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Biomedical subjects

B Baker

Publications and source records attributed to B Baker.

At least 73 records · Page 4Linked to original sources
PubMed1994

Identification of a novel HIV-1 TAR RNA bulge binding protein.

The Tat protein binds to TAR RNA to stimulate the expression of the human immunodeficiency virus type 1 (HIV-1) genome. Tat is an 86 amino acid protein that contains a short region of basic residues (aa49-aa57) that are required for RNA binding and TAR is a 59 nucleotide stem-loop with a tripyrimidine bulge in the upper stem. TAR is located at the 5' end of all viral RNAs. In vitro, Tat specifically interacts with TAR by recognising the sequence of the bulge and upper stem, with no requirement for the loop. However, in vivo the loop sequence is critical for activation, implying a requirement for accessory cellular TAR RNA binding factors. A number of TAR binding cellular factors have been identified in cell extracts and various models for the function of these factors have been suggested, including roles as coactivators and inhibitors. We have now identified a novel 38 kD cellular factor that has little general, single-stranded or double-stranded RNA binding activity, but that specifically recognises the bulge and upper stem region of TAR. The protein, referred to as BBP (bulge binding protein), is conserved in mammalian and amphibian cells and in Schizosaccharomyces pombe but is not found in Saccharomyces cerevisiae. BBP is an effective competitive inhibitor of Tat binding to TAR in vitro. Our data suggest that the bulge-stem recognition motif in TAR is used to mediate cellular factor/RNA interactions and indicates that Tat action might be inhibited by such competing reactions in vivo.

Animals↗
PubMed1994

Perceived interpersonal attitudes and psychiatric complaints in patients with essential hypertension.

The association between perceived interpersonal attitudes and psychiatric complaints in a group of hypertensives (N = 37) was evaluated. The Influential Relationships Questionnaire (IRQ), which measures perceived care, overprotection, and criticism, was administered to all patients. Hypertensives with psychiatric complaints (n = 14) were not different in terms of age, gender, obesity, smoking, alcohol intake, occupational stress, drug treatment, and baseline systolic and diastolic blood pressures compared to hypertensives without psychiatric complaints. They were, however, different in perceiving their social environment. Hypertensives with psychiatric complaints perceived their social environment as less caring, more overprotective, and more critical. Finally, patients without psychiatric complaints showed better outcome in terms of baseline vs. follow-up measures of systolic and diastolic blood pressures than did patients without psychiatric complaints.

Adolescent↗
PubMed1994

Seroprevalence of hepatitis B and C in a Merseyside hospital for the mentally handicapped.

This study reports the prevalence of antibodies to hepatitis B virus (HBV) and C virus (HCV), and the frequency of potential exposure to these viruses among patients and staff in six long-stay wards of a hospital caring for mentally handicapped adults from the Mersey region. A retrospective survey of risk behaviour among 134 patients and questionnaire survey of 75 nursing staff was performed. Serum samples from both groups were tested for HBV markers and patient sera for antibodies to HCV by enzyme-linked immunosorbent assay (ELISA). None of the 102 patients tested had antibodies against HCV, although 17 had detectable antibody to HBV core (anti-HBc). Seven out of the 17 were positive for HBV surface antigen. None was positive for IgM antibody to HBV core. Only 1 out of 61 staff had anti-HBc and none was positive for surface antigen. Twenty-nine of 75 (39%) staff reported bites sufficient to break the skin and 52 (69%) significant other injuries from patients; 25 (31%) of staff had not received HBV vaccination. None of the patients had received HBV vaccine. We conclude that HCV does not appear to be a major hazard in this closed community but the prevalence of HBV markers indicating past exposure among patients is high, vaccine uptake is incomplete and incidents which may allow viral transmission are frequent.

Adult↗
PubMed1994

Insulin-like growth factor axis abnormalities in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. To assess whether patients with BPH have alterations in their prostatic IGF axis, we measured the expression (by Northern blotting) and the production (by Western ligand blotting and RIA) of insulin-like growth factor-II (IGF-II) and IGF-binding proteins (IGFBPs) in prostatic epithelial and stromal cell strains grown from normal (n = 7), hyperplastic (n = 7), and malignant (n = 5) surgical specimens. Levels of IGF-II messenger ribonucleic acid (mRNA; normalized for actin expression) were 10-fold higher in BPH stromal cell strains compared to those in normal stromal cell strains (P < 0.0001). Western ligand blotting of conditioned medium (CM) from normal stromal cells demonstrated the presence of IGFBP-2, -3, and -4. In the CM of BPH stromal cells, IGFBP-2 levels were dramatically reduced to less than 20% of normal (P < 0.001). Additionally, IGFBP-5, which was not observed in significant amounts in normal stromal cell-CM, was found in large quantities in BPH stromal cell-CM. Northern blot analysis of mRNA from normal and BPH stromal cells demonstrated a 5-fold decrease in IGFBP-2 mRNA (P < 0.001) and a 4-fold increase in IGFBP-5 mRNA (P < 0.01) in BPH compared to normal cells. In prostate stromal cells from cancer specimens, no abnormalities were found. No abnormalities were observed in the IGF axis parameters evaluated in prostate epithelial cells from BPH or cancer strains. We conclude that prostatic stromal cell strains isolated from patients with BPH hyperexpress the mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA. IGFBP, but not IGF-II, peptide levels in CM correspond to the mRNA differences. This is the first documentation of altered gene and protein expression in this common disease. We speculate that these abnormalities in the IGF axis may be important in the pathogenesis of BPH.

