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Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of 5-fluorouracil in plasma and urine by high-performance liquid chromatography.

A relatively simple, sensitive and rapid high-performance liquid chromatographic method is described for measuring the anticancer drug 5-fluorouracil (5-FU) in human plasma and urine. The procedure includes liquid-liquid extraction using ethyl acetate-methanol (95:5) and preparative column chromatography to separate 5-FU from constituents normally occurring in these biological samples. The columns contained a specially modified form of diatomaceous earth, which requires no pre-conditioning washes. Reversed-phase high-performance liquid chromatography was performed on a C18 column (70 mm x 4.6 mm I.D.) with a mobile phase of water-methanol (95:5) and ultraviolet detection (268 nm). The overall recovery from plasma and urine was 91 and 94%, respectively, at the concentration of 50 ng/ml. The determination limit of the assay for 5-FU was 10 ng/ml of plasma and urine. Concentrations of 5-FU between 10 and 500 ng/ml were measured in plasma and urine with a relative standard deviation of 6.8%. In order to evaluate the procedure, plasma and urine samples from three patients treated with 5-FU by continuous intravenous perfusion, were investigated.

Breast Neoplasms↗
PubMed1992

Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin.

We report on the requirements that have to be met to combine a standard-dose chemotherapy regimen with broad antitumor activity with the mobilization of peripheral blood hematopoietic progenitor cells. Thirty-two cancer patients were given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide, and cisplatin (VIP; n = 46 cycles), followed by the combined sequential administration of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients received GM-CSF alone or were treated without cytokines. Maximum numbers of peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841) in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF-treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated without cytokines. In parallel, there was an increase in myeloid (10,490 colony-forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400), as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood; range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte, monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less precursor cells of all lineages were mobilized, particularly multipotential progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of CD34+ cells and clonogenic progenitor cells could be recruited in intensively pretreated patients. Our data document that after standard-dose chemotherapy-induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC, which might shorten the hematopoietic recovery after high-dose chemotherapy in chemosensitive lymphomas or solid tumors.

Adult↗
PubMed1992

Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Percutaneous endoscopic laser discectomy (PELD). A new surgical technique for non-sequestrated lumbar discs.

Basic features and techniques of percutaneous endoscopic laser discectomy are described and the results in 6 patients reported. Indications are: discogenic radicular symptoms, caused by disc protrusions, which do not respond to conservative treatment. Contra-indications are: major neurological deficit, segmental instability and spondylolisthesis, extruded disc prolapse, narrow spinal canal or lateral recess.

Adult↗
PubMed1992

Human cytomegalovirus (HCMV)-specific immunoglobulin E as a serologic marker for HCMV infection in immunocompromised patients.

An antibody capture assay using an enzyme-linked human cytomegalovirus (HCMV) antigen for the detection of specific immunoglobulin E (IgE) was established. IgG, M, and E responses to HCMV were studied in 497 sera obtained from 44 renal transplant recipients and 51 acquired immunodeficiency syndrome (AIDS) patients. The results were compared with those obtained from 58 HCMV-seropositive healthy individuals. HCMV-specific IgE was detected in 11 (91.7%) renal transplant recipients with primary HCMV infection. In contrast, antibodies of the IgG and IgM classes were detected in only 6 (50.0%) of these patients. Specific IgE was detected in 10 (90.9%) out of 11 renal allograft recipients suffering from secondary HCMV infection. Significant IgG titer rises and IgM were detected in 2 (18.2%) and 6 (54.6%) of these patients, respectively. IgG titer rises and IgM and IgE antibodies were seen in 5 (12.2%), 1 (2.4%) and 18 (43.9%) AIDS patients respectively. All healthy immunocompetent HCMV-seropositive individuals were tested IgE negative. The results obtained in our study indicate that IgE against HCMV is a more reliable serologic marker for primary and secondary HCMV infection than IgM in immunocompromised individuals, especially in organ transplant recipients, since it is not affected by the prophylactic application of HCMV hyperimmune globulin preparations.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Comparison of shell viral culture and serology for the diagnosis of human cytomegalovirus infection in neonates and immunocompromised subjects.

