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S Graf

Publications and source records attributed to S Graf.

At least 55 records · Page 3Linked to original sources
PubMed1997

Transforming growth factor-beta 3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma.

BACKGROUND: We investigated the role of the transforming growth factor beta (TGF-beta) family in the neoplastic progression of the human prostate. METHODS: Expression of TGF-beta mRNA was measured by Northern blot analysis of tissue extracts, and TGF-beta protein by immunohistochemical analysis of tissue sections. Proliferating cells were detected by their expression of Ki-67 antigen. RESULTS: The level of TGF-beta 1 mRNA was equal among normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma. TGF-beta 2 mRNA was not detectable, and TGF-beta 3 mRNA was expressed 20-fold lesion in carcinoma compared to BPH and normal prostate. TGF-beta 1 protein was expressed in the stromal cells in all three tissues and TGF-beta 3 protein in the basal layer of epithelial cells, but not in carcinoma. Proliferating epithelial cells fail to express TGF-beta 3. CONCLUSIONS: TGF-beta 1 and TGF-beta 3 are independently regulated, and carcinoma of the prostate is characterized by the loss of basal epithelial cells expressing TGF-beta 3.

Adult↗
PubMed1997

5-HT-induced colonic contractions: enteric locus of action and receptor subtypes.

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.

Animals↗
PubMed1997

MRI of inner ear and facial nerve pathology using 3D MP-RAGE and 3D CISS sequences.

The aim of this study was to evaluate 3D CISS, unenhanced 3D MP-RAGE and contrast enhanced 3D MP-RAGE for the diagnosis of neoplastic, vascular and inflammatory lesions of the cerebellopontine angle, the inner auditory canal, the labyrinth and the facial nerve 42 MR examinations were performed on a total of 38 patients (25 males, 13 females; aged 1-77 years, mean age 43 +/- 20 years) using a 1.5 T MR unit. A T2* weighted 3D CISS sequence (TR 14.65 ms, TE 21 ms, flip angle 65 degrees, voxel size 0.7 x 0.7 x 0.7 mm3) and a T1 weighted 3D MP-RAGE sequence (TR 12.5 ms, TE 5 ms, T1 300 ms, flip angle 15 degrees, voxel size 1.0 x 0.9 x 0.9 mm3) with and without contrast medium (gadolinium-DTPA, 0.1 mmol kg-1 body weight) were used. Results of contrast enhanced 3D MP-RAGE-pathological enhancement was found in the following lesions: schwannomas of the cerebellopontine angle (CPA) and the internal auditory canal (IAC), 4; schwannomas of the IAC, 7 and labyrinthine tumours, 3; posterior fossa lymphoma, 1; meatal meningioma, 1; acute labyrinthitis, 15 and neuritis of the seventh cranial nerve, 10. Results of 3D CISS-filling defects were found with the following lesions: schwannomas of the CPA, the IAC or labyrinth, 14; lymphoma, 1; meningioma, 1; labyrinthine fibrosis, 13 and scar in the IAC, 4. These results suggest that unenhanced and contrast enhanced 3D MP-RAGE and 3D CISS are complementary MR imaging modalities. T1 weighted 3D MP-RAGE is preferred to T1 weighted 2D (turbo) spin echo sequences because of the multiplanar reconstruction possibilities of 3D sequences, which are very useful in the case of the inner ear and facial nerve.

Acute Disease↗
PubMed1996

Assessment of myocardial injury by serum tumour necrosis factor alpha measurements in acute myocardial infarction.

Clinical and experimental data have shown that after acute myocardial infarction there is a significant release of tumour necrosis factor alpha. Therefore, an attempt was made to correlate changes in serum tumour necrosis factor alpha concentrations with indices of infarct extent in patients with acute myocardial infarction. In 50 patients with acute myocardial infarction, blood samples for evaluation of tumour necrosis factor alpha and alpha-hydroxybutyrate-dehydrogenase were collected every 6 h until 120 h after admission. Infarct extent was estimated by clinical parameters such as the occurrence of heart failure and rhythm disturbances, by enzymatic methods such as cumulative release of alpha-hydroxybutyrate-dehydrogenase and imaging techniques, by late resting single photon emission tomography--201 thallium scintigraphy--using an extent score and by echocardiography using a wall motion index. The maximum change in serum tumour necrosis factor alpha after infarction (delta TNF) was calculated by subtracting tumour necrosis factor alpha concentration on admission from peak tumour necrosis factor alpha concentration. The average peak tumour necrosis factor alpha level was observed 84 h after admission (median: 12 pg.ml-1). Between the 72nd and the 96th h no significant changes in tumour necrosis factor alpha values were observed. Analysis of the data showed that larger delta (TNF) values were found to be associated significantly with signs of heart failure (P = 0.003), the presence of rhythm disturbances (P = 0.001), increased enzymatic infarct extent indicated by cumulative release of alpha-hydroxybutyrate-dehydrogenase (r = 0.74; P < 0.001), large myocardial perfusion defects measured with 201 thallium scintigraphy (r = 0.80; P < 0.001), and a considerable number of left ventricular wall motion abnormalities (r = 0.57; P < 0.001). In conclusion, delta (TNF) is a reliable method of assessing damage severity in the myocardium after acute myocardial infarction. As only two blood samples are necessary within 84 h, the method may be one of the more convenient for the assessment of infarct size in clinical practice.

