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Biomedical subjects

J Baker

Publications and source records attributed to J Baker.

At least 163 records · Page 9Linked to original sources
PubMed1994

Liver regeneration: a comparison of in situ hybridization for histone mRNA with bromodeoxyuridine labeling for the detection of S-phase cells.

We developed an in situ hybridization technique for measurement of proliferative cell numbers through detection of histone mRNA in routinely fixed, paraffin-embedded tissue sections. Histone gene expression is coordinated with the cell cycle, and the increase in expression during S-phase permits unambiguous identification of cells undergoing DNA replication. Histone mRNAs were identified in routinely processed rat liver tissue by non-isotopic in situ hybridization with digoxigenin-labeled oligonucleotide probes. Specific hybrids were detected with alkaline phosphatase-labeled anti-digoxigenin antibody and visualized by BCIP-nitroblue tetrazolium indicator substrate. Unequivocal cytoplasmic labeling was observed in various cell types in the liver remnant during the first 72 hr after a two-thirds partial hepatectomy. The spatial and temporal patterns of histone labeling were almost identical to those obtained by staining with an antibody to bromodeoxyuridine. The identification of histone mRNA appears to be a reliable marker of the S-phase fraction, a technique with the further advantage that the tissue does not have to be first exposed to a nucleotide analogue. Hence, retrospective studies are possible. The probes can be applied to human and animal cells and tissues because the nucleotide sequences of histone genes are conserved.

Animals↗
PubMed1994

Cardiac allotransplantation across the ABO-blood group barrier by the neutralization of preformed antibodies: the baboon as a model for the human.

The baboon, like the human, expresses A and/or B blood group antigens on its tissues. Anti-A and anti-B antibodies are directed against these antigens, the epitopes of which are carbohydrate structures. Portions of these carbohydrates have been synthesized (trisaccharides A and B, respectively). When infused intravenously, the synthetic trisaccharides form a complex with the specific antibodies and neutralize their activity preventing them from binding to the antigen targets on a transplanted organ. In nonimmunosuppressed, hyperimmunized baboons, the continuous intravenous infusion of the specific trisaccharide alone (for 6 days) inhibited rejection of ABO-incompatible cardiac allografts, extending survival from a mean of 19 min (n = 3) to 8 days (n = 2), at which time the grafts failed from cellular (not vascular) rejection. The combination of long-term pharmacologic immunosuppression plus trisaccharide infusion (for periods of 8 to 19 days) extended survival to a mean of > 28 days (n = 4) with one heart functioning > 52 days. Accommodation clearly occurred in three of the four cases. This form of therapy may permit cadaveric organ allotransplantation across the ABO blood-group barrier in the human.

ABO Blood-Group System↗
PubMed1993

Budesonide inhibits plasma extravasation induced by capsaicin and by substance P in the rat nasal mucosa.

We studied the effect of the locally administered glucocorticoid budesonide on plasma extravasation induced by capsaicin and by substance P (SP) in the nasal mucosa of pathogen-free rats. Using Evans blue dye as a tracer, we measured plasma extravasation induced by capsaicin (150 micrograms kg-1 i.v.) or SP (0.5 and 2.5 micrograms kg-1 i.v.) in the rat naso- and maxilloturbinates after pretreatment with budesonide (0.1-50 micrograms twice/day for 2 days in the right nostril; 50 micrograms only for SP) or its vehicle. We found that budesonide inhibits plasma extravasation induced by capsaicin in a dose-dependent fashion in the nasal cavity. After the highest dose (50 micrograms) of budesonide, the values of Evans blue in the nasal mucosa were not different from the values observed after capsaicin vehicle alone. Budesonide also reduced plasma extravasation induced by capsaicin in the trachea and the urinary bladder of the rats in a dose-dependent fashion. Budesonide (50 micrograms) delivered to the nose inhibited the plasma extravasation caused by 0.5 but not by 2.5 micrograms SP kg-1 in the nasal mucosa. We conclude that the postjunctional part of the neurogenic pathway is a target for glucocorticoid antiinflammatory action in the nasal mucosa, at least of the rat. Budesonide's effect on organs other than the nose can be explained by systemic absorption.

