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Biomedical subjects

H Schulze

Publications and source records attributed to H Schulze.

At least 55 records · Page 3Linked to original sources
PubMed1999

Suramin treatment in hormone- and chemotherapy-refractory prostate cancer.

OBJECTIVES: Suramin, a polysulfonated naphtylurea with anti-growth factor activity, was used in the treatment of metastatic, hormone- and chemotherapy-refractory prostate cancer. Recent studies have proved the effect of suramin on prostate cancer. METHODS: Between March 1990 and January 1994, 27 patients with metastatic prostate cancer were enrolled in this study. Treatment regimen consisted of a loading phase, allowing patients to reach suramin serum levels between 180 and 250 microg/mL using a suramin dose of 1.4 g/m2 at 3-day intervals. Constant suramin serum levels were maintained by a 0.5 to 1-g/m2 dose every 7 to 10 days. Because previous studies showed suramin to have serious toxicity, compromised organ status was excluded by repeated examinations. RESULTS: Six patients did not complete the suramin loading phase because of side effects and were removed from the study. With an average cumulative suramin dose of 14.2 g, 33% of the assessable patients (7 of 21) experienced a more than 50% reduction of prostate-specific antigen (PSA) and/or alkaline phosphatase (AP) serum levels. Mean survival in these suramin-responsive patients was 495 days. Two of these patients experienced a remarkable reduction of metastases in bone scan examinations. Another 48% of the patients (10 of 21) had essentially unchanged AP and PSA serum levels during suramin treatment, indicating stable disease. Mean survival of these patients was 341 days. In 4 patients undergoing suramin treatment, continuous clinical progression of the disease was observed (mean survival 79 days). Toxicity was less or comparable to prior reported studies; the most common side effects were polyneuropathy, allergic skin rash, and vortex keratopathy. CONCLUSIONS: Suramin has limited, but significant, efficacy even in chemotherapy- and hormone-refractory prostate cancer, without serious toxicity.

Aged↗
PubMed1998

Defective c-Mpl signaling in the syndrome of thrombocytopenia with absent radii.

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital defect with severe hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. To elucidate a possible relationship between thrombocytopenia in TAR and defects in the thrombopoietin (TPO)/c-Mpl system, we examined TPO activity in sera from six patients and in vitro reactivity of the patients' platelets to recombinant human TPO. We found elevated TPO serum levels in all patients, excluding a TPO production defect as a pathomechanism for the thrombocytopenia. In contrast to healthy controls, however, platelets of TAR patients failed to respond to recombinant TPO as measured by testing TPO synergism to suboptimal concentration of platelet activators. Most interestingly, TPO-induced tyrosine phosphorylation of platelet proteins was completely absent (four out of five) or markedly decreased (one out of five). More detailed investigations of the signal cascades of c-Mpl demonstrated the absence of Jak2 phosphorylation after TPO stimulation in a TAR patient's platelets. A defect in the early events of c-Mpl signal transduction might be the reason for impaired megakaryocytopoiesis in TAR syndrome.

Blood Platelets↗
PubMed1998

[High-flow priapism following blunt perineal trauma. Interventional therapy].

A 10-year old boy developed an arteriocavernosal fistula with a permanent penile erection (high-flow priapism) after a blunt perineal trauma. The diagnosis was established by Doppler ultrasound, blood gas analysis and angiography. A conservative treatment attempt with penile cooling and puncture of the cavernosal corpera with blood aspiration and etilefrine instillation failed to resolve the priapism. An embolization of both bulbocavernosal arteries was followed by an immediate detumescence. Normal functional erection was preserved. No recurrence was observed during a follow-up of 6 months.

Accidents, Traffic↗
PubMed1998

Guanidinated protein test meals with higher concentration of soybean trypsin inhibitors increase ileal recoveries of endogenous amino acids in pigs.

