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Biomedical subjects

W Frank

Publications and source records attributed to W Frank.

At least 37 records · Page 2Linked to original sources
PubMed2000

Water deficit triggers phospholipase D activity in the resurrection plant Craterostigma plantagineum.

Phospholipids play an important role in many signaling pathways in animal cells. Signaling cascades are triggered by the activation of phospholipid cleaving enzymes such as phospholipases C, D (PLD), and A(2). Their activities result in the formation of second messengers and amplification of the initial signal. In this study, we provide experimental evidence that PLD is involved in the early events of dehydration in the resurrection plant Craterostigma plantagineum. The enzymatic activity of the PLD protein was activated within minutes after the onset of dehydration, and although it was not inducible by abscisic acid, PLD activity did increase in response to mastoparan, which suggests a role for heterotrimeric G proteins in PLD regulation. Two cDNA clones encoding PLDs, CpPLD-1 and CpPLD-2, were isolated. The CpPLD-1 transcript was constitutively expressed, whereas CpPLD-2 was induced by dehydration and abscisic acid. Immunological studies revealed changes in the subcellular localization of the PLD protein in response to dehydration. Taken together, the data on enzymatic activity as well as transcript and protein distributions allowed us to propose a role for PLD in the events leading to desiccation tolerance in C. plantagineum.

Abscisic Acid↗
PubMed2000

Feedback-controlled negative pressure ventilation in patients with stable severe hypercapnic chronic obstructive pulmonary disease.

BACKGROUND: In recent studies, the efficacy of intermittent rest of the inspiratory muscles as an option of treating patients with severe chronic obstructive pulmonary disease (COPD) has become questionable. OBJECTIVE: The aim of our study was to analyze the effects of feedback-controlled intermittent negative pressure ventilation (INPV) on stable, but severely hypercapnic COPD patients. METHODS: 21 clinically stable, hypercapnic patients with severe COPD underwent INPV with chest shells for 3 weeks, 6 h a day. The INPV sessions were optimized by a visual biofeedback system, which enabled control over the decrease in diaphragmatic activity. Respiratory muscle (RM) function parameters, lung function parameters, blood gases and exercise capacity were analyzed. RESULTS: In the end, 19 patients concluded INPV treatment. They had PaO(2) of 56.5 +/- 11.8 mm Hg, PaCO(2) of 50.2+/-2.7 mm Hg (mean +/- SD) and FEV(1) of 27.8 +/- 4.3% predicted before treatment. There was no statistically significant change in lung function parameters, RM function parameters, physical performance and level of dyspnea after 3 weeks of INPV. CONCLUSION: We conclude that intermittent RM rest induced by INPV can relax inspiratory muscles in most patients with stable severe COPD, but fails to improve RM function and exercise capacity.

Aged↗
PubMed1999

Association between endometrial cancer and tamoxifen treatment of breast cancer.

A retrospective cohort-study in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifen-treated women were analysed. Two thousand four hundred and eight non-tamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twenty-five women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups. In conclusion, this retrospective study demonstrated a non-significant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.

Breast Neoplasms↗
PubMed1999

Tumor flow in malignant breast tumors measured by Doppler ultrasound: an independent predictor of survival.

The purpose of this study was to investigate tumor blood flow in breast cancers with regard to its impact on the overall survival of patients. Tumor blood flow was assessed in seventy-four patients with primary breast cancer by the use of color-coded Doppler ultrasound techniques. Preoperatively obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Color Doppler signals were detected in 71 (96%) of the breast tumors. Out of 74 patients, 17 experienced a relapse or distant metastasis, and 15 women had died due to breast cancer at the time of data analysis. The mean Vmax of the patients who had died was 0.27 m s(-1), whereas survivors showed a mean Vmax of 0.16 m s(-1) (p = 0.01). Vmax, nodal status, and progesterone receptor status remained the only significant factors of overall survival in the multivariate model, whereas tumor size, tumor grade, and estrogen receptor status failed to retain prognostic significance. Moreover, Vmax was identified as the most important prognostic marker for survival in our series. The five-year-survival was 82.3% in Vmax < or = 0.25 m s(-1) patients versus 36.6% in women with tumor flow greater than 0.25 m s(-1). Patients with Vmax > 0.25 m s(-1) experienced a 4.33-fold increased risk of death secondary to the underlying disease. In summary, our data showed that tumor blood flow velocity measured by ultrasonography is an independent prognostic factor of survival in breast cancer patients. Furthermore, tumor flow velocity allows identification of patients at very high risk of death due to breast cancer. Large scale clinical trials should evaluate the clinical usefulness and future impact of this procedure for adjuvant treatment decisions.

