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B Baker

Publications and source records attributed to B Baker.

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

The effect of growth hormone treatment on the insulin-like growth factor axis in a child with nonislet cell tumor hypoglycemia.

We have previously described a case of tumor-associated hypoglycemia secondary to the production of high molecular weight insulin-line growth factor (IGF)-II in a child with congenital neuroblastoma. The child's hypoglycemia resolved with GH therapy and has continued to be well controlled for 1 yr. This represents one of the first cases of nonislet cell tumor hypoglycemia (NICTH) treated successfully with long-term exogenous GH. We now present an in-depth analysis of the IGF axis in this patient, before and after GH treatment. Although IGF-II levels at presentation were in the normal range, they were inappropriate for the patient's low GH state. Furthermore, the percentage of "big" IGF-II was elevated, as was the level of the IGF-IIE peptide, which is normally cleaved in the processing of the mature peptide. On the initial evaluation, GH levels failed to rise in response to hypoglycemia, IGF-I levels were low, IGF binding protein-3 (IGFBP-3) levels were suppressed, and IGFBP-2 levels were elevated. We have shown that baseline IGFBP-3 levels were low by RIA and immunoblotting and have demonstrated that this decrease was not associated with IGFBP protease activity. We have also demonstrated the baseline suppression of the acid labile subunit (ALS) of the 150K ternary complex by a novel immunoblot assay. The ratio of IGFs to IGFBP-3 was dramatically elevated, presumably leading to hypoglycemia. Furthermore, the percentage of serum IGF-I and IGF-II present as part of a binary (50K) complex with IGFBPs was also increased. GH therapy resulted in a normalization of the levels of blood sugars, IGFBP-3, ALS, IGFBP-2, and IGF-I, as well as the IGF/IGFBP-3 ratio. In summary, we have presented evidence that the hypoglycemia in this patient resulted from tumor production of high molecular weight IGF-II, which suppressed GH secretion, leading to the described derangements in the IGF binding proteins. We speculate that as a result of the decreased IGFBP-3 and ALS levels, the IGF population was shifted from the stable 150K complex to lower molecular weight complexes with IGF binding proteins, increasing IGF availability to tissues due to rapid turnover of these low molecular weight complexes. We demonstrated the reversal of the abnormalities in the IGFBP levels with GH treatment, corresponding to the clinical response of euglycemia.

Adenoma, Islet Cell↗
PubMed1996

Serum insulin-like growth factor II levels in normal adolescents and those with insulin dependent diabetes mellitus.

OBJECTIVE: Unlike IGF-I and its principal binding proteins, data regarding IGF-II levels have not been well defined in normal subjects and those with insulin-dependent diabetes mellitus (IDDM). We have therefore measured IGF-II, as well as IGF-I, and IGFBP-3, levels in a large cohort of subjects with IDDM and in age/sex matched controls. PATIENTS: One hundred and fourteen patients with IDDM (57 males, 57 females) and 89 control subjects (49 males, 40 females). MEASUREMENTS: Random blood samples were obtained from each subject for the measurement of IGF-II, IGF-I and IGFBP-3 levels. RESULTS: Mean values of IGF-II (+/- SEM) were 630 (+/- 27.8) micrograms/l and 646 (+/- 32.3) micrograms/l in female and male controls, compared to 569 (+/- 23.3) micrograms/l and 623.3 (+/- 28.1) micrograms/l in female and male diabetics respectively. IGF-II levels did not differ significantly between the sexes or show any change with transition through puberty in either control or diabetic groups. In contrast, IGF-I levels increased through puberty peaking at stages 3-5 in controls (P < 0.001) and G4-5 (P = 0.002) in diabetic males but not females. IGF-I levels in all diabetics were generally lower than in controls, differences reaching significance at G4-5 in males (P = 0.002) and B5 in females (P = 0.002). IGFBP-3 levels did not show any variation with puberty stage in diabetics, in contrast to controls where levels increased, peaking at G4-5 in males (P = 0.001) and B3 in females. IGFBP-3 levels were lower in diabetics of both sexes and at all stages compared to controls (P range 0.047 to < 0.001). Multiple regression analysis revealed significant correlations between IGF-II and IGFBP-3 (F = 20.1, P = < 0.001) and reaffirmed previously observed associations for IGF-I and IGFBP-3. The sum of IGF-I and IGF-II (expressed as nmol/l) correlated with IGFBP-3; r = 0.47 in controls and 0.60 in diabetics. CONCLUSIONS: Insulin-dependent diabetes mellitus is not associated with any significant changes in IGF-II levels during puberty. The binding of IGFBP-3 for both IGF-I and IGF-II is unaltered by insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1995

