[Genetics of osteoporosis].
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Age Factors↗
Biomedical subjects
R Ebert
Publications and source records attributed to R Ebert.
Reversal of bone loss in mice by nongenotropic signaling of sex steroids.
We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].
Animals↗
Conducting research on the Internet--Part II.
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Humans↗
Reverse transcriptase-polymerase chain reaction analysis of thyrocyte-relevant genes in fine-needle aspiration biopsies of the human thyroid.
Currently, fine-needle aspiration cytology is a valuable tool in the routine diagnosis of suspicious thyroid nodules. We present a very sensitive method for the molecular analysis of the expression of several genes important for normal thyroid function in parallel to the cytological diagnosis. We adapted reverse transcriptase polymerase chain reaction (RT-PCR) to amplify thyroid-typical mRNAs in samples of thyroid carcinoma cells as small as those obtained by fine-needle aspiration biopsy (FNAB), ie, 100-1000 cells, and applied this procedure to four routinely taken FNABs. Gene products such as thyroglobulin (Tg), thyroid-stimulating hormone-receptor (TSHr), sodium/iodide-symporter (NIS), type I iodothyronine-5'-deiodinase (DI), and type II iodothyronine-5'-deiodinase (DII) were analyzed. To establish RT-PCR protocols, serial dilutions of follicular thyroid carcinoma cells, FTC-133, which express these genes at low levels, were initially used for RNA isolation. Successful RNA isolation and reverse transcription were checked by the amplification of beta-actin mRNA. We detected the mRNAs coding for Tg in as little as 10 cells, for NIS in 100 cells, and for TSHr, DI, and DII in 10,000 cells. After preparing cytological smears of four routinely taken FNABs, all above-mentioned thyroid-typical mRNAs were observed by using the material remaining in the needle for RNA isolation followed by RT-PCR. This method offers the possibility of obtaining two different types of information from the same routinely taken thyroid FNAB: the cytological diagnosis and the expression pattern of several diagnostically relevant genes. Therefore, a more specific diagnosis could be rendered in the preoperative state, and may lead to more specific therapy.
Biopsy, Needle↗
Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature.
Low level chromosome mosaicism found at amniocentesis is problematic for clinicians and patients. We report prenatal diagnosis of a fetus with a rare karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation. Careful evaluation of multiple pieces of fetal parts and placenta revealed one abnormal finding: a single umbilical artery. Cytogenetic metaphase and fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal lung, heart, placenta, and skin revealed the presence of the trisomic line in all tissues. Molecular analysis demonstrated that the origin of the extra chromosome 15 was maternal, the error most likely occurred in meiosis I and the diploid line was of biparental inheritance. This case report discusses the associated findings in this fetus and reviews the literature describing other cases of mosaic trisomy 15.
Amniocentesis↗
[Differentiated prognosis in the colicky horse].
In a retrospective study on 271 horses with colic the prediction about the outcome of the disease was made by a discriminating analysis. The best combination of quantitative prognostic parameters was capillary refill time, hematocrit, lactate and anion gap, with 90% correct predictions. In comparison with individually prognostic parameters, the combined prognosis constantly reached a higher percentage of correct predictions, the exact value resulting in 89%. Moreover, survival was better predictable than death.
Acid-Base Equilibrium↗
Species differences in the biotransformation of ethyl chloride. I. Cytochrome P450-dependent metabolism.
Groups of male and female F-344 rats and B6C3F1 mice were exposed to 15,000 ppm ethyl chloride (monochloroethane, ECL) or to air for 5 days (6 h/day). In this report, features of the P450-dependent ECL metabolism in the animals are described. A concurrent report describes the in vitro and in vivo features of the GSH-dependent ECL metabolism (Fedtke et al. 1994). ECL is oxidatively dechlorinated in an NADPH- and O2-dependent reaction, resulting in the formation of acetaldehyde (AC). The oxidative ECL metabolism rates in microsomal incubations were measured. The results indicated induction of the oxidative ECL metabolism by ECL itself in mice and female rats. The hydroxylation of p-nitrophenol, which was used as an indicator of P450IIE1 activity, was also induced in microsomal incubations from ECL-exposed mice and female rats, but, corresponding to the ECL metabolism, not in male rats. In contrast, catalytic activities related to P450IA and IIB subfamilies were not induced by ECL treatment. Additional experiments with the P450IIE1-specific inhibitor 3-amino-1,2,4-triazole and induction experiments with acetone, phenobarbital and methylcholanthrene confirmed that the isoenzyme mainly involved in the dechlorination reaction is cytochrome P450IIE1. AC was not detected in serum of ECL exposed animals and only slightly enhanced amounts were detected in urine samples from ECL exposed mice, reflecting the high capacities of the AC metabolizing pathways in vivo. The data are discussed with regard to the results of a 2-year bioassay with F-344 rats and B6C3F1 mice exposed to 15,000 ppm ECL (NTP 1989a).(ABSTRACT TRUNCATED AT 250 WORDS)
Acetaldehyde↗
Species differences in the biotransformation of ethyl chloride. II. GSH-dependent metabolism.
