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Biomedical subjects

J Welter

Publications and source records attributed to J Welter.

At least 19 recordsLinked to original sources
PubMed2003

Suppression of third-order intermodulation in a klystron by third-order injection.

The first observations and measurements are reported on suppression of the third-order intermodulation (IM3) product arising from nonlinear mixing of two drive frequencies in a klystron, by externally injecting a wave at the IM3 product frequency. Optimum amplitude and phase of the injected wave for maximum suppression are examined. Results indicate that suppression of the IM3 product by as much as 30 dB can be achieved. Experimental results compare favorably with predictions of a 1D simulation code that takes into account all kinematical and dynamical effects including charge overtaking and space charge forces.

Journal Article↗
PubMed2000

Thapsigargin suppresses phorbol ester-dependent human involucrin promoter activity by suppressing CCAAT-enhancer-binding protein alpha (C/EBPalpha) DNA binding.

Human involucrin (hINV) is a keratinocyte differentiation marker expressed in the suprabasal epidermal layers. In cultured keratinocytes hINV mRNA levels are increased 10-fold by a 24-h treatment with 50 ng/ml PMA, an agent that promotes keratinocyte differentiation. Previous studies show that thapsigargin (TGN), an agent that depletes intracellular calcium stores, inhibits keratinocyte differentiation. In the present study we show that TGN inhibits the PMA-dependent, differentiation-associated, increase in hINV mRNA levels and hINV promoter activity. Inhibition is half-maximal at 10 nM and maximal at 100 nM TGN. Neither basal hINV promoter activity nor glyceraldehyde-3-phosphate dehydrogenase mRNA levels are inhibited. Mutation of a functionally important CAATT-enhancer-binding protein (C/EBP) site within the hINV promoter proximal regulatory region eliminates the regulation, suggesting that TGN may effect C/EBP-dependent promoter activation. Consistent with this hypothesis, TGN inhibits C/EBPalpha-dependent promoter activation via a mechanism that involves inhibition of C/EBPalpha binding to DNA without changing C/EBPalpha protein levels. These results suggest that TGN interferes with hINV expression by interfering with C/EBP transcription-factor function.

Base Sequence↗
PubMed2000

Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 +/- 0. 25) than did i.n. immunization with NYVAC-HF (0.88 +/- 0.36; n = 9) and ALVAC-HF (0.61 +/- 0.43; n = 9, P = 3 x 10(-7)), and survival was also significantly better in the i.n.-parenteral group (3 of 9) than in the other HF-vaccinated animals (none of 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple routes were not tested with the ALVAC vaccine. The results suggest that infant ferrets are less responsive to i.n. vaccination than are older ferrets and raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.

Administration, Intranasal↗
PubMed1999

Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines.

Animals↗
PubMed1998

[Diagnostic value of somatostatin receptor scintigraphy with indium-111 pentetreotide in small-cell bronchial carcinoma].

Small-cell lung cancer (SCLC) cells may express somatostatin receptors [14]. Receptor-positive tissue can be visualised in vivo by scintigraphy with radiolabelled somatostatin analogues. In a prospective study we examined 18 patients with histologically proven SCLC for the diagnostic value of somatostatin receptor scintigraphy using indium-111 pentetreotide. Planar whole body scanning was performed 4 and 24 hours after administration. Additional SPECT imaging of the thorax and the abdomen was done at 24 hours. The results were compared with conventional staging procedures: ultrasound, x-ray, computed tomography and bone scintigraphy. In all 18 patients the primary tumour was correctly identified. Out of 13 patients with mediastinal lymphoma formation 10 patients showed positive SRS. In 2 more patients SRS showed mediastinal uptake while CT scanning was negative. The detection of distant metastases in patients with extensive disease was true positive in 8 cases (OSS, HEP, BRA), false negative in 4 cases (PLE, ADR, HEP), corresponding to a sensitivity of 67%. In 2 patients cerebral metastases were no longer detectable by SRS after previous local irradiation. Even though the method is limited in respect of revealing distant metastases in the upper abdominal area due to physiological uptake in liver, spleen and kidneys, differentiation between limited disease (LD) and extensive disease (ED) was possible in all cases. We conclude that [111In]pentetreotide scintigraphy is a suitable method for the detection of SCLC primary tumours and a substantial tool for differentiation between LD and ED if combined with ultrasonography of the upper abdomen.

Adult↗
PubMed1997

Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

Animals↗
PubMed1990

Detection of histamine release inhibitory factor- and histamine releasing factor-like activities in bronchoalveolar lavage fluids.

Histamine releasing factors (HRF) are a group of cytokines that cause degranulation of basophils and mast cells. Recently we have described a histamine release inhibitory factor (HRIF) that inhibits HRF-induced histamine release from basophils and mast cells. The objective of this study was to investigate the presence of these cytokines in bronchoalveolar lavage (BAL) fluid from normal subjects. We found that BAL fluids from 12 to 17 volunteers contained a dialyzable (molecular weight cutoff 3500) factor that inhibited basophil histamine release by HRF, anti-IgE, concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, BAL fluids from 83% of the tested donors contained a nondialyzable inhibitor that blocked HRF-induced histamine release from basophils. The molecular weight of this inhibitor was estimated to be 20 to 30 and 8 to 10 kD by Sephadex G-50 chromatography and TSK 2000 size-exclusion HPLC. None of the unconcentrated BAL fluids showed any HRF activity on initial screening using basophils from allergic subjects. However, when the BAL fluids were concentrated, all BAL samples that were tested (N = 10) demonstrated significant HRF activity. The molecular weight of BAL HRF has been estimated to be in the range of 15 to 25 kD by size-exclusion HPLC, similar to the HRF synthesized by mononuclear cells. Thus we have demonstrated the presence of both HRF and HRIF in the BAL fluids. We speculate that these cytokines may be involved in the local regulation of basophil and mast cell activation.

