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Biomedical subjects

B Mueller

Publications and source records attributed to B Mueller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Evidence for multivalent structure of T-cell antigen receptor complex.

The T-cell antigen receptor (alpha beta or gamma delta TCR) is known to associate with four polypeptides (CD3 gamma, delta, epsilon and zeta) to form the TCR-CD3 complex. Although the six chains are well characterized, the molecular mass of the TCR-CD3 complex and stoichiometry of the components are currently uncertain. We analysed the TCR of a T-T hybridoma which expresses two distinct heterodimers. When the hybridoma was incubated with a mAb (MR9.2) specific for the V alpha 10V beta 5.1 heterodimer, both of the heterodimers were lost from the cell surface, as measured with mAb MR9.2 and MR9.7 (V alpha 1V beta 1-specific). The ability to co-modulate V alpha 1V beta 1 and V alpha 10V beta 5.1 suggested that TCR complexes could contain two alpha beta-heterodimers. Density gradient sedimentation analysis provided further evidence for higher order TCR. The sedimentation patterns of the TCR were compared to that of the B-cell antigen receptor and the well-characterized VSV membrane G-protein as well as to soluble marker proteins. Maximal cell surface murine and human TCR sedimentation coefficients were substantially greater than the 9-10S predicted for a 210 kDa monovalent alpha beta gamma delta epsilon 2 zeta 2 structure. The TCR sedimented in mild non-ionic detergents as large 18 +/- 3S complexes co-migrating with a 443 kDa marker protein. In contrast, the IgM B-cell antigen receptor had a maximal sedimentation coefficient of 10 +/- 3S, consistent with a predicted size of approximately 300 kDa. Taken together, the results suggested that T-cell antigen receptors can contain more than one alpha beta-heterodimer which could be incorporated into a minimal divalent 10-chain TCR-CD3 complex (e.g. alpha beta gamma epsilon epsilon delta zeta zeta alpha beta).

Animals↗
PubMed1995

Pulmonary malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising in a pediatric HIV-positive patient.

A malignant lymphoma arising in the lung of a pediatric HIV-positive patient exhibited histologic and clinical features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm consisted of a 4-cm mass in the left-upper lobe of the lung of a 7-year-old girl. The lung mass was surgically resected. Monoclonal immunoglobulin heavy and light chain gene rearrangements were shown by Southern blot. Monoclonality of light chain expression was demonstrated by immunohistochemistry. Coexpression of Leu-22 (CD43) by the tumor cells supported the diagnosis of lymphoma. The remainder of the pulmonary parenchyma distal to the mass was associated with pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis, which may have been a predisposing factor. Gastric MALT lymphomas have recently been described in adult HIV-antibody-positive patients. Ours represents the first reported case of a pulmonary MALT lymphoma in a pediatric HIV-positive patient. In addition, at age 7, this is the youngest patient reported with a MALT lymphoma.

Child↗
PubMed1993

Pancreatic cancer detected by positron emission tomography with 18F-labelled deoxyglucose: method and first results.

In order to evaluate the utility of positron emission tomography (PET) with 18F-labelled deoxyglucose (FDG) for detection of pancreatic cancer 15 patients with pancreatic masses shown by computed tomography were investigated. Static PET scans covering an axial field of view of 15 cm were obtained 45 min after intravenous injection of 150-300 MBq FDG. Focally increased FDG accumulation was present in 12 out of 13 patients with histologically proven adenocarcinoma, in particular in eight of nine lymph node and four of five liver metastases. Scans of two patients with chronic pancreatitis confirmed by surgery revealed a normal FDG distribution. Contrast between tumour and normal tissue depended the metabolic situation prior to FDG injection. High ratios were found in fasting patients whereas no elevated FDG uptake was measured in an insulin-dependent diabetic suffering from carcinoma of the pancreatic head. We conclude that FDG PET might have the potential for detection and even differentiation of pancreatic carcinoma from chronic pancreatitis. Further studies are necessary to substantiate these preliminary findings and to optimize results in diabetic patients.

