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Biomedical subjects

S Tucker

Publications and source records attributed to S Tucker.

At least 37 records · Page 2Linked to original sources
PubMed1996

Systemic anomalies in 77 patients with congenital anophthalmos or microphthalmos.

Congenital anophthalmos and microphthalmos are rare conditions which can have associated pathology in the second eye and/or systemic anomalies. A retrospective review of 77 patients with congenital anophthalmos or microphthalmos seen at Moorfields Eye Hospital over a 13 year period was performed. A detailed description of the ocular and systemic anomalies present in our series of patients is given, and the current understanding of the pathogenesis of congenital anophthalmos and microphthalmos is reviewed.

Abnormalities, Multiple↗
PubMed1996

Genotypic analysis of primary head and neck squamous carcinoma by combined fluorescence in situ hybridization and DNA flow cytometry.

Concurrent DNA flow cytometric (FCM) and fluorescence in situ hybridization (FISH) analyses were prospectively performed on 24 primary untreated head and neck squamous carcinomas for characterization of the genotypic and phenotypic DNA aberrations of these neoplasms. Eleven tumors (42.0%) manifested DNA diploidy (DI = 1.00) and 15 (58.0%) had DNA aneuploidy (DI < or > 1.00) by FCM. Fluorescence in situ hybridization results showed aneusomy in the majority of DNA diploid and in all DNA aneuploid tumors. The extent of the abnormalities for individual chromosomes and the number of involved chromosomes in a given DNA diploid or aneuploid tumor were significantly different. Overall, a statistical correlation between the FCM DNA index (DI) and the magnitude of the chromosomal aberration by FISH was found. Our results also show a significant association between the DI and histologic differentiation and stage of disease in these neoplasms. In conclusion, (1) chromosomal aneusomy characterizes most DNA diploid (DI = 1.00) and all DNA aneuploid (DI < or > 1.00) head and neck squamous carcinomas; (2) polysomy is the most prevalent finding; (3) loss of the Y chromosome in tumors from male patients is a consistent feature; (4) the FCM DI reflects net chromosomal gains or losses in these neoplasms; and (5) DNA aneuploidy is associated with tumor aggressiveness.

Adult↗
PubMed1996

Inward rectifier potassium channels. Cloning, expression and structure-function studies.

A PCR-based cloning strategy was used to identify novel subunits of the two-transmembrane domain inward rectifier potassium channel family from rat brain, heart, and skeletal muscle. When expressed in Xenopus oocytes, two of these clones (Kir4.1 and Kir2.3) gave rise to inwardly rectifying potassium currents. Two-electrode voltage clamp commands to potentials negative to EK evoked inward potassium-selective currents which rapidly reached a peak amplitude and then relaxed to a steady-state level. Differences in the extent of current relaxation, the degree of rectification, and the voltage-dependent block by external cesium were detected. Two other members of this family (Kir5.1 and Kir3.4) did not produce macroscopic currents, when expressed by themselves, yet both subunits modified the currents when coexpressed with other specific members of the Kir family. Expression of chimeric subunits between Kir4.1 and either Kir5.1 or Kir3.4 suggested that the transmembrane domains determine the specificity of subunit heteropolymerization, while the C-terminal domains contribute to alterations in activation kinetics and rectification. Expression of covalently linked subunits demonstrated that the relative subunit positions, as well as stoichiometry, affect heteromeric channel activity.

Animals↗
PubMed1995

Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit.

The ATP-sensitive K-channel plays a central role in insulin release from pancreatic beta-cells. We report here the cloning of the gene (KCNJ6) encoding a putative subunit of a human ATP-sensitive K-channel expressed in brain and beta-cells, and characterisation of its exon-intron structure. Screening of a somatic cell mapping panel and fluorescent in situ hybridization place the gene on chromosome 21 (21q22.1-22.2). Analysis of single-stranded conformational polymorphisms revealed the presence of two silent polymorphisms (Pro-149: CCG-CCA and Asp-328: GAC-GAT) with similar frequencies in normal and non-insulin-dependent diabetic patients.

