences in body mass, plasma cholesterol, and glucose intolerance contribute considerably to interpopulation differences in blood pressure. The impact of these differences in effects of dietary factors on interpopulation blood pressure seemed to be uniform, even though the overall levels of each of these three variables differed significantly among the populations. This study of blood pressure data, accrued from 6224 men and 7029 women aged 20-79 years, supports the hypothesis that dietary factors strongly contribute to high blood pressure as well as to interpopulation differences in the prevalence of hypertension. We propose using these data in planning programs for prevention and control of hypertension in the Pacific countries.

Adult↗