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Biomedical subjects

H Weiss

Publications and source records attributed to H Weiss.

At least 109 records · Page 6Linked to original sources

Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma.

The products of bcl-2 and p53 genes are involved in the regulation of apoptosis and proliferation and have been associated with prognosis in several malignancies, including colorectal adenocarcinoma. Although 2 European studies have reported a prognostic significance of Bcl-2 expression in colorectal adenocarcinomas, a study from the United States did not observe such an association. Therefore, we used immunohistochemistry to evaluate the prognostic significance of Bcl-2 expression, p53 nuclear accumulation and their concomitant expression in 134 US patients with colorectal adenocarcinoma. Antigen retrieval was required for adequate detection of Bcl-2 expression. Fifty percent of the colorectal tumors were classified as expressing Bcl-2, and Bcl-2 expression was associated with longer patient survival. Antigen retrieval was not necessary for detecting nuclear accumulation of p53 by immunohistochemistry. Nuclear accumulation of p53 was detected in 44% of colorectal adenocarcinomas and was associated with decreased patient survival. Tumors that did not express detectable levels of Bcl-2 but exhibited nuclear accumulation of p53 were associated with the shortest patient survival (log rank, p = 0.001). Multivariate Cox regression analysis demonstrated that Bcl-2 expression (p = 0.018), p53 nuclear accumulation (p = 0.024) and regional lymph-node metastasis (p = 0.005) were independent prognostic factors. Although a trend toward an inverse correlation between Bcl-2 and p53 expression was observed, the prognostic value of Bcl-2 expression was independent of p53 status. Thus, assessment of both Bcl-2 and p53 status may be valuable in predicting the prognosis of patients with colorectal adenocarcinomas.

Aged↗

Mitochondrial fatty acid synthesis: a relic of endosymbiontic origin and a specialized means for respiration.

Genes that encode mitochondrial homologues to the bacterial enzymes of fatty acid synthesis were found in various eukaryotic species. Inactivation of these genes leads to a disturbed mitochondrial respiration and an increase in mitochondrial lysophospholipids. We postulate that there is a mitochondrial biosynthetic system providing fatty acids for phospholipid repair. The mitochondrial acyl carrier protein may also play another role, supporting the formation of the respiratory NADH:ubiquinone oxidoreductase.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Three-dimensional structure of NADH-dehydrogenase from Neurospora crassa by electron microscopy and conical tilt reconstruction.

NADH-dehydrogenase (Complex I) is the first complex of the mitochondrial respiratory chain. It is an amphipatic molecule located in the inner mitochondrial membrane and is composed of at least 35 unique subunits encoded by both mitochondrial and nuclear DNA. The whole complex was isolated in detergent from the fungus Neurospora crassa. It is very stable in its isolated form and was analysed as such by electron microscopy. Its mass, determined by dark-field scanning electron microscopy was estimated as 1.12 MDa. The complex was imaged by transmission electron microscopy, by negative staining and by cryo-electron microscopy. A three-dimensional model, with a resolution estimated at 35 A, was calculated from images of negatively stained complexes by the random conical tilt reconstruction technique. This model confirms the general L-shape of the molecule, with arms of equal length and corroborates the hypothesis of a subdivision of the whole complex into three functional domains. Immuno-labelling of the 49 kDA subunit of the peripheral arm allowed its localization within the complex. This is a first step in the subunit mapping of Complex I and the understanding of its activity.

Animals↗

Two genes of the putative mitochondrial fatty acid synthase in the genome of Saccharomyces cerevisiae.