The present retrospective study compares the laboratory diagnosis of cytomegalic inclusion disease (CID) by the use of "shell vial culture" [i.e., immunoperoxidase staining of human cytomegalovirus (HCMV) early antigen in human fibroblasts 24 h postinoculation] to the results of serology (i.e. immunoglobulins IgG, IgM, and IgA HCMV antibody testing) in 21 infants with congenital or postnatally acquired HCMV infection, 5 patients with lymphoproliferative disorders, 35 human immunodeficiency virus (HIV)-seropositive patients who met the Centers for Disease Control (CDC) criteria for stages IVA and IVB of HIV infection, and 115 patients suffering from the acquired immunodeficiency syndrome, AIDS (stages IVC-IVE according to CDC criteria). HCMV infection was diagnosed by means of the shell vial culture inoculated with patient samples (e.g., urine, bronchoalveolar lavage, induced sputum, etc.) and serology in 163 (92.6%) and 65 (36.9%) patients, respectively. Viral shedding was detected by shell vial culture in 100% of the neonates, 80% of the patients suffering from lymphoproliferative disorders, 100% of the AIDS related complex (ARC) and 89.6% of the AIDS patients. In contrast, serologic testing for HCMV-specific antibodies was positive in only 28.6%, 42.9%, and 34.8% of the neonates, ARC, and AIDS patients, respectively. In lymphoma patients, serologic testing gave identical results (80%) to the shell vial culture technique. With the use of the shell vial procedure, active HCMV infection in immunocompromised subjects and neonates can be recognized more reliably than by serologic testing. Nevertheless, in a low percentage of patients (7.4%), virus isolation by the shell vial culture may fail to detect HCMV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Improvement of rotavirus isolation in the cell culture by immune peroxidase staining.

Peroxidase-labeled monoclonal antibody against rotavirus group-specific antigen (inner capsid) was used for the detection of rotavirus by immunoperoxidase staining (IPS) in trypsin-free MA104 cells within 18 h post-inoculation with clinical specimens. One hundred and twenty-one fecal samples from children with acute gastroenteritis were evaluated by IPS, conventional virus isolation in cell culture and a commercially available group A-antigen ELISA (Rotazyme II, Abbott Laboratories). Fifty-eight (47.9%) stool samples were found positive by IPS. In contrast, rotavirus was isolated from only 4 (3.3%) fecal specimens by conventional cell culture (i.e. demonstration of a cytopathogenic effect). A total of 93 (76.9%) samples were positive by ELISA. IPS permits rapid detection of rotavirus infections and detects shedding of infectious virus. The method should be useful for the investigation of nosocomial spread of rotavirus infection in hospitals, contamination of environmental surfaces and desinfectants.

Cells, Cultured↗
PubMed1992

The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.

We have identified and sequenced cDNA clones that encode for the human beta-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human beta-subunit protein is 90% identical to the bovine beta-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the beta-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p 16.3, in the pathogenesis of Huntington disease.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Nonrandom association between Huntington disease and two loci separated by about 3 Mb on 4p16.3.

The gene for Huntington disease (HD) has been localized close to the telomere on the short arm of chromosome 4. However, refined mapping using recombinant HD chromosomes has resulted in conflicting findings and mutually exclusive candidate regions. Previously reported significant nonrandom allelic association between D4S95 and HD provided support for a more proximal location for the defective gene. In this paper, we have analyzed 17 markers, spanning approximately 6 Mb of DNA distal to locus D4S62, for nonrandom association to HD. We confirm the previous findings of nonrandom allelic association between D4S95 and HD. In addition, we provide new data showing significant nonrandom association between HD and 3 markers at D4S133 and D4S228, which are approximately 3 Mb telomeric to D4S95.

Alleles↗
PubMed1992

Exclusion of DNA changes in the beta-subunit of the c-GMP phosphodiesterase gene as the cause for Huntington's disease.

To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Delineation of a 50 kilobase DNA segment containing the recombination site in a sporadic case of Huntington's disease.

No detectable rearrangements involving chromosome 4p16.3 have been observed in patients with Huntington's disease (HD). New mutations for HD could involve structural alterations which might aid the localization of the defective gene. We have reinvestigated a well documented sporadic case of HD. DNA haplotyping with markers between D4S10 and the telomeric locus D4S141 reveals a recombination event in one chromosome of the sporadic HD patient. The site of recombination maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based on the extremely low HD mutation rate and significantly decreased recombination in the distal region of 4p, we hypothesize a direct link between the site of the recombination and HD in this patient.

Adult↗
PubMed1992

[Life saving glance diagnosis in type IIb multiple endocrine neoplasia].