Adult↗
PubMed1999

Low dose cabergoline induced interstitial pneumonitis.

Certain dopaminergic anti-Parkinson drugs (ergolines) have repeatedly been identified as a cause of pleuropulmonary disease with a focus on serosal cell damage. Recently, a pathogenetic link between ergolines and prior asbestos exposure was suggested, as regards the development of pleural pathology. This report describes a patient with idiopathic Parkinson's disease, who was on a multiple drug regimen including low dose cabergoline. The patient developed a febrile illness with widespread bilateral lung infiltrations nonresponsive to beta-lactam and macrolide antibiotics. Bronchoalveolar lavage and transbronchial lung biopsy showed a "hypersensitivity-like" interstitial lung disease, which cleared almost completely within 2 months after simple drug withdrawal. Circumstantial evidence suggests a so far undescribed adverse lung reaction to cabergoline, devoid of the more usual pleural changes.

Aged↗
PubMed1999

A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness.

Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.

Amino Acid Sequence↗
PubMed1999

Pulmonary function after total laryngectomy.

OBJECTIVE: To present data on pulmonary function in 59 laryngectomees using a specially designed silicone adapter for connection of the stoma to the bodyplethysmograph. STUDY DESIGN: Prospective assessment of pulmonary function in 59 patients, and comparison of lung function before and after bronchodilator testing in selected cases. METHODS: The usefulness of the adapter was examined. Data of patients with airway obstruction were tabulated according to large airway obstruction (LAO), peripheral airway obstruction (PAO), and small airway disease (SAD) types. RESULTS: Findings show that pulmonary airway obstruction was present in 81% of patients and normal pulmonary function was present in only 11 of the 59 participants (19%). LAO was found in 25%, PAO in 17%, and SAD in 39% of cases. Emphysema was diagnosed in 14% of cases within the above-mentioned LAO and PAO groups. Improvement of pulmonary function was achieved in 12 of 16 laryngectomees with airway obstruction, when a bronchodilator aerosol was administered. In 60% of cases with LAO and PAO, the laryngectomees did not know of any marked obstruction of their airways, and only 10% of those knowing about their obstruction received appropriate medical treatment. CONCLUSIONS: These results suggest that 42% of the laryngectomees tested may have benefited from further medical treatment. After laryngectomy, pulmonary function assessment was performed elsewhere in 1 of 59 cases. In light of the high prevalence of airway obstruction in laryngectomees, more frequent postoperative assessments of pulmonary function should be offered to prevent or to reduce impairment of respiratory function in this postlaryngectomy vulnerable pulmonary status. Further studies are also needed to determine the effects of therapeutic intervention, e.g., assessment of therapy outcome and influence on quality of life.

Aged↗
PubMed1998

Synthesis of 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine and novel derivatives free of positional isomers. Potent inhibitors of cAMP-specific phosphodiesterase and of malignant tumor cell growth.

7-Benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine (7a) is a potent inhibitor of the cAMP-specific phosphodiesterase isoenzyme family PDE4 and induces growth inhibition in a panel of tumor cell lines. In this study, we describe a synthesis that yields 7a and novel derivatives free of positional isomers. The synthesis of alkylamino substituted pteridines is based on the successive nucleophilic aromatic substitution of the chlorine atoms of 2,4,6, 7-tetrachloropteridine. For the reaction with secondary amines, the positional order of reactivity was found to be C4 > C7 > C2 > C6. Final structural proof is given by X-ray crystallography. To unravel structural elements of 7a crucial for the interaction with the target enzyme, the compound was modified systematically. The impact of the modifications on activity was tested by evaluating the ability of the compounds to inhibit cAMP hydrolysis by cAMP-specific phosphodiesterase (PDE4) purified from the solid human large cell lung tumor xenograft LXFL529. Growth inhibitory properties were determined by in vitro treatment of the respective cell line LXFL529L using the sulforhodamine B assay (SRB). The results show that for high activity, the heterocyclic substituent in position 2 of the pteridine ring system requires the presence of a basic nitrogen in 4'-position, as represented by piperazine.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Two dehydration-inducible transcripts from the resurrection plant Craterostigma plantagineum encode interacting homeodomain-leucine zipper proteins.