Transposon tagging of tobacco mosaic virus resistance gene N: its possible role in the TMV-N-mediated signal transduction pathway.

Plants can recognize and resist invading pathogens by signaling the induction of rapid defense responses. Often these responses are mediated by single dominant resistance genes (R genes). The products of R genes have been postulated to recognize the pathogen and trigger rapid host defense responses. Here we describe isolation of the classical resistance gene N of tobacco that mediates resistance to the well-characterized pathogen tobacco mosaic virus (TMV). The N gene was isolated by transposon tagging using the maize Activator (Ac) transposon. We confirmed isolation of the N gene by complementation of the TMV-sensitive phenotype with a genomic DNA fragment. Sequence analysis of the N gene shows that it encodes a protein with an amino-terminal domain similar to that of the cytoplasmic domains of the Drosophila Toll protein and the interleukin 1 receptor in mammals, a putative nucleotide-binding site and 14 imperfect leucine-rich repeats. The presence of these functional domains in the predicted N gene product is consistent with the hypothesis that the N resistance gene functions in a signal transduction pathway. Similarities of N to Toll and the interleukin 1 receptor suggest a similar signaling mechanism leading to rapid gene induction and TMV resistance.

Amino Acid Sequence↗
PubMed1995

Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms' tumour from a BWS patient.

A patient with Beckwith-Wiedemann syndrome (BWS) presented with Wilms' tumour. Examination of the nephrectomy specimen showed, in addition to the tumour, the presence of nephrogenic rests. Nephrogenic rests are thought to be precursor lesions from which a Wilms' tumour may develop. A molecular analysis examining the loss of constitutional heterozygosity (LOCH), initially for chromosome 11, was performed on peripheral blood, the normal kidney, nephrogenic rest and tumour material. The study was extended to include markers from all 23 chromosomes. At each informative, locus, LOCH of the maternal allele was shown in the nephrogenic rest and tumour material. In addition, the normal kidney displayed allele imbalance. It would appear from these results that either extensive LOCH across the genome was an early genetic event in the development of malignancy in this patient or that the tumour and rest developed from cells containing no maternal chromosomes. The apparent LOCH seen in the normal kidney sample implies that full reduction to homozygosity is consistent with a histologically normal appearance. Putative mechanisms to explain this phenomenon are discussed.

Alleles↗
PubMed1995

Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases.

Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients. Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis. Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category II or III disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients. These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1995

Movers and shakers: maize transposons as tools for analyzing other plant genomes.

Transposons have been successfully exploited as insertional mutagens for the efficient identification and isolation of genes (transposon tagging) in many organisms. Plants are no exception. The maize Activator and Suppressor-mutator transposons function when transferred into heterologous plant species, and many different gene tagging systems have been developed. These systems have recently been used to clone novel and important genes, including disease resistance loci from Nicotiana tabacum, tomato and flax.

DNA Transposable Elements↗
PubMed1995

Minor Injuries Unit: expanding the scope of accident and emergency provision.

The Minor Injuries Unit at St Charles Hospital, London, opened in early 1993. Its establishment is placed in the context of radical changes occurring in Accident and Emergency provision within the UK. The unit's success has exceeded initial expectations and mirrors the potential for such units detailed in recent studies. The use of treatment and prescription protocols are discussed. The effective utilisation of existing and potential nursing skills is demonstrated.

Emergency Nursing↗
PubMed1995

A system for insertional mutagenesis and chromosomal rearrangement using the Ds transposon and Cre-lox.