Adenosine Triphosphate↗
PubMed1995

The efficacy of parent training for promoting positive parent-toddler relationships.

The effectiveness of a parent training program for promoting positive parent-child relationships was examined among families of 2-year-olds. Forty-six mothers and fathers and their toddlers were assigned to either an intervention or comparison group. Intervention group parents participated in a 10-week program that focused on principles for effectively interacting with their toddlers. Parents completed measures of parenting self-efficacy, depression, stress, and perceptions of their toddler's behaviors and were videotaped playing with their toddlers preintervention, postintervention, and 3 months following the intervention. Repeated measures ANOVAs showed that the parent training program led to significant increases in maternal self-efficacy, decreases in maternal stress, and improvements in the quality of mother-toddler interactions. No significant effects were found among fathers. Explanations for obtaining different outcomes for mothers and fathers are discussed and directions for future research are recommended.

Adult↗
PubMed1995

Western blotting and isoform analysis of cathepsin D from normal and malignant human breast cell lines.

Cathepsin D from normal (Hs578Bst) and malignant (MCF7, MDA-MB-231) breast cell lines has been characterized with regard to its kinetic properties, activity levels, precursor and processed M(r) forms, and isoform composition. Normal cell cathepsin D appears to have a more neutral pH optimum (pH 3.5) than the cancer cell line (pH 3.0-3.2) and greater activity between pH values of 4.0 to 4.5. The two cancer cell lines have approximately 1.5 to 2.0-fold increased total acid protease activity and 2 to 3-fold increased pepstatin-inhibitable protease activity (i.e. cathepsin D) when compared to the normal breast cell line. Western blotting indicates that a major processed form of cathepsin D for all three cell lines occurs at 31 kDa. The cancer cell lines contain significant amounts of cathepsin D precursors of 47 and 42 kDa whereas the normal cell line contains little if any of these precursors. Isoelectric focusing indicates that the normal cell line contains approximately 50% of its total acid protease activity at pIs above 4 whereas the cancer cell lines contain 70-80% of their protease activity at such pIs. In addition, the cancer cell lines contain two to three major isoforms between pIs of 5.5 and 6.3 which were not present in the normal cell line. The isoforms from pI values of 5.5 to 7.3 for all three cell lines are 100% pepstatin-inhibitable. In addition, Western blot analysis indicates that these isoforms contain the processed 31 kDa form of cathepsin D. The combined results indicate that the two breast cancer cell lines are similar to biopsied malignant breast tissue in exhibiting altered acid protease isoform profiles with increased relative amounts of pepstatin-inhibitable and immunoreactive acid protease activity (cathepsin D) compared to normal breast tissue or cells.

Aspartic Acid Endopeptidases↗
PubMed1995

Homologs of the Shigella IpaB and IpaC invasins are required for Salmonella typhimurium entry into cultured epithelial cells.

Entry into host cells is an essential feature in the pathogenicity of Salmonella spp. The inv locus of Salmonella typhimurium encodes several proteins which are components of a type III protein secretion system required for these organisms to gain access to host cells. We report here the identification of several proteins whose secretion into the culture supernatant of S. typhimurium is dependent on the function of the inv-encoded translocation apparatus. Nucleotide sequence analysis of the genes encoding two of these secreted proteins, SipB and SipC, indicated that they are homologous to the Shigella sp. invasins IpaB and IpaC, respectively. An additional gene was identified, sicA, which encodes a protein homologous to IpgC, a Shigella protein that serves as a molecular chaperone for the invasins IpaB and IpaC. Nonpolar mutations in sicA, sipB, and sipC rendered S. typhimurium unable to enter cultured epithelial cells, indicating that these genes are required for bacterial internalization.

Amino Acid Sequence↗
PubMed1995

Risk classification for large cell lymphoma using lactate dehydrogenase, beta-2 microglobulin, and thymidine kinase.