The molecular dissection of desiccation tolerance in the resurrection plant Craterostigma plantagineum led to the isolation of two dehydration-stress inducible homeo-domain-leucine zipper genes (CPHB-1 and -2). When the coding region of CPHB-1 was used as bait in the yeast two-hybrid system, the ability of CPHB-1 to form homodimers was demonstrated. The two-hybrid system was also used to isolate CPHB-2, which heterodimerises with CPHB-1. Both transcripts are inducible by dehydration in leaves and roots, but steady state levels vary in response to exogenously applied ABA. Although expression of CPHB-1 is not inducible by ABA, the transcript level of CPHB-2 increases during ABA-treatment. Both genes are expressed at very early stages of dehydration and thus may be involved in the regulation of gene expression during dehydration. CPHB-1 and -2 differential expression in response to ABA suggests that they act in different branches of the dehydration-induced signalling network. In vitro binding studies revealed that CPHB-1 specifically binds to the pseudopalindromic sequence CAAT(C/G)ATTG. Using this element for in vitro binding studies with nuclear proteins from dehydrated leaves, an inducible DNA-protein complex was identified.

Abscisic Acid↗
PubMed1998

Effect of testosterone on Leishmania donovani infection levels of murine bone marrow derived-macrophages.

AIM: To investigate the effect of the male sex hormone, testosterone (Te), on Leishmania donovani infection levels of bone marrow derived macrophages(BMMs) from female mice of strain C57BL/6J. METHODS: After three weeks of Te-treatment, the BMMs were isolated, challenged with L. donovani at a ratio of 10 to 1 promastigotes per macrophage, and the infection levels of different time points were monitored by Giemsa staining. RESULTS: BMMs from Te-treated mice had a significantly increased initial uptake(3 h post infection, P < 0.05) of promastigotes and carried heavier infection levels at all time points(24 h, 48 h, 72 h post infection, P < 0.01), compared with those from oil treated controls. CONCLUSION: Te can increase L. donovani infection levels of BMMs, being possibly related to Te-induced immunosuppression.

Animals↗
PubMed1998

[Report on the current knowledge of Vienna primary school teachers about bronchial asthma in children].

PURPOSE: This study was performed to examine the causes, triggers and therapy of bronchial asthma in a statistically relevant group of teachers at primary schools in Vienna. Furthermore, it was intended to investigate the correlation between their knowledge and their approach in respect of the management of asthmatic pupils. METHODS: 1054 (80.4%) of 1311 questionnaires were returned and evaluated. Five items were investigated: "general knowledge", "symptoms and triggers"; "exercise", "treatment" and "individual experience". Statistical analysis was performed by using counting statistics. For the correlation of items, Spearman correlation coefficients and Wilcoxon's test were used. RESULTS: The teachers in primary schools showed a good basic knowledge of asthma and its symptoms. Poor understanding was found with regard to the medical treatment and trigger factors of asthma; only 34% of the teachers knew that playing games in cold wind may provoke an exacerbation of asthma; less than half of the teachers (45%) were aware of the fact that an asthma attack can be prevented by prophylactic treatment. A significantly positive correlation was found between previous instruction on asthma and its management, the degree of individual experience, and the correct belief that asthmatic children should be encouraged to fully participate in school sports and activities (p = 0.001). Most of the teachers (94%) felt the lack of sufficient information. Only 2% had received proper instruction on asthma and revealed a significantly better knowledge of all items (p = 0.0001). CONCLUSION: We suggest that teachers at primary school receive further instruction on asthma, especially regarding its practical aspects.

Adult↗
PubMed1997

Report of 337 patients with renal cell carcinoma emphasizing 110 with stage IV disease and review of the literature.

BACKGROUND: In the literature, the interdependence of variables, including stage, sex, age, tumor size, therapy, and survival, is complex. The size variable has heretofore received relatively little emphasis. METHOD: This was a retrospective evaluation of 337 patients with kidney cancer treated at the University of Illinois Affiliated Hospitals. Data were collected on stage, sex, age, tumor size, TNM stage, therapy, and survival. Statistical analyses included Kaplan-Meier 5-year survivals, as well as multivariate analysis utilizing the Cox regression model. A subset of 110 patients with TNM Stage IV disease is further evaluated employing a multivariate analysis. The principal form of therapy was nephrectomy. RESULT: Five-year survivals by stage varied from 100% for Stage I, 96% for Stage II, 59% for Stage III, to 16% for Stage IV. In the subset of 110 patients with TNM Stage IV disease, those with a single metastasis had better survivals than those with two or more. Those having nephrectomy had better survivals (P < 0.05). Therapy (in addition to nephrectomy) was curative (defined as cytotoxic chemotherapy or immunotherapy) in 40 patients and palliative (defined as radiation to bone metastases, hormone therapy, or supportive) in 70 patients. Multivariate analysis of TNM Stage IV variable differences indicated that only tumor size differences and nephrectomy significantly affected survival. CONCLUSIONS: Of importance is the observation that among these patients. Survival is directly correlated with tumor size.

Adenocarcinoma↗
PubMed1997

Efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, an anti-immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis.

The efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, a recombinant monoclonal mouse-human chimeric anti-human immunoglobulin E (IgE) antibody were evaluated for 153 patients with seasonal allergic rhinitis treated with placebo or with 15, 30, or 60 mg CGP 51901 in six biweekly doses. Seasonal allergic rhinitis was chosen to validate the concept of anti-IgE therapy because the causal and temporal relation between allergen confrontation and IgE-mediated evocation of symptoms is firmly established. A sustained 85% or greater reduction of serum free IgE levels was shown to be effective in improving clinical symptoms. The concentration of CGP 51901 needed to maintain 85% or greater reduction of IgE was estimated to be about 5000 ng/ml. Baseline IgE levels and body weights of the patients greatly influenced the pharmacokinetic and pharmacodynamic profiles of CGP 51901. A population model was developed and refined to take into account patient baseline IgE level and body weight. The model was able to help predict multiple-dose pharmacokinetic and pharmacodynamic profiles on the basis of single-dose pharmacokinetic and pharmacodynamic measurements in the therapeutically effective dose range.

Adult↗
PubMed1997

Chemotherapy with praziquantel has the potential to reduce the prevalence of Echinococcus multilocularis in wild foxes (Vulpes vulpes).

In order to evaluate the applicability of anthelminthic treatment of wild foxes (Vulpes vulpes) to limit their infection with Echinococcus multilocularis, bait pellets, each containing 50 mg praziquantel, were repeatedly distributed in an area of 566 km2 where many foxes are infected, in southern Germany. After six baiting campaigns (15-20 baits/km2) over a period of 14 months, the prevalence of the cestode in foxes, initially 32%, had fallen to 4%. The effect was most pronounced in the central part of the treated area, where no positive fox was found in the 2 months before the end of the trial. The study was controlled for other factors that could influence the parasite's prevalence, such as the availability of intermediate hosts. While the potential of this baiting method to remove E. multilocularis from wild hosts has been demonstrated, the question of its long-term efficacy and other unresolved problems have to be addressed by consecutive studies before routine application can be recommended.

Animals↗
PubMed1996

Sarcocystis singaporensis: studies on host specificity, pathogenicity, and potential use as a biocontrol agent of wild rats.

Host specificity and pathogenicity of Sarcocystis singaporensis were investigated as a prerequisite to a subsequent application of the parasite as a biocontrol agent of wild rats in Egypt. After inoculation of 7 snake species comprising the families Elapidae, Viperidae, Colubridae, and Boidae with sarcocysts, sporocyst development was only observed in a reticulated python. Among amphibians, reptiles, and rodents that orally received various sporocyst doses in the laboratory, 2 x 10(4) sporocysts or more were lethal to roof rats Rattus rattus frugivorous, brown rats Rattus norvegicus, and bandicoot rats Nesokia indica. Sarcocysts developed in Rattus spp. and Nile grass rats Arvicanthis niloticus. Subsequently, the pathogenicity of S. singaporensis was tested under natural control situations offering bait pellets containing high amounts of sporocysts to a free-living population of roof rats, which was monitored by indirect census baiting commonly used in rodenticide evaluation. Ten days after consumption of the bait pellets, the infected population collapsed, leading to a control success of 73%. A negative control population, which received a placebo, remained stable. These data demonstrate for the first time that S. singaporensis can be used as a biocontrol agent of wild rats. However, an immunization experiment with roof rats in the laboratory showed that these are capable of mounting a rapid specific immune response resulting in survival of acute sarcocystosis.

Amphibians↗
PubMed1996

Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs.

BACKGROUND AND DESIGN: No controlled studies exist with regard to the risks of continuing therapy with warfarin sodium or platelet inhibitors or the benefits of briefly discontinuing therapy with these agents in patients who are undergoing cutaneous surgical procedures. Our objective was to determine the frequency of complications of cutaneous surgery in patients who were receiving warfarin or platelet inhibitors and to evaluate whether preoperative discontinuation reduces complications. A retrospective, controlled study was performed of complications of excisional and Mohs micrographic surgery in 653 patients who were being treated with warfarin or platelet inhibitors or with their medications being briefly withheld. RESULTS: Severe complications of cutaneous surgery in patients who are taking warfarin or platelet inhibitors are uncommon, occur in 1.6% of cases, and are not significantly increased compared with complications in control subjects. Furthermore, there was no statistically significant reduction in the rates of severe complications in patients who had their medications preoperatively held. CONCLUSION: Cutaneous surgery in patients who receive warfarin or platelet inhibitors is associated with a low risk of severe complications, not significantly reduced by brief preoperative discontinuation.

Adolescent↗