Groups of male and female F-344 rats and B6C3F1 mice were exposed to 15,000 ppm ethyl chloride (monochloroethane, ECL) or to air for 5 days (6 h/day). In this report, features of GSH-dependent ECL metabolism in the animals are described. A concurrent report describes the features of the cytochrome P450-dependent oxidative ECL metabolism (Fedtke et al. 1994). ECL conjugation to GSH in hepatic cytosolic fractions was catalyzed by GSH S-transferases. The specific activities were 0.16 +/- 0.03 and 0.17 +/- 0.01 nmol ECL conjugated/(min mg protein) in air treated male and female F-344 rats, respectively. These activities were not significantly altered by the ECL treatment. Compared with rats, the GSH-transferase activities towards ECL were generally higher in male and female B6C3F1 mice (0.71 +/- 0.19 and 1.01 +/- 0.19, respectively) and were slightly decreased by ECL treatment. The ECL conjugation to GSH resulted in a marked reduction of the GSH concentration in the lung and the uterus after 5 days of exposure. In contrast, liver and kidney GSH concentrations were affected only to a minor degree. Formed S-ethyl-glutathione was converted to the mercapturic acid S-ethyl-N-acetyl-L-cysteine (SENACys), which was detected in the urine of both species. In addition, the non-acetylated intermediate S-ethyl-L-cysteine (SECys) was excreted in mouse urine but not in rat urine. The cumulative amounts of SENACys and SECys excreted after 5 days were up to fivefold higher in mice than in rats and the excretion kinetics were species specific.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
Genotoxicity studies with chloroethane.
In a recent 2-year inhalation study with F344 rats and B6C3F1 mice conducted as part of the U.S. National Toxicology Program (NTP, 1989), chloroethane (ECl) at an exposure concentration of 15,000 ppm induced a high incidence of endometrial uterine carcinomas only in female mice but not in rats, leading to the conclusion of "clear evidence of carcinogenicity" for the mouse. In order to elucidate whether a genotoxic effect may be a critical factor for the carcinogenicity of ECl in the mouse, we have performed three genotoxicity tests: (1) in vitro HPRT test with CHO cells according to a specially developed gas protocol, (2) in vivo/in vitro UDS with female B6C3F1 mice at an exposure concentration of 25,000 ppm (6 h/day, 3 days), (3) in vivo micronucleus assay with male and female B6C3F1 mice exposed to 25,000 ppm ECl according to the same schedule. In the in vitro HPRT test a mutagenic potential of ECl was detected in the presence as well as in the absence of S9 mix. In contrast, both in vivo test systems failed to detect any indications of genotoxicity of chloroethane at an exposure concentration even higher than that of the NTP study. It is suggested that in vivo the genotoxic potential of ECl is so low that an assumed genotoxic damage is below the detection limit of the test systems used. This leads to the conclusion that genotoxicity may not be a key factor in the induction of the uterine carcinomas in the B6C3F1 mouse.
Animals↗
Treatment of skin defects using suspensions of in vitro cultured keratinocytes.
The in vitro cultivation of keratinocytes and their application in the form of confluent sheets to cover various kinds of skin defects involves a number of problematical steps which could be improved by using single cell suspensions instead. Therefore we developed a method to apply keratinocytes suspended as single cells in a fibrin gel. By testing the feasibility of this method in different experimental animal models we found that it facilitates cultivation as well as application of the cells, moreover, this method allows a much more flexible use of the cells, i.e. it is easier to consider the clinical condition of the patient than by the conventional method.
Animals↗
Varieties of disgust faces and the structure of disgust.
In 3 facial expression identification studies, college students matched a variety of disgust faces to verbally described eliciting situations. The faces depicted specific muscle action movements in accordance with P. Ekman and W. V. Friesen's (1978) Facial Action Coding System. The nose wrinkle is associated with either irritating or offensive smells and, to some extent, bad tastes. Gape and tongue extrusion are associated primarily with what we call core or food-offense disgust and also oral irritation. The broader range of disgust elicitors, including stimuli that remind humans of their animal origins (e.g., body boundary violations, inappropriate sex, poor hygiene, and death), a variety of aversive interpersonal contacts, and certain moral offenses are associated primarily with the raised upper lip. The results support a theory of disgust that posits its origin as a response to bad tastes and maps its evolution onto a moral emotion.
Adult↗
The RB gene locates on chromosome 15 at band 15q13 in the Syrian hamster.
The retinoblastoma susceptibility gene, which encodes a nuclear phosphoprotein (Rb), plays an important role in cell-cycle progression in both normal development and tumorigenesis. Using a Syrian hamster cDNA probe homologous to the human retinoblastoma gene (RB), we have localized the gene to chromosome band 15q13 by conventional in situ hybridization.
Animals↗
[Prognostic parameters in equine colic].