Administration, Topical↗
PubMed1993

Characterization of [3H]meta-chlorophenylbiguanide binding to 5-HT3 receptors in N1E-115 neuroblastoma cells.

The binding characteristics of a radiolabelled 5-HT3 receptor agonist, [3H]meta-chlorophenylbiguanide (mCPBG), were examined in membranes from N1E-115 neuroblastoma cells. Scatchard plots of saturation binding data showed the presence of two populations of binding sites, with Kd = 0.03 +/- 0.01 nM and 4.4 +/- 1.2 nM and Bmax = 11.9 +/- 4.2 and 897.9 +/- 184.7 fmol/mg protein respectively. Competition studies with a selection of agonists and antagonists revealed the pharmacological profile expected for a 5-HT3 receptor. The rank order of potency for antagonists was granisetron > quipazine > GR65630 > ondansetron > MDL72222, and for agonists was mCPBG > 5-HT (5-hydroxytryptamine, serotonin) > 2-methyl-5-HT. IC50 values for 5-HT and 2-methyl-5-HT were lower than those observed using radiolabelled antagonists, and combined with functional experiments, the data suggest that [3H]mCPBG may label high affinity desensitized states of the receptor. We conclude that [3H]mCPBG labels 5-HT3 receptors in N1E-115 neuroblastoma cell membranes and may be a useful compound with which to explore 5-HT3 receptors in other systems.

Animals↗
PubMed1993

Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).

Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf-2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.

Amino Acid Sequence↗
PubMed1993

Role of insulin-like growth factors in embryonic and postnatal growth.

A developmental analysis of growth kinetics in mouse embryos carrying null mutations of the genes encoding insulin-like growth factor I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF1R), alone or in combination, defined the onset of mutational effects leading to growth deficiency and indicated that between embryonic days 11.0 and 12.5, IGF1R serves only the in vivo mitogenic signaling of IGF-II. From E13.5 onward, IGF1R interacts with both IGF-I and IGF-II, while IGF-II recognizes an additional unknown receptor (XR). In contrast with the embryo proper, placental growth is served exclusively by an IGF-II-XR interaction. Additional genetic data suggested that the type 2IGF/mannose 6-phosphate receptor is an unlikely candidate for XR. Postnatal growth curves indicated that surviving Igf-1(-/-) mutants, which are infertile and exhibit delayed bone development, continue to grow with a retarded rate after birth in comparison with wild-type littermates and become 30% of normal weight as adults.

Aging↗
PubMed1993

Hypertension and its treatment in a New Zealand multicultural workforce.

AIMS: To investigate ethnic variations in blood pressure levels and the likelihood of hypertension being treated in a multicultural New Zealand workforce. METHODS: An employed population of 5651 staff aged 40 to 64 years at worksites in Auckland and Tokoroa, who recorded their current prescribed medication, were measured for blood pressure, weight and height. Body mass index (BMI) was calculated. RESULTS: Mean blood pressure levels were higher in men than women, and increased with age and BMI. Compared with Europeans, mean systolic and diastolic blood pressures were higher in Maori (by 5 to 6 mmHg), Pacific Islanders (by 4 to 6 mmHg) and Asians (by 1 to 5 mmHg) after controlling for age and blood pressure treatment. This increase in Maori and Pacific Islanders, compared with Europeans, was approximately halved after also controlling for BMI, but still remained statistically significant (p < 0.05). In contrast, ethnic differences in BMI did not explain any of the blood pressure increase in Asians. In analyses restricted to hypertensive participants, the likelihood of hypertension being treated was higher in women than men (odds ratio (OR) = 3.42; 95% CI 2.13, 5.47), and lower in Maori (OR 0.33; 95% CI 0.19, 0.58), Pacific Islanders (OR 0.27; 95% CI 0.16, 0.47) and Asians (OR 0.29; 95% CI 0.10, 0.86) than Europeans. CONCLUSION: These results suggest that the likelihood of hypertension being treated is related to sex and ethnic group; and that other unknown factors, in addition to increased BMI levels, explain the higher blood pressure levels in Polynesians compared to Europeans.