Blotting, Northern↗
PubMed1993

Binding of myotoxin a to cultured muscle cells.

The binding of radiolabeled myotoxin a to various cultured cell lines was evaluated. One rat skeletal muscle-derived cell line, L8, bound substantially more myotoxin a than did all all other cell lines examined. Several biophysical parameters of myotoxin a-L8 binding were determined. Binding was saturable with a moderate binding affinity. Scatchard analysis and Hill plots indicated a single class of binding sites. The binding was reversible, as demonstrated by chase experiments. Radiolabeled myotoxin a bound to the cell surface at a site inaccessible to the general protease, pronase. Specificity and biological relevance of the binding was suggested by competition with unlabeled toxin and various peptides derived from the toxin. Biologically active peptides, corresponding to the N- and C-terminal sequence of myotoxin a, competed with radiolabeled toxin for L8 binding. It was concluded that the L8 system is a suitable cell model to study myotoxin a mechanism of action.

Amino Acid Sequence↗
PubMed1993

Linked and unlinked transposition of a genetically marked Dissociation element in transgenic tomato.

We have introduced a genetically marked Dissociation transposable element (Dsneo) into tomato. In the presence of Ac transposase, Dsneo excised from an integrated T-DNA and reinserted at numerous new sites in the tomato genome. The marker genes of Dsneo (NPTII) and the T-DNA (HPT) facilitated identification of plants bearing transposon excisions and insertions. To explore the feasibility of gene tagging strategies in tomato using Dsneo, we examined the genomic distribution of Dsneo receptor sites, relative to the location of the donor T-DNA locus. Restriction fragment length polymorphism mapping of transposed Dsneo elements was conducted in two tomato families, derived from independent primary transformants each bearing Dsneo within a T-DNA at a unique position in the genome. Transposition of Dsneo generated clusters of insertions that were positioned on several different tomato chromosomes. Dsneo insertions were often located on the same chromosome as the T-DNA donor site. However, no insertion showed tight linkage to the T-DNA. We consider the frequency and distance of Dsneo transposition observed in tomato to be well suited for transposon mutagenesis. Our study made use of a novel, stable allele of Ac (Ac3) that we discovered in transgenic tomato. We determined that the Ac3 element bears a deletion of the outermost 5 base pairs of the 5'-terminal inverted repeat. Though incapable of transposition itself, Ac3 retained the ability to mobilize Dsneo. We conclude that a dual element system, composed of the stable Ac3 trans-activator in combination with Dsneo, is an effective tool for transposon tagging experiments in tomato.

Alleles↗
PubMed1993

Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum.

IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38-kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (alpha) subunit in a high-molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25-55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 +/- 2.2 versus 10.1 +/- 2.1 micrograms/mL). High-MW (150-kD) fractions of CRF and normal sera, obtained by neutral size-exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [125I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38-kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Psychiatric assessment of patients with life-threatening cardiac arrhythmias.

OBJECTIVE: This article describes the development of a protocol specifically designed for the psychiatric assessment of patients with life-threatening ventricular arrhythmias. METHOD: Psychiatric assessment occurs in the context of a team approach in which the cardiologist has a pivotal role. Initial findings and one-year follow-up data on the first twenty-five patients evaluated psychiatrically are presented. RESULTS: Findings tend to confirm that psychiatric complaints are common on initial assessment and suggest that patients with life-threatening ventricular arrhythmias who do not use the psychological mechanism of denial and volunteer psychological complaints may constitute a subgroup of patients who would be more amenable to psychiatric intervention compared to those denying psychological complaints at initial psychiatric interview. CONCLUSION: Psychiatrists and associated professionals should become more involved with patients with life-threatening cardiac arrhythmias.

Adaptation, Psychological↗
PubMed1993

A randomized, controlled trial of recombinant alpha-interferon therapy for chronic hepatitis B.