The amino acid concentrations of cornstarch-based guanidinated unprocessed (UGM) and autoclaved (AGM) Nutrisoy (defatted soy flour) protein test meals were compared with the respective unguanidinated Nutrisoy diets. Endogenous ileal recoveries and true digestibilities of amino acids were determined in six growing pigs, fitted with a simple T-cannula at the distal ileum, fed the guanidinated protein test meals. The UGM and AGM contained 13.4 (high) and 3.0 (low) g/kg dry matter of soybean trypsin inhibitors (SBTI), respectively. The experiment was a two-period cross-over design with each period lasting 15 d. On d 14 of each period, the pigs were fed the guanidinated test meals followed by 24 h continuous collection of digesta. Concentrations of crude protein and most of the amino acids in the test meals were higher than in the respective diets. Apparent ileal amino acid digestibilities of the test meals did not differ (P > 0.05) from reported values for the respective diets and were higher (P < 0.05) by 22.7 (cysteine) to 61.3 (tyrosine) percentage units for AGM compared with UGM. The ileal recoveries of endogenous amino acids in AGM-fed pigs were lower (P < 0.05) than UGM-fed pigs. Values ranged from -0.10 (arginine) to 0.64 (aspartate + asparagine) and from 0.84 (histidine) to 2.61 (tyrosine) g/kg dry matter intake for AGM- and UGM-fed pigs, respectively. True ileal amino acid digestibilities for AGM were higher (P < 0.05) than UGM with differences ranging from 12.7 (tyrosine) to 38.3 (leucine) percentage units. In conclusion, ileal recoveries of endogenous amino acids were increased in pigs fed guanidinated protein test meals with the higher concentration of SBTI.

Amino Acids↗
PubMed1997

Crystal structure of cytochrome P-450cam complexed with the (1S)-camphor enantiomer.

The crystal structure of cytochrome P-450cam complexed with the enantiomer (1S)-camphor has been solved to 1.8 angstroms resolution and compared with the structure of the (1R)-camphor P-450cam complex. The overall protein structure is the same for both enantiomer complexes. However, the orientation of the substrates in the heme pocket differs. In contrast to (1R)-camphor, the (1S)-enantiomer binds in at least two orientations. The major binding mode of (1S)-camphor resembles the one of the (1R)-enantiomer in that there is a hydrogen bond between Tyr-96 and the quinone group of camphor, and the 10-methyl group points towards the I-helix. The binding differs in that C-5 is not at a position suitable for hydroxylation. In the other orientation (1S)-camphor is not hydrogen bonded, but C-5 is located suitably for hydroxylation.

Camphor↗
PubMed1997

Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin.

The pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndrome. In addition, we found similar expression of the TPO receptor c-Mpl on the surface of platelets from TAR patients (5 of 5) and a similar molecular weight of the receptor as compared with healthy controls (4 of 4). Platelet response to adenosine diphosphate or thrombin receptor agonist peptide SFLLRN (TRAP) was normal in TAR patients. However, in contrast to results with healthy controls we could show absence of in vitro reactivity of platelets from TAR patients to recombinant TPO as measured by testing TPO synergism to adenine diphosphate and TRAP in platelet activation. TPO induced tyrosine phosphorylation of platelet proteins was completely absent (3 of 4) or markedly decreased (1 of 4). Our results indicate that defective megakaryocytopoiesis/thrombocytopoiesis in TAR syndrome is not caused by a defect in TPO production but a lack of response to TPO in the signal transduction pathway of c-Mpl.

Blood Platelets↗
PubMed1997

Mobility of norbornane-type substrates and water accessibility in cytochrome P-450cam.

The behaviour of norbornane-type substrates bound to oxidised cytochrome P-450cam (CYP 101) in 60% (w/w) glycerol-containing phosphate buffer was investigated using electronic absorption spectroscopy. The high-pressure dependence study revealed that the value of the spin-state reaction-volume change decreased from -70 to -22.8 cm3/mol with decreasing high-spin state content from 99 to 63%. Simultaneously, the values for the enthalpy and entropy determined from the low-temperature dependence of the spin-state transition decreased from 73.7 to 24.3 kJ/mol and from 310.4 to 88.9 J/mol K, respectively. Under our experimental conditions the pH-value of the buffer remained at low temperatures and high pressures in the range of pH 7-8, in which no pH-value-induced spin-state conversion occurred. Therefore, the secondary effect of the temperature and pressure-induced pH change can be disregarded as being responsible for the observed spin-state transition effects. Substrate dissociation constants were determined. From the temperature-jump experiments (297 K to 180 K) we found a higher mobility in the active site for the substrates in the sequence (1R)-camphor, (1S)-camphor, camphane, (1R)- and (1S)-camphorquinone, norcamphor, and norbornane. Our findings can be explained by the incomplete fit of the methyl groups of the norbornane-type substrate to the protein, in particular to the I-helix, predominantly determining the substrate mobility and water accessibility to the protein.

