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Biomedical subjects

H E Richter

Publications and source records attributed to H E Richter.

At least 19 recordsLinked to original sources

The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation.

GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.

Adipocytes↗

Identification of a novel integral plasma membrane protein induced during adipocyte differentiation.

Adipocyte differentiation is co-ordinately regulated by several transcription factors and is accompanied by changes in the expression of a variety of genes. Using mRNA differential display analysis, we have isolated a novel mRNA, DD16, specifically induced during the course of adipocyte differentiation. DD16 mRNAs are present in several tissues, but among the tissues tested, a remarkably higher level of expression was found in white adipose tissue. The DD16 cDNA encoded a polypeptide of 415 amino acids containing a single N-glycosylation site and an N-terminal hydrophobic stretch of 19 amino acids forming a transmembrane segment, indicating that DD16 is a glycosylated membrane-bound protein. Polyclonal antibodies raised against the DD16 peptide detected immunoreactive DD16 in membrane fractions, notably the plasma membrane. Association of DD16 with the plasma membrane was further confirmed by biotinylation studies of cell surface proteins, suggesting that DD16 is an integral plasma membrane protein. Therefore we propose to give DD16 the name APMAP (Adipocyte Plasma Membrane-Associated Protein). Although the biological function of this polypeptide is presently unknown, our data suggest that APMAP may function as a novel protein involved in the cross-talk of mature adipocytes with the environment.

3T3 Cells↗

Predictors of outcome in small cell carcinoma of the cervix--a case series.

OBJECTIVE: The objective of this study was to determine whether clinicopathologic findings or the immunohistochemical presence of molecular markers are predictive of clinical outcome in patients with small cell carcinoma of the cervix (SCCC). METHODS: A retrospective review of cases of carcinoma of the cervix was conducted to identify SCCC. From 1978 to 1999, 16 patients were identified at our institution with the diagnosis of SCCC. Microscopic sections of paraffin-embedded tissue specimens were evaluated for confirmation of diagnosis. Specimens were immunohistochemically stained with antibodies to three neuroendocrine markers: neuron-specific enolase, chromagranin (CGR), and synaptophysin. Specimens were also stained for protein expression of p53, erbB2, proliferating cell nuclear antigen, and c-myc. The relationship between molecular markers and clinical outcome was determined. RESULTS: All 16 cases met the histologic criteria for SCCC. Fourteen of 16 tumors (88%) stained positive for neuroendocrine differentiation. Eleven of 16 patients (69%) died from disease with a median survival of 19 months; there were 3 long-term survivors (greater than 5 years). CGR was positive in 8 (50%) specimens and was found to be highly predictive of death (P = 0.001). Complete loss of p53 protein was seen in 8 patients, 7 of whom died with a median survival of 20 months. CONCLUSION: Immunohistochemistry can be helpful in confirming difficult cases of SCCC. Further studies are necessary to define molecular markers that may be predictive of outcome in patients with SCCC.

Adult↗

Effects of pubovaginal sling procedure on patients with urethral hypermobility and intrinsic sphincteric deficiency: would they do it again?

OBJECTIVE: This study was undertaken to assess the cure rate of stress urinary incontinence, long-term effects on other lower urinary tract symptoms, and quality of life in a cohort of patients who underwent pubovaginal sling procedures for treatment of incontinence related to intrinsic sphincteric deficiency and urethral hypermobility. STUDY DESIGN: This was a retrospective analysis of 57 patients with 90% follow-up who underwent pubovaginal autologous fascial sling procedures for stress urinary incontinence related to urethral hypermobility and intrinsic sphincteric deficiency. Objective postoperative urodynamic evaluation was performed in 34 (60%) of the cases. Telephone interviews to assess quality-of-life parameters were performed in all cases. RESULTS: The mean follow-up period was 42 months and the median follow-up period was 34 months, with a range of 0.5 to 134 months. The age at the time of the sling procedure ranged from 18 to 84 years, with a median parity of 3.0 (range, 0-6). Preoperative body mass index ranged from 19.5 to 39.1 kg/m(2). Five percent of patients had detrusor instability before the operation. Forty-one percent (41%) of the patients who underwent postoperative urodynamic evaluation had voiding dysfunction. The postoperative objective cure rate for stress urinary incontinence was 97%. Of all patients 88% indicated that the sling had improved the quality of life, 84% indicated that the sling relieved the incontinence in the long-term, and 82% would choose to undergo the procedure again. CONCLUSION: Construction of a pubovaginal sling is an effective technique for relief of severe stress urinary incontinence. Voiding dysfunction is a common side effect. Despite this problem, a significant number of patients would elect to undergo the procedure again.