Adult↗
PubMed1996

5-HT-induced jejunal motor activity: enteric locus of action and receptor subtypes.

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and receptor subtypes involved in the regulation of jejunal contractions were investigated by close intra-arterial infusions in conscious dogs. Close intra-arterial infusions of 5-HT in short segments of the jejunum stimulated phasic contractions that were blocked completely by atropine, partially by tetrodotoxin, and not affected by hexamethonium. This response was also blocked significantly by 5-HT2A and 5-HT2C receptor antagonists but was not affected by 5-HT1A/5-HT1B, 5-HT3, and 5-HT4 receptor antagonists. Spontaneous phase III contractions were inhibited significantly by 5-HT2A and 5-HT2C receptor antagonists, not affected by 5-HT1A/5-HT1B and 5-HT3 receptor antagonists, and enhanced by 5-HT4 receptor antagonists. Repeated close intra-arterial infusions of 5-HT over several days stimulated giant migrating contractions. We conclude that in the conscious state, 5-HT acts on 5-HT2A and 5-HT2C receptors located on postsynaptic cholinergic neurons in the canine jejunum to stimulate phasic contractions and phase III activity. The 5-HT4 receptors in the canine small intestine may be localized on nonadrenergic, noncholinergic inhibitory neurons; these receptors suppress the amplitude and duration of phase III activity.

Animals↗
PubMed1994

Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A.

Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an i.v. bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 x 150 micrograms rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1-5) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respectively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment days 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-peptide (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control levels (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by approximately 65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.

Adolescent↗
PubMed1994

[The clinical value of plasma fibronectin in pregnancy].

We have measured plasmatic fibronectin in 23 normotensive pregnant women during pregnancy (overall 161 values). On the average 6 samples from every woman have been taken. Plasmatic fibronectin rose continuously from 313 +/- 76 mg/l in the first trimester to 416 +/- 194 mg/l in the third trimester. Normal pregnant women (n = 173, 358 +/- 140 mg/l) were compared with pregnant patients with preeclampsia (n = 37), woman with chronic hypertension in pregnancy (n = 25) and normotensive pregnant patients with intrauterine growth retardation (IUGR, n = 5). In the group with chronic hypertension (466 +/- 119 mg/l) there was no significant difference to the normal group, but we found a significant (p < 0.01) different value of fibronectin (748 +/- 195 mg/l) in the group of patients with preeclampsia. A tendency to higher fibronectin values was also noticed in the group with IUGR (739 +/- 212 mg/l). Because of the low number of patients this difference was not statistically significant. We conclude, that plasmatic fibronectin is an important, but not absolutely specific screening parameter for estimation of the endothelial injury in hypertensive disorders of pregnancy. We believe, that fibronectin is one the best parameters to forecast a preeclampsia.

Adult↗
PubMed1993

Prevalence and long-term outcome of glomerulonephritis in renal allografts.

We report long-term results over 10 years in patients developing glomerulonephritis after renal transplantation. The prevalence rate of glomerulonephritis was 6.2% in 785 renal transplants involving 697 patients with end-stage renal disease. This rate was 14% in patients undergoing biopsy of their grafts because of malfunction. The rate was 15% in patients diagnosed as having glomerulonephritis of any cause prior to transplantation. Membranous, focal sclerosing, and IgA glomerulonephritis were the most common histologic diagnoses. Documented histologic recurrence occurred in only 1% of patients with poor, biopsy-proven glomerulonephritis of their native kidneys. Patients with focal sclerosing glomerulonephritis had the greatest risk from recurrence. De novo glomerulonephritis was most likely to be membranous in character. The graft survival rate of patients with glomerulonephritis was not distinguishable from that of patients showing rejection; both were 45% at 60 months and 33% versus 11%, respectively, at 120 months (P = NS); the graft survival rate in patients without rejection was 76% at 120 months. Thus, glomerulonephritis is responsible for approximately 14% of renal graft malfunction. Glomerulonephritis has a prognosis similar to chronic rejection. Finally, glomerulonephritis as specific histologic recurrence is unusual. Patients with glomerulonephritis should not be discouraged from undergoing transplantation because of putative risks related to recurrence.

Adolescent↗
PubMed1993

Changing trends in the treatment of asthma in a tertiary Canadian pediatric hospital.

During the last few years there has been a major change in the perception of childhood asthma management, with more focus on the anti-inflammatory aspects of therapy, the use of inhaled ipratroprium bromide, and decreased home usage of theophylline. Our clinical impression that the management of asthma at our institution has altered in response to these trends prompted us to review our experience with childhood asthma. A random sample of approximately 70 cases was reviewed from admissions to The Hospital for Sick Children during the first 6 months of 1987 and 1990. There was a major reduction in theophylline usage in 1990 accompanied by increased use of ipratroprium and oral corticosteroids. Significantly fewer cases of potentially toxic theophylline serum levels were observed in 1990, suggesting increased awareness of the this drug's narrow therapeutic margin of safety. In 1990, patients tended to be pyrexial and were treated with antibiotics more often. They were also younger, which may explain the higher pulse and respiratory rates observed. Despite these trends toward younger, sicker patients being admitted to the hospital, the length of stay did not increase, and similar numbers needed intensive care. This suggests that the shift in therapeutic modality did not affect hospitalized asthmatic children adversely.