Adult↗
PubMed1993

Serum lipid levels in a New Zealand multicultural workforce.

AIMS: To examine ethnic variations in serum lipid levels and to determine whether lipids are related to lifestyle variables in a New Zealand multicultural workforce. METHODS: Fasting blood samples were collected from 5671 employed people for determination of serum total and HDL cholesterol, triglycerides, and LDL cholesterol. Individual exposures over the previous three months to smoking, alcohol, leisure time physical activity were recorded, and weight and height were measured to calculate body mass index (BMI). RESULTS: Maori and Pacific Islanders had lower age-adjusted total and LDL cholesterol levels than Europeans, and these differences were increased by controlling for BMI. In contrast, age-adjusted mean (SE) HDL cholesterol levels were also lower in Maori (men = 1.17 (0.02); women = 1.38 (0.03) mmol/L) and Pacific Islanders (men = 1.17 (0.01); women = 1.30 (0.02) mmol/L) compared with Europeans (men = 1.20 (0.01); women = 1.47 (0.01) mmol/L), but when BMI, smoking and other variables were controlled, levels were significantly higher in Maori and Pacific Islanders. With serum triglycerides, the pattern was not consistent in Maori and Pacific Islanders. Age-adjusted mean levels in Maori (men = 2.25 (0.07) mmol/L; women = 1.53(0.07) mmol/L) were significantly higher (p < 0.05) than in Pacific Islanders (men = 1.82 (0.06); women = 1.34(0.05) mmol/L) of the same sex. After controlling for BMI and other variables, triglyceride levels were also significantly lower in Pacific Islanders than in Europeans and Asians. BMI and smoking were positively associated with total and LDL cholesterol and triglycerides, and negatively with HDL cholesterol, after controlling for alcohol and physical activity. CONCLUSION: Lifestyle risk factors, particularly BMI and smoking, are strongly related to serum levels of all major lipids. Ethnic variations in coronary heart disease mortality rates in New Zealand are more consistent with ethnic variations in triglycerides than with variations in the other serum lipids.

Adult↗
PubMed1993

Role of neurogenic inflammation in antigen-induced vascular extravasation in guinea pig trachea.

Conflicting results have been reported about the role of sensory nerves in the allergen-induced plasma extravasation in sensitized guinea pigs using capsaicin desensitization. To investigate the role of tachykinins released from sensory nerves in the anaphylactic reaction in guinea pigs in vivo, we used a selective inhibitor of neutral endopeptidase, phosphoramidon, and a selective neurokinin (NK)-1 receptor antagonist, CP-96,345. Male Hartley guinea pigs were sensitized to OVA by two i.p. injections (70 mg) at 1-wk intervals. Two wk later, the animals were anesthetized and OVA was administered for 2 min by aerosol through a tracheal cannula. Plasma extravasation was assessed by the photometric measurement of the extravasated Evans blue after formamide extraction. Administration of aerosolized OVA to sensitized guinea pigs increased dye extravasation in the trachea in a dose-dependent manner, an effect that was demonstrable 5 min after exposure to allergen and that reached a maximum 10 min after exposure. At 5 min after OVA (5%), phosphoramidon (2.5 mg/kg, i.v.) did not increase the amount of dye in the trachea significantly and CP-96,345 (4 mg/kg) did not decrease the extravasated dye. At 10 min after OVA, allergen-induced plasma extravasation was potentiated by phosphoramidon by 56%, and was inhibited by CP-96,345 (4 mg/kg) by 42%. In the presence of phosphoramidon, CP-96,345 reduced the OVA-evoked plasma extravasation at 10 min in a dose-related manner (0.1-4 mg/kg). CP-96,345 (4 mg/kg) did not affect plasma extravasation induced by platelet-activating factor (100 nmol/kg, i.v.). These results suggest that tachykinin release from sensory nerves after allergen challenge to airways in sensitized guinea pigs is not responsible for the early increase in plasma extravasation, but, tachykinin release appears to play an important role in the subsequent extravasation.