Adolescent↗

Instability of microsatellites in radiation-associated thyroid tumours with short latency periods.

PURPOSE: To determine the instability of microsatellite sequences in post-Chernobyl thyroid tumours from children and young adults, and to ascertain whether they correlated with the age of the patient at the time of the accident and the tumour latency period. MATERIALS AND METHODS: The stability of 26 microsatellite markers was investigated in 122 radiation-associated thyroid tumours (96 children, 26 adults) from Belarus and 39 spontaneous thyroid tumours (adults) from Munich without radiation history. RESULTS: A significant correlation between patient age at the time of the accident and the instability of microsatellite sequences was established. Also, a high instability of microsatellite sequences was found in 28 early thyroid tumours from Belarus with latency periods of 6-8 years, in contrast to a low instability of microsatellites in 94 tumours emerging 9-11 years after the accident. Microsatellite instability in the reference group from Munich proved similar to the early thyroid tumours from Belarus. CONCLUSION: Early, fast-growing and aggressive post-Chernobyl thyroid tumours are characterized by an increase in microsatellite instability.

Adolescent↗

The association of interleukin 6 with clinical and laboratory parameters of acute pelvic inflammatory disease.

OBJECTIVE: We sought (1) to determine whether interleukin 6 levels are increased in plasma and cervical secretions and endometrial tissue obtained from women with a clinical diagnosis of pelvic inflammatory disease, (2) to determine whether interleukin 6 levels in these sample sites reflected the clinical severity of acute infection, and (3) to determine whether interleukin 6 levels in endometrial tissue obtained from these women were higher in the presence of histologic endometritis. STUDY DESIGN: We performed a prospective pilot study on 20 women with a clinical diagnosis of pelvic inflammatory disease (patients) and then compared them with 20 women presenting to the gynecology clinic without pelvic complaints (control subjects). Interleukin 6 levels were measured by enzyme-linked immunologic testing in plasma, cervical secretions, and endometrial biopsy specimens. RESULTS: Cervical interleukin 6 levels were higher in patients than control subjects (median, 317 vs 111 pg/mL; P =.003). Among women with pelvic inflammatory disease, statistically significant positive correlations were noted between the clinical severity score and the erythrocyte sedimentation rate (r = 0.45; P =.04), the clinical severity score and the white blood cell count (r = 0.49; P =.03), the plasma interleukin 6 levels and the erythrocyte sedimentation rate (r = 0.55; P =.02), and the plasma interleukin 6 levels and the white blood cell count (r = 0.54, P =.01). Endometrial tissue interleukin 6 levels were also higher in patients with versus those without histologic endometritis (median, 427 vs 17 pg/mL; P =.004). CONCLUSION: In this pilot study interleukin 6 levels in cervical secretions were significantly higher in women with pelvic inflammatory disease versus those without pelvic inflammatory disease. In women with pelvic inflammatory disease, endometrial tissue samples with histologic evidence of endometritis were observed to have higher levels of interleukin 6. Interleukin 6 may be a useful adjunct to the clinical diagnosis of pelvic inflammatory disease.

Acute Disease↗

Microsatellite instability and loss of heterozygosity in radiation-associated thyroid carcinomas of Belarussian children and adults.