In order to find further genes of the mitochondrial fatty acid synthase, we searched the genome of Saccharomyces cerevisiae for sequences that are homologous to conserved regions of bacterial fatty acid synthase genes. We found the gene products of ORF YKL055c (EMBL Accession No. X75781) and of YOR221C (EMBL Accession No. X92441) to be homologous to bacterial 3-oxoacyl-(acyl carrier protein) reductases and to malonyl-CoA:ACP-transferases, respectively. We disrupted these two genes which in both cases led to a respiratory deficient phenotype, as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase. We propose to call the above mentioned genes OAR1 [3-oxo-acyl-(acyl carrier protein) reductase] and MCT1 (malonyl-CoA:ACP transferase). They are presumed to be part of a type-II mitochondrial fatty acid synthase, a relic of the endosymbiontic origin of mitochondria, delivering substrates for phospholipid re-modelling and/or repair.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗

Efficacy of carteolol hydrochloride 1% vs timolol maleate 0.5% in patients with increased intraocular pressure. Nocturnal Investigation of Glaucoma Hemodynamics Trial Study Group.

PURPOSE: To evaluate the ocular hypotensive effect and safety of carteolol hydrochloride 1% vs timolol maleate 0.5%. METHODS: One hundred seventy-six patients with ocular hypertension or primary open-angle glaucoma were randomly assigned to receive either carteolol 1% twice a day or timolol maleate 0.5% solution twice a day in a randomized, double-masked, multicenter, parallel-group, active-control comparison trial during a 3-month period. RESULTS: After 12 weeks, carteolol 1% reduced the mean +/- SE intraocular pressure from 25.0 +/- 0.3 to 19.5 +/- 0.3 mm Hg; timolol maleate 0.5% reduced the mean intraocular pressure from 25.2 +/- 0.3 to 19.6 +/- 0.3 mm Hg. The mean difference in trough intraocular pressure between carteolol and timolol maleate of -0.14 mm Hg was not significantly (P = .745) different (95% confidence limits, -0.97 to 0.70 mm Hg). Trough pulse and blood pressure also showed no consistent statistically significant differences between groups. The 2-hour postdose pulse, however, demonstrated a greater decrease in the timolol maleate than in the carteolol group (P < .001). Systemic and ocular signs and symptoms were similar between the groups except that the number of treatment-emergent reports of bradycardia was greater in the timolol maleate group (P = .039), and the carteolol group reported fewer ocular symptoms than the timolol maleate group did (P < .01). CONCLUSIONS: Both carteolol 1% and timolol maleate 0.5% are highly effective in lowering intraocular pressure when measured at the end of the dosing interval. Carteolol 1% demonstrates an ocular hypotensive effect and safety profile similar to those of timolol maleate 0.5% solution.

Adolescent↗

[The clientel of a psychotherapeutic polyclinic in the light of a documentation base].

A documentation system for use during the diagnostical process with psychotherapy outpatients is outlined, and sociodemographic, medical and psychosocial data of newly admitted patients of a university psychotherapy outpatient department are presented. The population structure is described on the basis of data collected during the first 18 months of the implementation of the assessment system. Data are compared with those of other psychotherapeutical institutions that differ with regard to setting (outpatient vs. inpatient), health care sector (acute care vs rehabilitation) and geographic region. Sociodemographic and medical data are given. Patients' mean age is 33.5 years. Two-thirds of the patients are female. The majority is single and has higher formal education. Slightly more than half of the patients are working. Modes of admittance, somatic and psychological complaints and aspects of illness behaviour are described. Pertaining to diagnostical classification, affective disorders (34%), somatoform disorders (15%) and anxiety disorders (11%) are most frequent. Mean duration of symptoms is 6 years. However, only few patients had prior psychological treatment. Treatments most frequently selected at the time of assessment were psychodynamic psychotherapy (41%), behavioural therapy (24%), and group therapy (10%). When comparing the study population with those of other institutions, differences showed up especially in contrast to rehabilitation clinics, where older, male, and working persons as well as those with somatoform disorders and longer durations of illness are more frequent.

Adult↗

Significance of apoptosis in the process of tumorigenesis in colorectal mucosa and adenomas in FAP patients.