Binding Sites↗
PubMed1997

Field-specific responses in the auditory cortex of the unanaesthetized Mongolian gerbil to tones and slow frequency modulations.

Responses of multi-units in the auditory cortex (AC) of unanaesthetized Mongolian gerbils to pure tones and to linearly frequency modulated (FM) sounds were analysed. Three types of responses to pure tones could be clearly distinguished on the basis of spectral tuning properties, response latencies and overall temporal response pattern. In response to FM sweeps these three types discharged in a temporal pattern similar to tone responses. However, for all type-1 units the latencies of some phasic response components shifted systematically as a function of range and/or speed of modulation. Measurements of response latencies to FMs revealed that such responses were evoked whenever the modulation reached a particular instantaneous frequency (Fi). Effective Fi was: (1) independent of modulation range and speed, (2) always reached before the modulation arrived at a local maximum of the frequency response function (FRF) and consequently differed for downward and upward sweeps, and (3) was correlated with the steepest slope of that FRF maximum. The three different types of units were found in discrete and separate fields or regions of the AC. It is concluded that gross temporal response properties are one of the key features distinguishing auditory cortical regions in the Mongolian gerbil.

Acoustic Stimulation↗
PubMed1997

Periodicity coding in the primary auditory cortex of the Mongolian gerbil (Meriones unguiculatus): two different coding strategies for pitch and rhythm?

Periodic envelope or amplitude modulations (AM) with periodicities up to several thousand Hertz are characteristic for many natural sounds. Throughout the auditory pathway, signal periodicity is evident in neuronal discharges phase-locked to the envelope. In contrast to lower levels of the auditory pathway, cortical neurons do not phase-lock to periodicities above about 100 Hz. Therefore, we investigated alternative coding strategies for high envelope periodicities at the cortical level. Neuronal responses in the primary auditory cortex (AI) of gerbils to tones and AM were analysed. Two groups of stimuli were tested: (1) AM with a carrier frequency set to the unit's best frequency evoked phase-locked responses which were confined to low modulation frequencies (fms) up to about 100 Hz, and (2) AM with a spectrum completely outside the unit's frequency-response range evoked completely different responses that never showed phase-locking but a rate-tuning to high fms (50 to about 3000 Hz). In contrast to the phase-locked responses, the best fms determined from these latter responses appeared to be topographically distributed, reflecting a periodotopic organization in the AI. Implications of these results for the cortical representation of the perceptual qualities rhythm, roughness and pitch are discussed.

Acoustic Stimulation↗
PubMed1997

Frequency and periodicity are represented in orthogonal maps in the human auditory cortex: evidence from magnetoencephalography.

Timbre and pitch are two independent perceptual qualities of sounds closely related to the spectral envelope and to the fundamental frequency of periodic temporal envelope fluctuations, respectively. To a first approximation, the spectral and temporal tuning properties of neurons in the auditory midbrain of various animals are independent, with layouts of these tuning properties in approximately orthogonal tonotopic and periodotopic maps. For the first time we demonstrate by means of magnetoencephalography a periodotopic organization of the human auditory cortex and analyse its spatial relationship to the tonotopic organization by using a range of stimuli with different temporal envelope fluctuations and spectra and a magnetometer providing high spatial resolution. We demonstrate an orthogonal arrangement of tonotopic and periodotopic gradients. Our results are in line with the organization of such maps in animals and closely match the perceptual orthogonality of timbre and pitch in humans.

Acoustic Stimulation↗
PubMed1997

Listeriosis in p47(phox-/-) and TRp55-/- mice: protection despite absence of ROI and susceptibility despite presence of RNI.

The significance of host defense mechanisms in primary listeriosis in vivo is incompletely understood. Here, we show that tumor necrosis factor receptor p55-/- (TRp55-/-) mice are susceptible to Listeria monocytogenes infection in the presence of leukocyte recruitment, inflammatory cytokine production (including IFNgamma), nitric oxide synthesis, and oxidative burst formation. Mice deficient for oxidative burst (p47[phox-/-] mice) are relatively resistant to listeriosis. Despite activation of these antibacterial effector systems, TRp55-/- phagocytes in vivo are incapable of confining and eradicating L. monocytogenes inside phagolysosomes. Bone marrow chimeras reveal that for eradication of L. monocytogenes, TRp55 is crucially required only on cells from hematopoietic origin. Unexpectedly, prior to death, exocrine pancreatic cells undergo apoptosis in TRp55-/- mice. Collectively, these data demonstrate that in vivo, TRp55 initiates a protective, listericidal mechanism in phagocytes that differs from nitric oxide production and oxidative burst formation and that uncontrolled listeriosis results in necrotizing pancreatitis in TRp55-/- mice.