We have previously proposed a staging system for large cell lymphoma using the two serum markers beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH). We recently tested this model in a different cohort of patients with large cell lymphoma and also examined the possible contribution of thymidine kinase (TK), a previously reported serologic prognostic factor. Using an inclusion criteria in the multivariate analysis for both forward and backward selection of p < 0.15, only LDH, B2M, and TK were significant independent prognostic factors for both time to treatment failure (TTF) and survival. Inclusion of TK in the serologic model resulted in three significantly different risk groups for both TTF and survival. Corresponding endpoints at three years were: 1) good risk (no markers elevated, n = 43): 78%, 91%; 2) intermediate risk (1 or 2 markers elevated, n = 47): 41%, 36%; 3) poor risk (3 markers elevated, n = 11): 0%, 0%. This analysis extends the observation of the independent prognostic significance of B2M and LDH. The addition of TK permits a more precise estimate of risk, contributing to the utility of a serological staging system for large cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Let's go to the gym].

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Western blotting and enzymatic activity analysis of cathepsin D in breast tissue and sera of patients with breast cancer and benign breast disease and of normal controls.

Increased total antigen amounts of cathepsin D in breast tissue have been reported to be associated with increased disease recurrence, more frequent metastasis, and increased mortality in breast cancer patients. In the present study, Western blotting analysis has been used for the first time to determine the relative amounts of precursor and processed forms of cathepsin D in sera and breast tissue of patients with breast cancer, benign breast disease, and normal controls. Sera gave similar blots for breast cancer patients and controls with two major forms of cathepsin D (M(r) 52,000 and 27,000). Malignant breast tissue contained the two forms of cathepsin D found in sera and an additional M(r) 31,000 form which was found in significantly increased (P < 0.001) relative amounts in breast tissue from 43 breast cancer patients [24 +/- 12% (SD)] when compared to 51 benign breast disease patients (13 +/- 8.9%) and 23 normal controls (1.8 +/- 4.4%). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.41) in relative amounts of the M(r) 31,000 form of cathepsin D between proliferative-type and non-proliferative-type fibrocystic breast disease. A cathepsin D assay has been optimized for human breast tissue and used to demonstrate for the first time significantly increased (P < 0.001) amounts of pepstatin-inhibitable, cathepsin D-specific activity in breast tissue from 36 breast cancer patients (2.2 +/- 1.4 units/mg of protein) when compared to 47 benign breast disease patients (0.63 +/- 0.43) and 23 normal controls (0.24 +/- 0.21). Preliminary analysis of subgroups of benign breast disease patients suggested no significant difference (P = 0.21) in pepstatin-inhibitable, cathepsin D-specific activity between proliferative-type and nonproliferative-type fibrocystic breast disease. The positive correlation (r = 0.82) of increased amounts of the M(r) 31,000 form of cathepsin D and increased pepstatin-inhibitable, cathepsin D enzymatic activity in malignant breast tissue suggests that the M(r) 31,000 form is the proteolytically active form of the enzyme which may be involved in the development and/or metastatic spread of breast cancer.

Adult↗
PubMed1994

A survey of actinic keratoses among paraquat production workers and a nonexposed friend reference group.