The relation between proliferation and apoptosis was studied in colorectal mucosal biopsies (N = 41), tubular adenomas (TA) (N = 104) and tubulovillous adenomas (TVA) (N = 34) from 37 FAP patients. Proliferative activity was determined by cell cycle distribution analysis. In addition, transcriptional capacity was determined by chromatin in situ testing. For both, DNA flow cytometry was used. Cycling cells were identified by immunohistochemical staining with monoclonal antibody Ki67. The existence of subdiploid apoptotic cells was derived from DNA and/or DNA/protein patterns. In a follow-up group, the mucosa is characterised by a balance between proliferation (S % + G2M % = 19) and apoptotic cells (% = 17). The percentage of Ki67 positive cells (16%) corresponds to the percentages mentioned above. In TA, the amount of apoptotic cells remains unaltered, in TVA it decreases to 8%. At the same time, the percentage of Ki67 positive cells increases significantly in both TA and TVA (39%, 42%). With patients who underwent surgery due to clinical signs without histological evidence for malignancy, apoptotic cells in TA continue to decrease significantly (9%), without any changes in cycling cells. Only in the carcinoma-bearing bowel, cycling cells increase to 52%. Here, the percentage of apoptotic cells in TVA reaches the lowest level (5%). A connection between proliferation and apoptosis was observed in mucosa and TVA. The process of tumorigenesis is characterised by a stepwise increase in resistance to apoptosis followed by an increase in cycling cells.

Adenoma↗

Leuko-reduction using an integral Sepacell filter early (4 h, 24 h) or late (48 h, 120 h) after plateletpheresis does not affect platelet function.

Leuco-reduction of aliquots of single-donor platelet concentrates with an integral Sepacell PLS-5A filter was performed 4, 24, and 48 h after apheresis including a control after 120 h (not recommended by the manufacturer) to evaluate the effect of both early and late filtration on the concentrates in a paired study. Highly efficient (> 2 log10) leuko-reduction was consistently observed for filtration any time after apheresis. Various proaggregatory stimuli were tested to determine the stimulus concentration (EC50 values) required for half-maximal aggregation of platelet samples (200 platelets/nl). Neither glycoprotein IIb/IIIa-dependent (thrombin-, collagen-, and APD-induced) nor glycoprotein Ib-mediated (ristocetin-induced) platelet function were affected by filtration 4, 24, 48, or 120 h after plateletpheresis. For single-donor plateletpheresis using a closed system with an integral Sepacell filter, our in vitro results suggest that the timing of leuko-reduction does not affect the platelet-dependent hemostatic qualities of the product.

Equipment Design↗

Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

OBJECTIVE: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes. DESIGN: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design. SETTING: 15 university hospitals or affilliated clinics. PATIENTS: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment. INTERVENTION: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone. MEASUREMENTS: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinical visit. An intention-to-treat analysis was used. RESULTS: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group. CONCLUSIONS: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life.

Acyclovir↗

Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I).

The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.

Animals↗

Uterine inversion after nitroglycerin use during cesarean delivery.

Intravenous nitroglycerin was used to provide uterine relaxation for cesarean delivery of a macrosomic infant. The procedure was complicated by uterine inversion, and subsequent uterine atony. While several other factors may have contributed to the uterine atony, nitroglycerin administration might have played a role. Further, while nitroglycerin was helpful in facilitating the delivery of the macrosomic infant, the risk of uterine inversion must be considered.

Journal Article↗

Predictors of sun exposure in adolescents in a southeastern U.S. population.

PURPOSE: With the increase in melanoma incidence, the sun exposure and protective behaviors of adolescents are of great concern. Limited data are available on the prevalence and predictors of risk behavior in adolescents in the southeastern United States. This study examined the levels of sun exposure and variables predictive of sun exposure among adolescents in two Alabama middle schools. METHODS: A total of 509 sixth-graders completed a self-administered survey assessing: (a) their knowledge, attitudes, and beliefs about malignant melanoma; and (b) their sun exposure and sunburns for a specific weekend and for the summer. RESULTS: Levels of sun exposure and frequency of sunburn were high. Regression models determined the predictors of weekend and summer sun exposure, and weekend sunburn. Significant predictors varied by outcome and included gender, perceived importance of a suntan, parent and peer modeling, and sunscreen use. CONCLUSION: Reducing the risk of melanoma will require a three-pronged intervention strategy with efforts directed at adolescents, their parents, and the broader community.