DNA from 129 paired thyroid tumorous and non-tumorous tissue samples of Belarussian children (102 patients; age at surgery </=18 years) and adults (27 patients; age at surgery 19-35 years), who had been exposed to radioactive fallout from the Chernobyl reactor accident in 1986, was examined for microsatellite instability (MSI) and loss of heterozygosity (LOH). Twenty-eight microsatellite markers were chosen because of their vicinity to DNA repair genes or genes involved in tumorigenesis as well as regions of chromosomal breakpoints in thyroid tumours. In 40 patients (31% of 129) we detected a total of 73 alterations, 80% of which were classified as LOH and only 20% as MSI. Amongst these 40 patients we identified a subgroup of 11, mainly young female patients (8.5% of 129), exhibiting alterations in at least two microsatellite markers. For comparison we examined samples from spontaneous thyroid carcinomas without radiation history from 20 adult patients from Munich (mean age at surgery 56 +/- 13 years). None of the tumour samples investigated showed evidence of alterations in the 28 microsatellite markers tested. Taken together our data indicate an increased instability of microsatellite markers in thyroid cancers from Belarussian patients. At present, it is uncertain whether the increased genome instability observed in Belarussian patients is the result of the exposure to radioactive iodine from the Chernobyl reactor accident or due to the young age of the patients.

Adolescent↗

Neurologic disease presenting as chronic pelvic pain.

Neurologic disease as a cause of chronic pelvic pain may be more common than previously reported. We report three cases wherein patients with complaints of pelvic pain were subsequently found to have neurologic disease involving the lumbosacral spine. In all three cases, the presenting features were complaints of cyclic or noncyclic lower abdominal pain attributed to endometriosis, pelvic inflammatory disease, or uterine fibroids. When conventional therapies failed to resolve the pain, magnetic resonance imaging (MRI) of the lumbosacral spine showed a neoplasm in one patient and disk herniation in two patients. Evolving lumbar disk disease or intradural neoplasms in the upper lumbar area can produce symptoms interpreted as pelvic pain. Symptoms consistent with radiculopathy occurred late in the course of each of the three cases reported.

Adult↗

A psychophysical study of discomfort produced by repeated filling of the urinary bladder.

Psychophysical studies were performed in 10 healthy, female volunteers using urinary bladder distension (UBD) as a visceral stimulus. Stimulus methodology was similar to that used clinically for obtaining cystometrograms with a fixed-rate (100 cc/min normal saline) filling of the urinary bladder, occasional pauses and simultaneous measure of bladder pressure using a catheter-transducer assembly. During bladder filling, subjects were asked to report sensations by verbal report and by using an electronic, hand-held, visual-analog-scale device. Sensations evoked by UBD were generally localized to the suprapubic region. UBD produced cardiovascular responses which increased with repeated trials. Sensation intensity increased with repeated UBDs as indicated by global pain ratings. Intravesical pressure and volume correlated with sensation intensity. The volume of distending fluid needed to produce a report of discomfort was highly variable from trial to trial and did not change significantly with repeated UBDs. The intravesical pressure which produced a report of discomfort was less variable and significantly decreased with repeated UBDs. The change in intravesical pressure and volume needed to produce discomfort was inversely correlated with initial intravesical pressure measures. Similar to findings in other organ systems, these findings demonstrate that repeated presentations of a visceral stimulus may lead to an increase in physiological and perceptual responses to pain.

Adult↗

Laparoscopic and psychologic evaluation of women with chronic pelvic pain.

OBJECTIVE: Pelvic pain can account for up to 40 percent of laparoscopies performed by gynecologists. This report compares the psychological profiles and efficacy of laparoscopic surgery at long-term follow-up in a series of laparoscopy-positive and laparoscopy-negative patients with chronic pelvic pain. METHOD: A retrospective chart review was performed on patients diagnosed with chronic pelvic pain combined with postoperative written questionnaires and self-rating scales. These questionnaires were used to assess long-term post laparoscopy follow-up of the physical and psychological status of women with positive findings at laparoscopy compared to those women with negative findings. RESULTS: There were no statistically significant demographic differences between respondents and nonrespondents. In the respondents, no statistically significant differences were noted even with long-term follow-up when comparing responses of the laparoscopy-positive and laparoscopy-negative groups on the above questionnaires. CONCLUSION: Though reporting modest improvement in pelvic pain since laparoscopy, both groups reported a high incidence of anxiety, depression, physical worries, and marital/sexual problems.