Follow-up on two reports of an excess of keratoses among paraquat production workers was conducted to evaluate the contribution of occupational exposures to the prevalence of keratoses among workers in a paraquat production plant in Texas. A cross-sectional study design was used to compare the prevalence of keratoses among current workers to an age, race, and sex frequency-matched group of their friends who had never worked at the plant. The analysis is based on 112 workers and 232 friends. Exposure, outcome, and covariables used in the analyses were obtained from an interview questionnaire, dermatology exam, and company records. Overall, the prevalence proportion of the presence of any actinic keratoses among workers and friends was similar (0.30 and 0.28, respectively). Among high cumulative exposed workers, the prevalence of any actinic keratoses was 0.40 compared to 0.20 among low-exposed workers and 0.28 among friends. These results were further explored using a multiple logistic regression approach to adjust for known risk and possibly confounding variables. Statistically significant high risks of actinic keratoses were demonstrated for freckling before age 16 years, older age, suntanning behaviors, occupational exposure to polycyclic aromatic hydrocarbons (PAH), and Fitzpatrick skin type. There was no significant contribution of overall exposure status (worker vs. friend). Similar to the crude analysis, the odds of actinic keratoses of high-exposed workers compared to friends was 1.9 (confidence interval [CI] = 0.9-4.2) whereas the comparable odds ratio for low-exposed workers vs. friends was 0.6 (CI = 0.2-1.7). These data do not demonstrate an excess of actinic keratoses overall nor any consistent increase in the odds of keratoses with an increase in plant exposure level.

Adult↗
PubMed1994

Inhibition by all-trans-retinoic acid of tumor necrosis factor and nitric oxide production by peritoneal macrophages.

Besides their growth-inhibiting and differentiation-inducing properties, retinoids have been shown to exert immunomodulatory and anti-inflammatory functions by mechanisms that are not well understood. Tumor necrosis factor-alpha (TNF), a cytokine produced by mononuclear phagocytes, has been shown to be an important mediator of endotoxin-induced septic shock, cachexia, bone resorption, and inflammation. Nitric oxide may also have a role in septic shock, hypotension, and vasodilatation. In this study, we examined the effects of retinoids on the production of TNF and nitric oxide by murine peritoneal macrophages. Of the various retinoids studied, all-trans-retinoic acid (RA) was most potent; it almost completely inhibited the production of TNF by macrophages activated with endotoxin and interferon-gamma. The inhibitory effect was dependent on the dose and duration of RA exposure to macrophages. RA also blocked phorbol ester-induced TNF production in a macrophage cell line (RAW 264.7). Besides TNF, the retinoid suppressed the production of nitric oxide from activated peritoneal macrophages. The importance of these results in relation to controlling various harmful effects of cytokines released by activated macrophages is discussed.

Animals↗
PubMed1994

A glycosylphosphatidylinositol (GPI)-negative phenotype produced in Leishmania major by GPI phospholipase C from Trypanosoma brucei: topography of two GPI pathways.

The major surface macromolecules of the protozoan parasite Leishmania major, gp63 (a metalloprotease), and lipophosphoglycan (a polysaccharide), are glycosylphosphatidylinositol (GPI) anchored. We expressed a cytoplasmic glycosylphosphatidylinositol phospholipase C (GPI-PLC) in L. major in order to examine the topography of the protein-GPI and polysaccharide-GPI pathways. In L. major cells expressing GPI-PLC, cell-associated gp63 could not be detected in immunoblots. Pulse-chase analysis revealed that gp63 was secreted into the culture medium with a half-time of 5.5 h. Secreted gp63 lacked anti-cross reacting determinant epitopes, and was not metabolically labeled with [3H]ethanolamine, indicating that it never received a GPI anchor. Further, the quantity of putative protein-GPI intermediates decreased approximately 10-fold. In striking contrast, lipophosphoglycan levels were unaltered. However, GPI-PLC cleaved polysaccharide-GPI intermediates (glycoinositol phospholipids) in vitro. Thus, reactions specific to the polysaccharide-GPI pathway are compartmentalized in vivo within the endoplasmic reticulum, thereby sequestering polysaccharide-GPI intermediates from GPI-PLC cleavage. On the contrary, protein-GPI synthesis at least up to production of Man(1 alpha 6)Man(1 alpha 4)GlcN-(1 alpha 6)-myo-inositol-1-phospholipid is cytosolic. To our knowledge this represents the first use of a catabolic enzyme in vivo to elucidate the topography of biosynthetic pathways. GPI-PLC causes a protein-GPI-negative phenotype in L. major, even when genes for GPI biosynthesis are functional. This phenotype is remarkably similar to that of some GPI mutants of mammalian cells: implications for paroxysmal nocturnal hemoglobinuria and Thy-1-negative T-lymphoma are discussed.