Adult↗
PubMed1983

[Comparative circulatory studies during implantation of total endoprostheses using methylmethacrylate and BDF cement].

In every ten patients undergoing elective surgery for total hip prosthesis methylmethacrylate and BDF cement respectively were used for the implantation of the prosthesis. The results of the haemodynamic investigation demonstrate that improvement of the surgical procedure may reduce the incidence of haemodynamic parameters: After implantation of methylmethacrylate into the femoral shaft the arterial pressure decreased from 95.9 +/- 13 to 86 +/- 11 torr (P less than 0.05); the left ventricular stroke work index dropped from 49.9 +/- 5 to 42.1 +/- 7 g.m/m2 (P less than 0.01). While total peripheral resistance decreased slightly in the methylmethacrylate group, there was a small increase after implantation of BDF cement into the femoral shaft. In both groups, however we found a slight elevation of pulmonary vascular resistance after cement implantation into the femur. The determination of the serum concentration of the cement monomer did not yield any measurable serum concentrations. Heat production by polymerisation of BDF cement (maximum 45.8 +/- 6.5 Centigrade) was much less compared with the temperature which developed during the polymerisation of methylmethacrylate (maximum 63 +/- 16.4 Centigrade); therefore, the safety of clinical application seems to be greater with the new BDF cement.

Aged↗
PubMed1982

[Pharmacokinetic investigations on the penetration of mezlocillin into the pleural fluid].

5 g of mezlocillin were administered by a 30 minute drip infusion to each of ten patients (mean age 59.4 years). Antibiotic concentrations in serum and pleural fluid were assayed microbiologically at regular intervals. The antibiotic concentrations determined 1.5 and 8 hours after beginning the infusion were between 83.9 and 4.0 mg/l in the serum and 53.1 and 6.5 mg/l in the pleural fluid. A comparison of the mean antibiotic concentration found in the pleural secretions (22 mg/l) with the minimal inhibitory concentrations of clinically relevant pathogens shows that mezlocillin covers 69% to 84% of the pathogen spectrum. Mezlocillin can thus be used in the therapy of infectious pleural effusions.

Aged↗
PubMed1982

[Antibiotic concentrations in the abdominal cavity as basis for antibacterial therapy of peritonitis: penetration of mezlocillin into the peritoneal exudate].

The importance of the antibiotic concentration in peritoneal exudate is emphasized as a criterium for the possible success of antibiotic therapy of intra-abdominal infections. 5 g of mezlocillin were given i. v. over 15 min to ten patients with a mean age of 56 years. The serum concentrations, assayed microbiologically, were: 299.5 mg/l at the end of the infusion, 103.2 mg/l, 18.6 mg/l and 2.1 mg/l 60, 240 and 480 min after the end of the infusion, respectively. The serum half-life T1/2 beta, calculated from the beta phase, was 67 min. In the peritoneal fluid the peak concentration of Cp = 42.0 mg/l was achieved after 2.2 h. A quarter of this concentration was maintained in the peritoneal cavity for five to six hours. This concentration inhibited 74% of the 322 pathogens isolated from 123 intra-abdominal infections.

Ascitic Fluid↗
PubMed1982

[Staged lavage therapy in diffuse peritonitis].

Sequential lavage is introduced as a new treatment for severe diffuse purulent peritonitis. Following surgical removal of the focus and intraoperative intraabdominal lavage, the sequential lavage technique was applied with length of treatment dependent on the severity of each case. Data from 21 patients were recorded for the study. Subject lethality was 19%. Three patients survived the so-called "incurable triad".

Drainage↗
PubMed1981

Ticarcillin therapy of risk patients with infections due to Pseudomonas aeruginosa.

The implication of nosocomial infection due to Pseudomonas aeruginosa is demonstrated by comparing the bacteriological findings with the clinical picture of ten patients in a surgical intensive care unit. The occurrence of this organism and its resistance to beta-lactam-antibiotics and aminoglycosides is demonstrated. Ticarcillin was administered to ten patients following bacteriological and clinical evidence of infections due to P. aeruginosa. The pathogenicity of P. aeruginosa as an organism complicating the course of severely injured patients is discussed. Therapeutic consequences in regard to possible combination with other antibiotics are suggested.

Adolescent↗
PubMed1980

[Effect of metoprolol on the circulation after head trauma. Studies during continuous intravenous administration (author's transl)].

The influence of continuous intravenous administration of metoprolol on heart rate and haemodynamics was tested in ten unconscious patients who, after sustaining a head injury, developed sinus tachycardia due to increased sympathicotonia. In preliminary studies on three patients the effective dosage for heart rate reduction was determined. Following this, seven patients received 0.15 mg/kg . h of metoprolol over 36 hours. Heart rate decreased from an average of 127.5 to 78.8/min, a statistically significant reduction. Stroke volume index significantly rose from an average of 35.5 to 52.3 ml/m2, while other haemodynamic variables were not or only slightly changed. Cardiac index fell (not significantly) from 4.51 to 3.81/min . m2, peripheral vascular resistance rose (not significantly) form 942.4 to 1061.7 dyn . s . cm-5. Arterial and pulmonary artery pressures as well as filling pressures of right and left ventricle and left ventricular work index were not altered. Total oxygen consumption and oxygen extraction rate also remained unchanged. Measurement of metoprolol plasma levels in four patients excluded the possibility of a cumulative effect.

Adult↗