Adult↗

[Psychosocial problems in Huntington chorea. 1: Overview, project description. social and illness-related data].

Huntington's Disease, a neuropsychiatric disorder with dominant inheritance and late manifestation is related to multiple psychosocial problems of the affected person, his life partner as well as their children (so-called individuals at risk). During a five years project the authors contacted 131 persons, directly and indirectly involved in problems with H.D. In the first part the authors present after a general survey sociodemographic and clinical data of the project.

Activities of Daily Living↗

[Psychosocial problems in Huntington chorea. 2: Results and experiences from a 5-year project].

The following article is informing about the experiences from a psychosocial project on Huntington's Disease (HD), a neuropsychiatric disorder with dominant inheritance. The project was running from July 1987 to October 1992 and was funded by the Robert-Bosch-Stiftung. During this project the authors contacted 78 involved families (131 persons), they offered psychotherapies, family-therapies, as well as meetings for patients and explored the subject by semi-structured interviews. The results of this project are presented in the following part.

Adaptation, Psychological↗

Expression pattern and partial sequence analysis of a fetal bovine myosin heavy-chain gene.

A fragment of a bovine myosin heavy-chain (MHC) gene approximately 15 kbp in size (designated MHC 67) was isolated from a bovine genomic DNA library. The direction of transcription was determined, and preliminary experiments indicated that the gene was expressed in fetal skeletal muscle. The expression pattern of this gene was, therefore, evaluated in detail using northern blots containing RNA from eleven different bovine muscle and nonmuscle tissues at three developmental ages. A restriction fragment of clone MHC 67 containing the 3' untranslated sequence (which is specific for each MHC gene) was used as a probe. This gene fragment hybridized predominantly to RNA from fetal skeletal muscles and did not hybridize to RNA from either neonatal or adult skeletal muscles (red or white), smooth muscle tissue, or nonmuscle tissue. A 7-kb EcoRI fragment containing both translated and untranslated regions surrounding the 3' end of the gene was subcloned into pBluescript II KS+ and partially sequenced. When these bovine sequences were aligned to that of the human and rat skeletal and cardiac MHC genes, we found that these sequences corresponded to exons 31, 32, and 33, and that they had homology with human perinatal and fetal MHC as high as 90% at the nucleotide level and 97% at the amino acid level. Comparison of the nucleotide sequences of isoform-specific 3' nontranslated regions from bovine, human, and rat genes further verify that the MHC 67 clone encodes the bovine fetal or perinatal MHC isoform.

Amino Acid Sequence↗

[Self-criticism and reconciliation capacity].

With reference to empirical socio-psychological studies conducted by the author himself (on prejudices in connection with AIDS, inquiries into attitudes displayed by German and Russian students) and the results of opinion polls on xenophobia, racism and nationalism, the author demonstrates that reconciliation with oneself and others is proportional to the propensity for self-criticism and the ability to recognize and acknowledge personal guilt. Where, by contrast, self-hatred and self-devaluation prevail, the tendency towards projection and hatred of others will also be dominant.

Defense Mechanisms↗

Characterization and genomic organization of a highly expressed late nodulin gene subfamily in soybeans.

A soybean nodulin cDNA clone (E41) hybrid-selected mRNA for three in vitro translation products with apparent molecular weights of 26 kDa, 25 kDa and 24 kDa. Based on Southern analysis of soybean genomic DNA, combined with mapping and sequencing of genomic clones, we identified four genes that are related to E41, one of which was identified to be the previously characterized N-20 gene. Our data indicate the linkage of three of the genes, of which one is a truncated version and suggest that they originated by gene duplication combined with deletion and conversion. The genes are highly expressed and we postulate that the sequence conservation in the 5' and 3' flanking regions of all four genes, has a functional role in their expression. Hybrid-selected translation products of E41 are not immunoprecipitable with antibody to the soluble fraction of nodules suggesting that they are membrane associated. The N-20 gene, which is a member of this gene subfamily, showed sequence similarity to four previously characterized nodulin genes and a phylogenetic tree is proposed based on the extent of sequence similarity.