Animals↗
PubMed1997

Using the World Wide Web--a new approach to risk identification of diabetes mellitus.

Diabetes mellitus is a major health problem with a rising tendency world-wide. A new strategy for risk evaluation and data collection of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) using the World Wide Web (WWW) is presented. An easy-to-handle questionnaire on typical risk factors was converted into an interactive WWW document. The Internet provides the suitable platform for the net-based distribution of the questionnaire form as well as the computer-assisted entering and interpretation of the data (http:(/)/www.uni-leipzig.de/-diabetes). The analysis program, installed on our WWW server, interprets the information and sends the assessment on-line back to the inquiring user PC. The data are also collected anonymously in a database for epidemiological studies. In the test period, 744 world-wide accesses were registered: 433 men, mean age 39.8 +/- 14.4 years (range 10-83) and 311 women, mean age 36.7 +/- 12.7 years (range 11-77). An increased risk for undiagnosed diabetes was identified to 43.6%. The risk profile of male and female users showed no significant gender-related differences. Using the WWW technology can support early detection and adequate treatment of undiagnosed diabetes. This innovative strategy to screen for a high risk profile is an useful, cost-effective and up-to-date tool for broad community health education and epidemiological studies world-wide.

Adolescent↗
PubMed1997

Cell kinetic in epithelium and stroma of benign prostatic hyperplasia.

The induction of benign prostatic hyperplasia (BPH) from normal prostate is obviously associated with a distinct increase in epithelial and stromal proliferation. We have shown previously that the further increase of BPH volume in aging men is not associated with a further increase in proliferation. We studied whether an imbalance between programmed cell death (apoptosis) and cell proliferation may explain continuing growth in aging men. In prostates of 17 men with BPH removed by open prostatectomy proliferating cells were localized immunohistochemically with the Ki-67 antibody. Apoptotic cells were detected with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. Proliferation and apoptotic index was calculated with a computer assisted image analysis system. Mean proliferation index +/- standard deviation in epithelium (0.142 +/- 0.097) and stroma (0.121 +/- 0.082) was nearly identical. Mean apoptotic index in epithelium (0.172 +/- 0.156) was negligibly higher than the corresponding proliferation index. In stroma, however, no apoptotic cells were detectable. Proliferation index and apoptotic index in epithelium and proliferation index in stroma showed no correlation to patient age or prostate volume. In the epithelium of BPH, obviously the cell kinetic is balanced. On the other hand, our results indicate stromal growth due to cell proliferation in the absence of cell death. This may explain the continuous increase of BPH volume in aging men.

Adult↗
PubMed1997

[Aspergillus fumigatus and Chaetomium homopilatum in a leukemic patient. Pathogenic significance of Chaetomium species].

From the tracheal secretion of a leukaemic patient Aspergillus fumigatus and Chaetomium homopilatum was isolated. Radiographically (HR-CT) an invasive pulmonary mycosis was diagnosed from which the patient died. As an autopsy was not performed, the role of the isolated fungi could not be clarified safely. Aspergillus fumigatus is supposed to have been responsible for the invasive mycosis. The etiopathological significance of Ch. homopilatum remained unclear. The isolation of Ch. homopilatum was a reason for reviewing the genus Chaetomium. In the literature 18 reported cases of infections by Chaetomium sp. were found. Ch. globosum was the most prevalent species and caused mostly onychomycosis. Ch. strumarium and Ch. atrobrunneum caused brain infections. The predisposing factor in case of onychomycosis and cutaneous lesions was a trauma, and the systemic mycoses were a consequence of leukaemia, renal transplantation, intravenous drug use or renal failure. The reported cases show, that Chaetomium sp. may cause infections, if predisposing factors are present. Therefore the isolation of Chaetomium sp. in clinical specimen should not regarded as a contamination, and the possible etiopathological significance should be clarified.