Asthma↗
PubMed1992

Circadian rhythm and pulsatility of parathyroid hormone secretion in man.

OBJECTIVE: We wished to investigate the circadian rhythm and pulsatility of parathyroid hormone (PTH) secretion in man, as conflicting results have been published. DESIGN AND PATIENTS: To investigate the circadian rhythm during daytime, we sampled (a) peripheral blood at hourly intervals in 12 healthy young men from 0900 h until 1700 h. For observation of pulsatility, we sampled (b) peripheral blood at 1-minute intervals for 1 hour in three healthy men and three healthy women (mean 27.7 years, range 21-56 years) and (c) at 1-minute intervals for 30 minutes in 21 patients with surgically confirmed primary hyperparathyroidism (pHPT). MEASUREMENTS: The serum levels of intact PTH were measured by two-site immunoradiometric assay and special care was taken to reduce intra-assay variability, especially at the normal PTH concentration. In series (a), ionized calcium, total calcium and phosphate were also determined. RESULTS: A circadian rhythm during daytime was found for intact PTH in healthy men and women with a nadir at 0930 h and a peak in the afternoon. Ionized calcium and total calcium (protein-adjusted) decreased and phosphate increased in the afternoon. These changes were all statistically significant (P < 0.02). Pulsatility of PTH: Statistical cluster analysis of the data showed no pulsatility either in healthy persons or in patients with primary hyperparathyroidism. In two healthy women and one healthy man slight changes of longer duration were discovered, but no complete pulses. In five patients with primary hyperparathyroidism, larger differences between the highest and lowest concentrations of intact PTH were found, but no complete pulses. CONCLUSIONS: Our data show a significant circadian rhythm during daytime of intact PTH and only minor changes from minute to minute. The alterations in PTH-levels occurred at longer time intervals in healthy persons. In some patients with primary hyperparathyroidism, decreases of PTH-levels were found. The circadian rhythm of PTH may be due to slight changes in calcium or phosphate concentration.

Adult↗
PubMed1992

Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion.

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.

Adult↗
PubMed1992

[Age- and sex-specific tooth and jaw measurements and their relation in the 1st mixed dentition phase--a longitudinal study on Jena children at the age of 7 1/2 to 8 1/2 years].

In a longitudinal study consisting of three single examinations dental findings of 89 individuals (40 boys and 49 girls) were recorded. The aim of the study was to check up the process of dental growth and development of 7.6- to 8.6-year-old children. Age- and sex-specific differences could be established in the three occlusal dimensions by means of clinical findings and 3-d-analysis of the plaster casts. The rate of DMF teeth was remarkably low in girls and boys; the presence of malocclusions was surprisingly high.

Age Factors↗
PubMed1992

[Clinical aspects, diagnosis and surgical therapy of persistent primary hyperparathyroidism].

Between January 1991 and September 1991 424 patients were operated on for hyperparathyroidism (HPT) at the Department of Surgery, University of Heidelberg. In 8.5% of cases a persistent HPT was present. Our own rate of persistence was 5.4%. Ultrasound revealed the pathology in 44.2% while highly selective venous catheterization identified the correct side in 63.4%. 70% of all patients with persistent HPT required one operative revision, the remaining 30% having up to 3 revisions. 27 patients (75%) were operated on successfully. In 12 of these patients an ectopic adenoma was found. The adenoma was not identified intraoperatively in 2 patients (6.9%). One patient sustained permanent damage to the recurrent laryngeal nerve.

Adenoma↗
PubMed1990

Predicting developmental outcome at school age from infant tests of normal, at-risk and retarded infants.

The predictive validity of developmental testing was investigated in term, preterm and retarded children. Verbal, performance and locomotor development were assessed at various ages and individual development curves constructed. Inter-age correlations between development tests at nine to 24 months and intellectual assessment at seven years revealed a strong effect on prediction for age at testing and level of mental performance. Categorisation by level of mental performance demonstrated that at seven years 98.6 per cent of the children with developmental quotients (DQs) greater than 85 at 24 months achieved IQs greater than 85, while 98.7 per cent of the seven- to eight-year-old children with DQs greater than 85 at nine to 24 months achieved IQs greater than 85. The Griffiths language and performance scores and their combination were the strongest predictors of later intellectual functioning. The social score was of moderate significance, while the locomotor score had no predictive value. Analysis of individual development curves revealed that prediction was hampered in some children by factors not detectable by statistical analysis, such as dissociations in development, organic impairment and major life events. Among the prenatal, perinatal and postnatal variables studied, only socio-economic status was of predictive significance; its effect depended on the level of mental performance and was most marked in term children, but it had no effect on retarded children.

Child↗