A system for insertional mutagenesis and chromosomal rearrangement in Arabidopsis has been developed. The T-DNA vectors are based on the maize transposon Ds, lox sites from the Cre-lox site-specific recombination system, and transcriptional fusions expressing Ac transposase or Cre recombinase. The engineered transposon is termed Dslox. Transposed Dslox insertions were created by crossing plants bearing Dslox with plants expressing Ac transposase, then simultaneously selecting for excision and reinsertion in F2 seedlings using the herbicides chlorsulfuron and phosphonothricin, respectively. F2 plants bearing stable Dslox insertions were identified by scoring for the absence of the Ac transposase T-DNA, using a novel, visual marker in that T-DNA. Two independent Dslox insertions were characterized and placed 5.6 and 16.5 cM from their T-DNAlox, which mapped close to m506 on chromosome 4. Plants bearing either of the two different transposed Dsloxs and T-DNAlox were crossed to plants expressing Cre recombinase, which catalyzed recombination between the lox site in transposed Dslox and the lox site in T-DNAlox. Lox-lox recombinants were identified selectively amongst progeny of these crosses. Molecular and genetic analysis of the lox-lox rearrangements indicated that both were inversions. The smaller inversion was germinally transmitted from generation to generation as a simple trait, whereas the larger inversion was not transmitted to progeny of plants bearing the rearrangement.

Arabidopsis↗
PubMed1995

The successful utilization of nonlicensed assistive staff in a critical care area.

Health care organizations are under public and political pressure to control costs, produce quality outcomes, and have high client/patient satisfaction levels. To reduce costs and capitalize on the talents and skills of professional nurses, a variety of organizational redesigns, reengineerings, and new role creations are taking place. This article explores the use of nonlicensed assistive/supportive staff in a critical care unit. The focus includes the salient objectives for the use of assistive/supportive staff, as well as criteria for decisions and design and a developmental model for role development.

Allied Health Personnel↗
PubMed1995

Cloning and expression of melanin-concentrating hormone genes in the rainbow trout brain.

Salmonids, a group of tetraploid fish including salmon and trout, produce the vertebrate neuropeptide melanin-concentrating hormone (MCH) in a group of hypothalamic magnocellular neurons in the nucleus lateralis tuberis (NLT). NLT neurons project both to the brain and to the neural lobe of the pituitary gland from where MCH is released into the circulation to play a central role in camouflage (+/- stress). We have cloned and sequenced the MCH1 and MCH2 genes from the rainbow trout, Oncorhynchus mykiss, and used the data firstly to examine the position of O. mykiss in salmonid phylogeny, and secondly to enable central nervous system MCH1 and MCH2 gene expression to be mapped. In the immature adult female trout brain, only MCH2 was detectable at the hybridization stringency used. In addition to the known location of MCH-positive neurons, immunocytochemistry and in situ hybridization histochemistry revealed a previously undescribed nucleus of MCH-positive neurons located more dorsal and posterior to those of the NLT, over the paraventricular organ of the lateral ventricular recess. Axons from this second group of MCH neurons project dorsally into the brain, while a few extend down toward the lateral ventricle near the paraventricular organ. They make little, if any, direct contact with the neurohypophysis, and thus may subserve a central function, unrelated to hormonal colour regulation.

Amino Acid Sequence↗
PubMed1994

The product of the tobacco mosaic virus resistance gene N: similarity to toll and the interleukin-1 receptor.

The products of plant disease resistance genes are postulated to recognize invading pathogens and rapidly trigger host defense responses. Here we describe isolation of the resistance gene N of tobacco that mediates resistance to the viral pathogen tobacco mosaic virus (TMV). The N gene was isolated by transposon tagging using the maize Activator transposon. A genomic DNA fragment containing the N gene conferred TMV resistance to TMV susceptible tobacco. Sequence analysis of the N gene shows that it encodes a protein of 131.4 kDa with an amino-terminal domain similar to that of the cytoplasmic domain of the Drosophila Toll protein and the interleukin-1 receptor (IL-1R) in mammals, a nucleotide-binding site (NBS), and 14 [corrected] imperfect leucine-rich repeats (LRR). The sequence similarity of N, Toll, and IL-1R suggests that N mediates rapid gene induction and TMV resistance through a Toll-IL-1-like pathway.

Amino Acid Sequence↗
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↗