Adult↗
PubMed1997

Glans hyperemia after penile revascularization: a late complication following alpha-1-receptor blockade for benign prostatic hyperplasia.

Surgical revascularization of the penile vessels is one treatment choice for patients with vasculogenic impotence. Hyperemia of the glans is a rare but severe complication which usually occurs early. We report a patient who developed this complication more than 3.5 years after surgery following onset of medical treatment of benign prostatic hyperplasia with a vasodilating alpha 1-receptor blocker.

Adrenergic alpha-Antagonists↗
PubMed1997

N-Acetyltransferase 2 (NAT2) and Glutathione S-Transferase µ (GSTM1) in Bladder-cancer Patients in a Highly Industrialized Area.

The study was designed to assess occupational and non-occupational risk factors in patients with urothelial carcinomas in an area of former coal, iron, and steel industries, with special regard to the impacts of polymorphic enzymes involved in the metabolism of aromatic amines (N-acetyltransferase 2, NAT2) and of polycyclic aromatic hydrocarbons (glutathione S-transferase µ, GSTM1). Inpatients with bladder cancer (n = 179) were interviewed for occupations ever engaged in for more than six months, and for bladder cancer risk factors in general. NAT2 was phenotyped by high-pressure liquid chromatography of caffeine metabolites in urine. The NAT2 status was additionally evaluated by genotyping 88 of these patients. Eighty-nine patients were genotyped for GSTM1. Of the 179 bladder-cancer patients, 115 (64%) were slow acetylators. In 70% of the subgroup of 89 patients, GSTM1 was negative, suggesting an impact of polycyclic aromatic hydrocarbons (PAHs) in bladder-cancer carcinogenesis in the general population in this area. Contrary to an ordinary distribution of the acetylator status in underground coal miners (18 slow acetylators out of 32), GSTM1 was negative in 16 of 19 of these coal miners. Five of six coke-oven workers were slow acetylators; GSTM1 was negative in all four genotyped coke-oven workers. Twelve of 17 patients formerly exposed to colorants were slow acetylators. Distributions of NAT2 (59% slow acetylators) and GSTM1 (54% GSTM1 negative) were normal in businessmen and administrative officers among the occupationally non-exposed bladder-cancer patients. The results are consistent with the view that a slow-acetylator status and lack of the GSTM1 gene are individual risk factors for bladder cancer in persons occupationally exposed to aromatic amines and PAHs. Aromatic amines may be connected with induction of bladder cancer in persons who have been in contact with azo dyes and in coke-oven workers. PAHs may also contribute to elevated bladder-cancer risks in coke-oven workers and in underground coal miners.

Journal Article↗
PubMed1997

Apparent ileal digestibilities of amino acids in newly weaned pigs fed diets with protease-treated soybean meal.

Apparent ileal digestibilities of amino acids were determined in pigs fed cornstarch-based diets with untreated or protease-treated soybean meal as the protein source. Sixteen pigs were fitted with a modified post valve T-cecum cannula on d 14, 15, and 16 after birth and then returned to their sows until d 20 when they were weaned. Twelve of the pigs were selected for the study, which was conducted according to a two-period balanced change-over design. Treatments consisted of soybean meal that was 1) untreated (SBM), 2) processed by incubation (1:2 wt/vol distilled water adjusted to pH 4.5, for 16 h at 50 degrees C; CI-SBM), 3) sprayed with protease (supplied at 1 microL/g of soybean meal; PS-SBM), and 4) processed by incubation, as for CI-SBM, with protease in the water at the rate of 1 microL/g of soybean meal (PI-SBM). Each period consisted of 5 d of adaptation to diets followed by three 8-h collection periods (total of 24 h) that alternated with 8-h periods in which digesta were not collected. Apparent CP digestibilities were similar (P > .05) at 70.4, 72.4, 65.2, and 70.3% for the SBM, CI-SBM, PS-SBM, and PI-SBM diets, respectively. Corresponding amino acid digestibilities were also similar (P > .05), ranging from 62.5, 67.5, 57.9, and 65.0% for alanine to 83.5, 83.4, 78.7, and 84.7% for arginine. Apparent digestibilities were less (P < .05) for Period 1 (on d 7 after weaning) than for Period 2 (on d 16 after weaning). In conclusion, protease treatment of soybean meal had no effect on ileal digestibilities of CP and amino acids in newly weaned pigs.

Administration, Topical↗