Adolescent↗

[Ultrasound diagnosis of acute appendicitis--possibilities and limits of the method--results of prospective and retrospective clinical studies].

AIM: In the diagnosis of appendicitis high-resolution ultrasound has become "gold standard" among the imaging methods. The ranking of the method and its dependence on the experience of the examiner, the quality of different ultrasound machines and the time of the examination, were examined in a trial during a 7-year period. METHOD: In 905 patients examination by the surgeon was followed by ultrasound. The results were compared with clinical or histological diagnosis. RESULTS: In a prospective study we examined sonographical 367 patients with the diagnosis of "appendicitis" at admission. The sensitivity was 75.3%, the specificity 96.2%. In a retrospective analysis of 538 patients with appendectomy, the sensitivity was 50.5% and the specificity 95.4% in pre-operative diagnosis. If the examination was done by a less experienced examiner (less than 500 ultrasound examinations/year) the sensitivity was 45.1% and specificity 93.6%; an experienced doctor (500-1000 ultrasound examinations/year) achieved 57.9 and 92.9% and a highly qualified investigator (more than 1000 ultrasound examinations/year) a sensitivity of 73.9% and a specificity of 97%. If the examination was realised with high frequency ultrasonic scanning (10 MHz), sensitivity (73.9%) and specificity (96.3%) could be increased. Essential for an exact diagnosis was a short-term period between ultrasound examination and intra-abdominal diagnosis. CONCLUSION: Optimal sonographical appendicitis diagnosis must be based on a combination of a qualified examiner, high-resolution ultrasound and short-term follow-up.

Acute Disease↗

[Complications of fine needle puncture. DEGUM survey II].

AIM: In a follow-up survey of the members of the German Society for Ultrasound in Medicine (DEGUM), the use of several fine-needle puncture techniques as well as the frequency and nature of the complications were assessed. METHOD: A questionnaire was sent to all 3364 members of the society. RESULTS: 95070 fine-needle punctures were reported. Of these, 66379 were done to obtain cytological material (69.8%), 19633 (20.7%) to obtain histological material and 9057 (9.5%) for therapeutic reasons. 38.6% of the punctures were guided by ultrasound (i.e. performed without ultrasonic observation of the puncture process), 35.1% were conducted under ultrasonic view and 26.3% with a special puncture probe. The punctures for cytology were generally done without direct ultrasonic observation (45.6%); the punctures for histology were performed for the most part with puncture probes (56.7%). The therapeutic punctures were monitored with a puncture probe in 52.5%. In 95070 punctures, 765 complications were observed (0.81%), one death (0.0011%) and six metastases in the puncture canal (0.0063%); 0.71% slight and 0.095% severe complications were recorded. The punctures for cytology caused the fewest complications with 0.59%. Those for histology had a complication rate of 0.99% and the therapeutic punctures one of 1.98%. In comparison to our first survey in 1988, complications increased from 0.51% to 0.81% primarily because of increased slight complications, which rose from 0.44% to 0.71%. The severe complications rose from 0.057% to 0.095%. Deaths decreased from 0.0075% to 0.0011%. Metastases in the puncture canal were likewise observed more frequently than in the first survey (0.0063% versus 0.003%). The increase in frequency of complications was predominantly the result of a more careful registration, but also by a wider use of the techniques. CONCLUSION: Ultrasonically guided fine-needle puncture is a method with a low rate of complications, but even this slightly invasive method requires stringent indications.

Biopsy, Needle↗