A retrospective study was performed on 271 horses with colic referred to the I. Medizinische Tierklinik within a period of 2 years, to examine the prognostic value of different clinical and diagnostic laboratory parameters by Student's t-test and the Chi-quadratic test. The following quantitative parameters presented a highly significant prognostic value (P < 0.0001): capillary refill time, pulse rate, heart rate, respiratory rate, hematocrit, hemoglobin concentration, blood lactate, base excess and anion gap. The intensity of colic signs, the degree of disturbance of the patient's general condition, the colour of the oral mucosa, the pulse quality as well as peristalsis proved to be qualitative variables with the greatest prognostic importance (P < 0.00001).
Acid-Base Equilibrium↗
Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.
In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.
Blood Glucose↗
Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations.
Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1-(7-36) amide (GLP-1) are glucose-dependent insulinotropic gut hormones that may explain the greater insulin secretory response with oral compared to i.v. glucose (incretin effect). To study their individual and combined contributions, in eight healthy volunteers, on separate occasions, synthetic human GIP (1 pmol/kg.min) and/or GLP-1 (0.3 pmol/kg.min) or placebo were infused i.v. (-30 to 120 min), while at 0 min, a glucose infusion "isoglycemic" to the profile after an oral glucose load of 50 g/400 mL was started. After the administration of 50 g oral glucose, immunoreactive GIP rose several-fold to 337 +/- 43 pmol/L, while there was only a transient (10-30 min) and moderate increment in immunoreactive GLP-1 (from basal, 25-30, to 41 +/- 4 pmol/L). Isoglycemic i.v. glucose infusions led to smaller B-cell responses (estimated incretin effect, 41 +/- 5%). With single infusions of GIP or GLP-1 (circulating concentrations, 464 +/- 73 and 54 +/- 3 pmol/L, respectively), B-cell responses were significantly augmented compared to i.v. glucose alone and were no longer significantly different from those after oral glucose. The combination of GIP and GLP-1 led to B-cell responses that were significantly higher than those with either hormone alone (additive mode of cooperation). Plasma GIP concentrations were similar after endogenous secretion (oral glucose) and i.v. infusion, while exogenously administered GLP-1 led to plasma levels that were maintained at an elevated level for a longer period during exogenous infusion than after stimulation by oral glucose. When, in seven volunteers, a lower dose (0.15 pmol/kg.min) of GLP-1 was infused during isoglycemic glucose infusion experiments only for the duration of elevated plasma levels in the oral glucose challenges (0-30 min), a significant, but transient, increment in insulin and C-peptide concentrations was observed, which was equivalent to 26 +/- 10% of the estimated incretin effect. Therefore, in conclusion, circulating GIP seems to make a major contribution to the incretin effect after oral glucose, and GLP-1 appears to mediate a smaller proportion. GIP and GLP-1 can interact in an additive manner in normal man.
Administration, Oral↗
[Diagnostic and therapeutic problems in Lamblia infections].
A 28-year-old woman complained of chronic diarrhoea of about one year's duration, made worse by taking food. As a lactose tolerance test showed evidence of severe intolerance she was given a lactose-free diet, but this brought no improvement. Duodenal biopsy showed villous atrophy, and in the duodenal juice there were numerous flagellated lamblia. After a single oral dose of 2 g tinidazole the diarrhoea stopped, the lamblia disappeared, and the lactose intolerance and villous atrophy cleared up. Lamblia were also detected in the duodenal juice of a 50-year-old woman, but her infection was much more difficult to treat. Tinidazole (single dose of 2 g), metronidazole (800 mg twice daily for 6 days), ornidazole orally 500 mg twice daily for 10 days and ornidazole intravenously 500 mg twice daily for four days all proved ineffective. However, after a 5-day course of epsilon-9-aminacridine (100 mg three times daily by mouth) the diarrhoea ceased and both vegetative forms and lamblia cysts disappeared. These cases emphasize that lambliasis should be considered as a possible cause of severe chronic diarrhoea even when there is no history of travel abroad and when the symptoms are atypical. Conventional chemotherapeutic agents may be ineffective.
Adult↗
Characterization of the Syrian hamster c-Ha-ras gene and intron-D-exon transcript.
The coding sequences as well as 5'- and 3'-flanking sequences of the Syrian hamster c-Ha-ras gene were deduced from cDNA clones derived from embryo fibroblast cell lines. Sequences of introns B, C, and D were obtained from genomic DNA after amplification by the polymerase chain reaction. Sequence comparisons with rat, mouse, and human c-Ha-ras genes revealed a high degree of homology. One of 12 cDNA clones contained intron-D-exon (IDX) sequences due to alternative splicing that would encode a p19 Ha-ras gene product. Conservation between species suggests a functional role for the IDX, possibly as a negative control of p21 Ha-ras expression.
Amino Acid Sequence↗
Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-1-diabetic patients after successful combined pancreas and kidney transplantation.
The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P = 0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and - to a lesser degree - also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P = 0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P = 0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