OBJECTIVES: To evaluate the effect of recombinant alpha-interferon in chronic hepatitis B. METHODS: Patients were stratified at entry according to their serum aspartate aminotransferase (AST) values, randomized to receive alpha-interferon (alfa-2b, 10 million units three times weekly) or to be untreated controls for 16 wk. Effect of therapy on levels of hepatitis B viral (HBV) DNA and aminotransferase activities in serum and hepatitis B e antigen (HBeAg) status was monitored. RESULTS: Forty-seven patients entered the trial; 11 of 25 (44%) patients receiving interferon responded by clearing HBeAg and HBV DNA within 6 months, compared to one of 22 (5%) controls (p < 0.05). Among those with serum AST values < 100 U/L, 33% responded and among those with AST values > 100 U/L, 60% responded. Within the 6-month study period, 36% of treated patients had normal serum alanine aminotransferase (ALT) values, and 16% had cleared hepatitis B surface antigen (HBsAg) from serum, whereas none of the controls had normal ALT values or had lost HBsAg. Interferon was stopped early in three patients (6.5%), and dosage was reduced in a further 16 patients (35%) because of adverse effects. Predictive factors for a response were the pretreatment serum ALT and AST activities. CONCLUSIONS: alpha-Interferon therapy (three times weekly) is relatively well tolerated and is effective in clearing HBeAg and HBV DNA in approximately one-third of treated patients.

Adult↗
PubMed1992

Structure-function relationship of myotoxin a using peptide fragments.

Myotoxin a, a small basic polypeptide isolated from the venom of prairie rattlesnake (Crotalus viridis viridis), has been shown to bind to sarcoplasmic reticulum (SR) Ca(2+)-ATPase. The attachment of myotoxin a to Ca(2+)-ATPase is believed to cause uncoupling of the calcium pump. In order to further elucidate which portion of myotoxin a is important for the uncoupling action, five peptides were synthesized and two peptide fragments were obtained by chemical cleavage. These peptides correspond to discrete portions of the primary sequence of myotoxin a. The peptides are equivalent to the primary sequence of myotoxin a from 1 to 16 residues, 7 to 22 residues, 13 to 28 residues, 19 to 34 residues, and 25 to 42 residues. Chemically produced fragments are equivalent to 1 to 28 residues and 29 to 42 residues of myotoxin a. Peptides of the sequences "YKQCHKKGGHCFPKEK" and "LGKMDCRWKWKCCKKGSG" of myotoxin a inhibited 45Ca uptake into isolated SR and bound to Ca(2+)-ATPase. The same peptides caused weak skeletal muscle vacuolization similar to that caused by native myotoxin a and increased serum creatine kinase activity. The active peptides correspond to the N-terminal and C-terminal portions of myotoxin a. The inactive or less active peptides have sequences which correspond to the middle sequence of myotoxin a. From this study, both the N-terminal and the C-terminal regions of primary sequence of myotoxin a are required to express myotoxin a's biological activity.

Amino Acid Sequence↗
PubMed1992

Medical management of inflammatory bowel disease in a spider monkey.

Inflammatory bowel disease was diagnosed in a 3-year-old, captive-born, hand-raised, female spider monkey (Ateles geoffroyi). The diagnosis was based on clinical signs, positive-contrast radiographic series, endoscopy, histologic appearance of intestinal biopsy specimens, and the monkey's response to treatment. Treatment consisted of oral administration of prednisone, sulfasalazine, and trimethoprim-sulfamethoxazole. Supportive care included a bland diet and an electrolyte solution given free choice. Although several infective agents were considered, this case illustrates that recurrent enteritis in primates may be noninfectious and may respond to anti-inflammatory agents.

Animals↗
PubMed1992

Expression of interferon-gamma receptors in normal and psoriatic skin.

Psoriatic keratinocytes have a reduced antiproliferative response to interferon (IFN)-gamma, and HLA-DR expression is usually not observed on keratinocytes in psoriatic plaques despite the presence of activated T cells. We have therefore compared the expression of IFN-gamma receptors in psoriatic skin with that of normal human skin. Using mouse monoclonal antibodies and immunoperoxidase staining on cryostat cut sections, we detected IFN-gamma receptors on keratinocytes throughout the epidermal layers except stratum corneum in normal skin (n = 11). Biopsy specimens from involved psoriatic skin (n = 17) consistently showed a staining pattern that differed from that of normal skin in that only the lower part of epidermis reacted with the antibodies to IFN-gamma receptors, whereas the upper layers showed no or minimal staining. Expression of IFN-gamma receptors in uninvolved psoriatic skin (n = 16) did not differ from that of healthy controls. Forty-five percent of the biopsies from lesional psoriatic skin displayed ICAM-1 positive keratinocytes, and only two specimens had a limited expression of HLA-DR reactive keratinocytes. The decreased binding of antibodies against the IFN-gamma receptors in the upper part of psoriatic epidermis might be secondary to abnormal maturation of psoriatic keratinocytes or a primary defect involving abnormal modulation of IFN-gamma receptors.