Medullary carcinoma of the thyroid gland is a feature of multiple endocrine neoplasia, type IIb (MEN IIb). The cancer frequently gives rise to metastases in early life. Marfanoid habitus and virtually pathognomic mucosal ganglioneuromas, often situated on the tongue, enable early diagnosis. These stigmata should alert the clinician to the possibility of MEN IIb before medullary carcinoma is clinically manifest. We now believe that it is reasonable to perform a total thyroidectomy in children with the typical physical appearance of this syndrome regardless of age since medullary carcinoma of the thyroid gland appears in almost every case. Calcitonin, a hormone secreted by the C-cells, serves as a plasma tumor marker. Intravenously administered, pentagastrin is a potent secretagogue which is very useful in the early diagnosis of either primary or recurrent medullary carcinoma. With this pentagastrin test, a laboratory screening program is possible allowing the clinician, specialist, to recognize the syndrome.

Biomarkers, Tumor↗
PubMed1992

New insights into the clinical features, pathogenesis and molecular genetics of Huntington disease.

Traditionally, a clinical diagnosis of Huntington disease (HD) presents no problems in patients with a positive family history, consistent with autosomal dominant inheritance, chorea or other extrapyramidal motor signs, and progressive mental decline. However, due to the slowly progressive nature of the disease and the slow evolution of signs and symptoms, it is often difficult to determine when at risk individuals are showing early signs. Moreover, the clinical recognition of both early and late-onset cases, and of choreic patients in whom a family history is lacking, presents special diagnostic challenges. In recent years, much progress has been made in the recognition of early clinical signs of the disease. Factors which have contributed to this understanding include the longitudinal study of large cohorts of at-risk individuals, particularly in Venezuela, the data from predictive testing programs, and the application of positron emission tomography (PET)-scanning to individuals without overt chorea. We are now able to identify persons at risk as being affected before they display overt and obvious involuntary movements.

Adolescent↗
PubMed1992

Multicenter evaluation of the novel ABN Western blot (immunoblot) system in comparison with an enzyme-linked immunosorbent assay and a different Western blot.

A new, modular Western blot (immunoblot) system for human immunodeficiency virus (HIV) antibodies (ABN WesPage; Wellcome) was compared with enzyme immunoassays (Wellcome, Behringwerke, and Abbott) and with a U.S. Food and Drug Administration (FDA)-licensed Western blot (DuPont) in a multicenter study. A total of 649 serum samples from HIV patients at different stages of the disease, as well as from high-risk patients, from patients with conditions unrelated to AIDS, and from healthy blood donors, were used in the evaluation along with nine seroconversion panels. For evaluation of Western blot reactivity, both Centers for Disease Control (CDC) and FDA criteria were used. With the DuPont Western blot as the reference assay, the overall sensitivity and specificity of the ABN WesPage were 100 and 99.1%, respectively, when indeterminate results were not taken into account and when both tests were interpreted in accordance with CDC criteria. The DuPont Western blot detected significantly more antibodies to pol and gag gene products than the ABN WesPage. The ABN WesPage showed a higher positive rate of detection of viral envelope band gp160. When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively. When the DuPont Western blot was interpreted in accordance with the manufacturer's instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate. The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.

AIDS Serodiagnosis↗
PubMed1992

Quantitative assessment of urinary protein and enzyme excretion--a diagnostic programme for the detection of renal involvement in type I diabetes mellitus.

In an effort to establish a reliable programme for the clinical monitoring of renal involvement in patients with type-I diabetes mellitus, we quantified the urinary excretion of immunoglobulin G (IgG), transferrin (Tf), albumin (Alb), alpha 1-microglobulin (alpha 1MG), N-acetyl-beta-D-glucosaminidase (NAG), and total protein in 130 dipstick negative children and young adults with type-I diabetes. Eighty-five sex- and age-matched healthy persons served as a control group for the definition of the upper reference limits (95th centiles; micrograms min-1 1.73 m2): transferrin 1.4; albumin 16.6; total protein 27.1; NAG: 2.0 mU min-1 1.73 m2. Sex-related differences were detected for IgG (men: 3.8; women: 1.7) and alpha 1 MG (men: 6.0; women: 4.0 micrograms min-1 1.73 m2). The urinary excretion of IgG, Tf, alpha 1MG, NAG, and total protein was significantly higher in subjects with diabetes when compared to healthy controls (p < 0.01). Furthermore, 20 patients (15%) showed an elevated excretion of tubular markers (alpha 1MG and NAG), and 3 patients (2%) of at least two glomerular markers (Alb and/or Tf and/or IgG). Additionally, 18 individuals (14%) presented a mixed excretion pattern of both tubular and glomerular markers. These data suggest that the quantitation of both glomerular and tubular proteinuria provides a sensitive and cost-effective instrument for the non-invasive screening for renal involvement in patients with diabetes mellitus.

Adolescent↗