Base Sequence↗

Protein metabolism in chicken muscle cell cultures treated with cimaterol.

Primary muscle cell cultures were prepared from the leg muscle of 12-d broiler chicken embryos. The partitioning agent cimaterol (10(-6) to 10(-10) M) was added on d 1 and each day thereafter, and cells were studied after 7 d in culture. Cimaterol had no effect at any level either on the percentage of nuclei within multinucleated myotubes or on the total number of nuclei within myotubes. At 10(-7) M cimaterol, the quantity of the myofibrillar protein fraction was increased by 25.1 +/- 8.0% (P less than .05) and the quantity of myosin heavy chain was increased by 30.9 +/- 4.5% (P less than .05). To understand the basis for the increase in myofibrillar protein, the incorporation rate of [3H]Leu was measured in pulse labeling experiments. The apparent synthesis rate of the soluble protein fraction and the crude myofibrillar fraction was not significantly increased by cimaterol; however, cimaterol levels greater than 10(-8) M caused a 10 to 12% increase (P less than .05) in the incorporation rate of [3H]Leu into myosin heavy chain. The effect of cimaterol on release of [3H]Leu from prelabeled protein also was assessed in pulse-chase experiments; the apparent rate of protein degradation was inhibited by 10 to 15% (P less than .05) at the higher levels of cimaterol. Dot blot analysis indicated that the quantity of myosin heavy chain mRNA was elevated in cimaterol-treated cultures. Thus, the increased quantity of myofibrillar proteins in embryonic broiler muscle cell cultures is the combined result of a stimulation in the rate of protein synthesis and an inhibition in the rate of protein degradation.

Adrenergic beta-Agonists↗

[The significance of psychology in medicine].

It is shown in a retrospective review how the specific political climate twenty years ago helped to establish psychosomatics, psychotherapy and medical psychology as disciplines in their own right. The "reform-minded" trend gave psychotherapy recognition as a treatment method to be acknowledged as cost-refundable under the Federal German health insurance system. Furthermore, it prompted the Federal German government to start an inquiry into the present situation of psychiatry and psychosomatic medicine, whereas research workers at the base developed models of psychosocial working teams and of a renewal of sociopsychiatry. Meanwhile the political "turnabout" in the Federal Republic from a socioliberal to a predominantly conservative line has produced a conservative countercurrent: the medical institutions undergo reinstatement of ancient hierarchies, jobs in the psychosocial sphere are being dramatically axed, psychosomatics is being streamlined as an adapted auxiliary discipline ruled with an iron hand by a dramatically expanding clinical pathology or laboratory medicine and by a concept of "health" that is purely functional. Basing on the case history of a woman suffering from psychogenic sterility the author critically discusses the gap-clearly noticeable although frequently denied-now dividing the individual disciplines and schools of psychological medicine, separating in each case a preferably conformistic branch from a critically engaged one.

Adult↗

Effect of ascorbate on oxygen uptake and growth of Escherichia coli B.

The addition of ascorbate to aerobically growing cultures of Escherichia coli B caused only a short pause in growth and no subsequent change in the rate or extent of growth. The effect of ascorbate on oxygen uptake varied from inhibition in minimal medium to stimulation in rich medium. Cyanide-resistant growth and oxygen uptake were stimulated by ascorbate. Both the rate and extent of anaerobic growth were stimulated in proportion to the amount of ascorbate added when fumarate was the terminal electron acceptor. Ascorbate had no effect on any aspect of anaerobic growth in the absence of a terminal electron acceptor or in the presence of nitrate.

Anaerobiosis↗