Adenocarcinoma↗
PubMed1993

Viral resistance to the thiazolo-iso-indolinones, a new class of nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

Thiazolo-iso-indolinone derivatives with high specificity toward the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) were identified. The most potent compound, BM +51.0836, inhibited HIV-1 RT at a 50% inhibitory concentration of 90 nM in vitro. In cell culture assays, similar 50% inhibitory concentrations were obtained with high specificity for HIV-1. These substances were equally active against a zidovudine-resistant isolate. No antiviral effect was observed with an HIV-2 isolate. HIV-1 isolates resistant to the thiazolo-iso-indolinones were generated in cell culture, and the nucleotide sequences of the respective RT genes were analyzed subsequently. Comparison of the deduced amino acid sequences with the wild-type sequence showed an amino acid change at position 181 (Tyr to Cys). Substitutions of amino acid Lys-101 and Lys-103 as well as Tyr-181 and/or Tyr-188 by site-directed mutagenesis led to resistance against the thiazolo-iso-indolinones. A chimeric HIV-2 RT, substituted with amino acids at positions 179 to 190 from HIV-1, acquired only partial susceptibility to BM +51.0836.

Antiviral Agents↗
PubMed1992

Treatment of aggressive cytomegalovirus retinitis with ganciclovir in combination with foscarnet in a child infected with human immunodeficiency virus.

Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response.

Antiviral Agents↗
PubMed1991

Serum alpha 1-microglobulin and beta 2-microglobulin for the estimation of fetal glomerular renal function.

As proteins cannot cross the placenta levels of the microproteins alpha 1-microglobulin (alpha 1MG) and beta 2-microglobulin (beta 2 MG) can be used to assess fetal glomerular renal function. alpha 1MG, beta 2MG and creatinine were routinely determined in cord and maternal blood of 133 newborns [gestational age (GA) 25-42 weeks]. Twenty-nine patients with suspected impaired maternal or fetal renal function were studied separately and two fetuses were studied in utero. The mean fetal beta 2MG concentration fell from 3.87 +/- 0.56 mg/l in the 25-31 weeks GA group to 2.60 +/- 0.50 mg/l in the mature newborn group. alpha 1MG concentration fell from 3.10 +/- 0.51 to 2.25 +/- 0.49 mg/dl. In contrast, the mean maternal beta 1MG concentration rose from 1.73 +/- 0.69 mg/l in the 25-31 weeks GA group to a mean of 1.83 +/- 0.48 mg/l in the mature newborn group; alpha 1MG rose from 3.96 +/- 0.58 to 4.33 +/- 1.6 mg/dl. Maternal and fetal creatinine levels were identical. Fetal microprotein levels fall during intra-uterine development as glomerular filtration rate (GFR) rises. There is no correlation between cord blood and maternal alpha 1MG or beta 2MG concentrations. In 13 children with urological anomalies only 1 had elevated microprotein levels and he later developed renal insufficiency. Determination of microprotein levels in fetal serum can be used to detect severe renal function disturbances and to estimate GFR independently of maternal renal function.

Alpha-Globulins↗
PubMed1991

Gestational duration and birthweight in white, black and mixed-race babies.

Using the 1983 United States population of single live births, birthweight and gestational duration were compared for babies of these different parental racial groups: both parents White, mother White-father Black, mother Black-father White, both parents Black. The four groups differed significantly with respect to the usual sociodemographic variables. Mean birthweight and mean gestational duration decreased in that order from the White-White reference group, and conversely there were increasing trends for low birthweight and preterm delivery. Adjustment for the usual sociodemographic variables did not alter these trends appreciably. Group differences were more strongly related to the mother's race than to the father's, and the trends were related to the mother's race. Because the father's race was significant, genetic factors are probably of some importance. The evidence from this study, together with the often-demonstrated relationships between low birthweight and preterm delivery with sociodemographic variables, and the short-term downward secular trends in low birthweight, support the concept that non-genetic maternal factors are more important for these abnormal outcomes. But because neither the usually utilised sociodemographic variables nor genetic factors seem to explain much of the group differences, new approaches are necessary to understand why, irrespective of ethnic group, some women are at excess risk for suboptimal birth outcome.