Animals↗
PubMed1994

Parenting confidence during toddlerhood. A comparison of mothers and fathers.

Previous research has shown the Toddler Care Questionnaire (TCQ) to be a valid measure of parenting confidence among mothers of toddlers. However, there is no evidence demonstrating the validity of the TCQ among fathers of toddlers. The purposes of this study were to 1) examine the reliability and validity of the TCQ among fathers of 12- to 36-month old children and 2) compare the childrearing topics mothers and fathers identify as those for which they would like information. Forty-six married mothers and fathers (n = 92) completed the TCQ, three measures of child behavior, and a measure of parental depression. Maternal confidence was related to depression and all measures of child behavior. Paternal confidence was related only to the intensity of the child's behavior. Mothers requested more than twice the amount of childrearing information than did fathers although there were similarities in the types of information requested. The data support the validity of the TCQ and its clinical utility among fathers of toddlers although different factors appear to affect parenting confidence among mothers and fathers.

Adult↗
PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗
PubMed1994

GPI phospholipase C from Trypanosoma brucei causes a GPI-negative phenotype in Leishmania major: I. Implications for GPI-negative mammalian cells; II. Compartmentalization of two GPI biosynthetic pathways.

The major surface macromolecules of the protozoan parasite Leishmania major, gp63 (a metalloprotease), and lipophosphoglycan (a polysaccharide) are glycosylphosphatidylinositol (GPI)-anchored. We expressed a cytoplasmic glycosylphosphatidylinositol phospholipase C (GPIPLC) in L. major in order to examine the topography of the protein-GPI and polysaccharide-GPI pathways. In L. major cells expressing GPIPLC cell-associated gp63 could not be detected in immunoblots. gp63 was secreted into the culture medium without ever receiving a GPI anchor. Putative protein-GPI intermediates LP-1 and LP-2 decreased about 10-fold. In striking contrast, lipophosphoglycan levels were unaltered. We conclude that reactions specific to the polysaccharide-GPI pathway are compartmentalized within the endoplasmic reticulum, thereby sequestering those intermediates from GPIPLC cleavage. Protein-GPI synthesis, at least up to production of Man(1 alpha 6)Man(1 alpha 4)GlcN(1 alpha 6)-myo-inositol-1-phospholipid, is cytosolic. To our knowledge, this represents the first use of a catabolic enzyme, in vivo, to elucidate the topography of biosynthetic pathways. Intriguingly, the phenotype of GPIPLC-expressing L. major, secretion of proteins with GPI addition signals, and depletion of protein-GPI anchor precursors, is similar to that of some protein-GPI mutants in higher eukaryotes. These findings have implications for paroxysmal nocturnal hemoglobinuria and Thy-1-negative T-lymphoma.

Animals↗
PubMed1993

Complete genomic sequence of the human retinoblastoma susceptibility gene.

A 180,388-bp contig encompassing the human retinoblastoma gene was sequenced in its entirety. Partial analysis of the sequence revealed (1) a high (A+T)/(G+C) ratio and a high density of Line-1 (L1) repeat sequences, suggesting that the locus maps to G-bands 13q14.12 or 13q14.2; (2) Alu repeats that are asymmetrically oriented over a region extending 87 kb; (3) an overabundance of non-Alu-associated poly(A) tracts 10 bp or larger oriented in the antisense rather than the sense direction (36 vs 6); (4) an Alu sequence nested within an L1 repeat, indicating that the expansion of L1 repeats predates at least some of the Alu expansions; (5) at least three newly discovered microsatellite polymorphisms, one of which was subsequently found to be identical to a polymorphism in a microsatellite-based linkage map of the human genome published by another group; and (6) the basis of previously discovered intragenic RFLPs. This sequence should enhance studies of this locus and of the organization of the human genome.

Base Sequence↗