Adult↗
PubMed1991

Binding of myotoxin a to sarcoplasmic reticulum Ca(2+)-ATPase: a structural study.

The interaction of myotoxin alpha with intact sarcoplasmic reticulum (SR) components was investigated, and two SR proteins were identified that associated with myotoxin a. One of the proteins has an apparent molecular weight similar to the Ca(2+)-ATPase, the major SR protein responsible for calcium loading. Ca(2+)-ATPase was purified, and its interaction with myotoxin a was studied. Evidence for specific binding of myotoxin a to Ca(2+)-ATPase was established by isolating chemically cross-linked myotoxin a-Ca(2+)-ATPase complexes and further proving their association with anti-myotoxin a antibodies. The binding region of myotoxin a was further delineated by cleaving the protein with cyanogen bromide (CNBr) into two fragments, a larger N-terminal fragment of 28 residues and a smaller C-terminal fragment of 14 residues. Competition experiments with 125I-myotoxin a showed that the C-terminal fragment competed better against 125I-myotoxin a than the N-terminal fragment for SR protein binding. Two overlapping peptides covering the sequence of the N-terminal fragment were synthesized to clarify the interaction of the N-terminal fragment of myotoxin a with SR proteins. A 16-residue peptide corresponding to residues 1-16 competed strongly with 125I-myotoxin a, while a second peptide (residues 13-28) did not.

Amino Acid Sequence↗
PubMed1991

Long-term remission of chronic hepatitis B after alpha-interferon therapy.

OBJECTIVE: To evaluate whether remissions of chronic hepatitis B induced by alpha-interferon therapy are of long duration. DESIGN: Cohort study. SETTING: Clinical Center of the National Institutes of Health, a tertiary referral center. PATIENTS: Sixty-four patients with chronic hepatitis B were treated with alpha-interferon between 1984 and 1986. MAIN OUTCOME MEASURES: Patients were followed with frequent examinations and determinations of serum liver biochemical tests and hepatitis B virus (HBV) markers including hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA using blot hybridization and polymerase chain reaction. RESULTS: Among 64 patients with chronic hepatitis B who were treated with alpha-interferon, 23 (36%) responded to treatment with loss of HBeAg and improvement in serum aminotransferases. All 23 have been followed for 3 to 7 years (mean, 4.3 years). During follow-up, 3 of 23 patients relapsed, with reappearance of HBeAg and abnormal serum aminotransferases, all within 1 year of therapy. The remaining 20 patients continued to have no detectable HBeAg or HBV DNA (using blot hybridization) in serum and to be asymptomatic for liver disease, although 3 had minimal elevations in serum aminotransferases. Thirteen patients (65%) became negative for HBsAg between 0.2 and 6 years (mean, 3 years) after loss of HBeAg. Although no patient had HBV DNA that was detectable by blot hybridization, the 7 patients who remained HBsAg positive all had HBV DNA in serum detected by polymerase chain reaction, but only 2 of 13 HBsAg-negative patients had viral genome using this method. Testing sequential samples indicated that HBV DNA detected by polymerase chain reaction usually disappeared at or around the time that test results for HBsAg became negative. CONCLUSIONS: Remissions in chronic hepatitis B induced by alpha-interferon are of long duration and are followed, in most patients, by the loss of HBsAg and all evidence of residual virus replication.

Adult↗
PubMed1991

A computer-aided control, design and image-processing system for electron microscopes.

A computer-control system for electron microscopes is described. The aim is to reduce a complex series of vacuum-system controls to a menu-driven program that simplifies the operation of the microscope. The system also incorporates image processing, notebook, computer-aided design, and communication functions. It is designed around a commercially available computer workstation. This system has been implemented on an institute-built photoelectron microscope of ultrahigh-vacuum design.

Computer Graphics↗
PubMed1991

Ac transposition from a T-DNA can generate linked and unlinked clusters of insertions in the tomato genome.

We have investigated the distribution of transposed Acs in the tomato genome. Our approach has been to clone the regions flanking the T-DNAs and transposed Acs from two transgenic lines of tomato and place these sequences on the tomato restriction fragment length polymorphism (RFLP) map. The distribution of transposed Acs around the T-DNA and at locations unlinked to the T-DNA indicates that Ac transposes to linked and unlinked sites in tomato as it does in maize. The structure and terminal sequence of these cloned elements shows that Ac remains intact after transposition. We discuss these results and their bearing on gene tagging strategies using Ac and Ds.

Base Sequence↗