Adolescent↗
PubMed1990

Acute megakaryoblastic leukemia in children identified by immunological marker studies.

Acute megakaryoblastic leukemia (AMkL), defined by the presence of the platelet-associated glycoprotein IIb/IIIa complex on malignant cells, was diagnosed in 4 (4%) of 103 consecutive children with untreated acute leukemia or 4 (21%) of 19 children with acute nonlymphoblastic leukemia (ANLL). Particular features in the four children with AMkL were an age below 12 months at diagnosis (two patients), the absence of a significant hepatosplenomegaly (three patients), a leukocyte count below 20 x 10(9)/L with only a few blast cells in the peripheral blood (four patients), a technically difficult bone marrow aspiration (three patients), the presence of many megakaryocytes in marrow particles (two patients), and an inconclusive cytochemistry (four patients). The four children with AMkL were treated according to protocols for ANLL and a complete remission was obtained in all patients. One patient died from relapse after 3 months, one patient is a long-term survivor (38+ months), and two patients still on chemotherapy are disease-free for 11+ and 13+ months.

Adolescent↗
PubMed1988

A double-masked comparison of carteolol and timolol in ocular hypertension.

We performed a double-masked study in which 98 patients with ocular hypertension who had been previously treated with timolol received either timolol 0.25% or carteolol 1%, a beta-blocker with intrinsic sympathomimetic activity. The drugs were administered topically twice daily for one month after a one-week washout period. Intraocular pressure was measured at baseline and after one and four weeks of treatment. The appearance of the fundus, external eye, visual fields, tear secretion, blood pressure, and pulse were recorded. Adverse symptoms were elicited using a menu-type questionnaire and an overall judgment of therapy was recorded. Carteolol was as effective as timolol in reducing intraocular pressure. There were significantly fewer patients reporting adverse events overall (P = .019), and eye irritation specifically (P = .02), in the group treated with carteolol.

Administration, Topical↗
PubMed1988

Umbilical cord separation in the normal newborn.

During a 13-month period, 363 infants were followed up through the first six weeks to determine the effect of perinatal factors (birth weight, gestational age, type of delivery, and pregnancy and neonatal complications) on umbilical cord separation. Also, breast-feedings and umbilical cord care were studied. Except for cesarean section deliveries, study infants were similar to all infants (N = 1474) admitted to the same nursery during the study period. Cord separation occurred from days three to 45, with a mean of 13.9 days. Infants born by cesarean section were found to have an increased interval for cord separation when compared with infants born vaginally (mean +/- SD, 15.9 +/- 5.0 days vs 12.9 +/- 4.2 days). In this study, delays in separation of the umbilical cord beyond 3 weeks of age was not associated with an increased risk of infection.

Birth Weight↗
PubMed1988

Concentrations of nicotine, RSP, CO and CO2 in nonsmoking areas of offices ventilated by air recirculated from smoking designated areas.

The exposure of nonsmokers to environmental tobacco smoke (ETS) when smoking is relegated to designated areas that are not separately ventilated is of considerable interest. Concentrations of nicotine, respirable suspended particles (RSP), carbon monoxide (CO), and carbon dioxide (CO2) were measured in offices under different conditions of smoking regulation: smoking prohibited; smoking prohibited areas receiving recirculated air from designated smoking areas; smoking and nonsmoking sections of these designated smoking areas. Nicotine was collected by pumping air for periods of 1-8 hr at 1 L/min through sampling tubes containing a styrene divinylbenzene copolymer. RSPs (5 micron cut-off) were measured using an optical side scattering instrument. CO was measured by a direct reading electrochemical analyzer and CO2 by colorimetric detector tubes. Detection of nicotine in nonsmoking office areas that received recirculated air from smoking designated areas required sampling times of 4 hr or more. Nicotine levels in such offices were approximately 1.0 micrograms/m3. RSP, CO and CO2 concentrations were approximately the same in these offices as compared to nonsmoking offices not exposed to recirculated air from smoking areas. Providing a designated but not separately ventilated smoking area appears to be effective in eliminating most components of ETS from nonsmoking office work areas.

Air Pollutants, Occupational↗