Animals↗
PubMed1993

The association of peripheral nerve compression and reflex sympathetic dystrophy.

35 patients who presented with reflex sympathetic dystrophy (RSD) are reported. Peripheral nerve compression was present in 86% of the patients (30). 50% of the patients (15) had a single nerve compression, and 50% had multiple nerve compressions. The high incidence of these entrapments should alert the clinician to check for this treatable problem early in the course of RSD.

Adult↗
PubMed1993

Dynamic changes in microtubule configuration correlate with nuclear migration in the preblastoderm Drosophila embryo.

Drosophila embryogenesis is initiated by a series of syncytial mitotic divisions. The first nine of these divisions are internal, and are accompanied by two temporally distinct nuclear movements that lead to the formation of a syncytial blastoderm with a uniform monolayer of cortical nuclei. The first of these movements, which we term axial expansion, occurs during division cycles 4-6 and distributes nuclei in a hollow ellipsoid underlying the cortex. This is followed by cortical migration, during cycles 7-10, which places the nuclei in a uniform monolayer at the cortex. Here we report that these two movements differ in their geometry, velocity, cell-cycle dependence, and protein synthesis requirement. We therefore conclude that axial expansion and cortical migration are mechanistically distinct, amplifying a similar conclusion based on pharmacological data (Zalokar and Erk, 1976). We have examined microtubule organization during cortical migration and find that a network of interdigitating microtubules connects the migrating nuclei. These anti-parallel microtubule arrays are observed between migrating nuclei and yolk nuclei located deeper in the embryo. These arrays are present during nuclear movement but break down when the nuclei are not moving. We propose that cortical migration is driven by microtubule-dependent forces that repel adjacent nuclei, leading to an expansion of the nuclear ellipsoid established by axial expansion.

Animals↗
PubMed1993

A patient education program.

Everyday language used by health care professionals in gastroenterology is often unfamiliar to patients, regardless of their level of education. Consequently, the best efforts to explain diagnoses to patients can result in confusion and anxiety instead of understanding. A patient education program was designed in an attempt to correct this problem. This article describes how the patient education program was developed and implemented.

Documentation↗
PubMed1993

Diabetes mellitus and employment: survey of a New Zealand workforce.

A cross-sectional survey of a 5670 multiracial New Zealand workforce aged > 40 years was used to determine the health status of people with diabetes mellitus in employment. One hundred and two workers (73 men, 29 women) had known diabetes mellitus (prevalence of 1.8%) of whom 91 individuals (89.2%) had Type 2 diabetes. Mean age of diabetic workers was 51.1 +/- 5.6 (SD) years and median duration of disease was 5.0 (range 0-51) years. Most subjects were asymptomatic, although only 31.4% of diabetic workers had fasting glucose concentrations and 35.5% had fructosamine concentrations within the mean +/- 2SD range of a matched control group. Moreover, 22.5% of diabetic participants had fasting hypertriglyceridaemia and 21.6% had microalbuminuria. Ethnicity (non-European vs European) and lack of insulin therapy were the most important predictors of poor glycaemic control. We advocate more aggressive therapy with insulin and with culturally sensitive education programmes to avert long-term macrovascular complications.

Adult↗
PubMed1993

Diabetes mellitus and employment: is there discrimination in the workplace?

The employment record of 102 diabetic workers (73 men, 29 women), identified in a cross-sectional survey of 5670 middle-aged people in a New Zealand workforce, was studied for evidence of discrimination in the workplace. Compared with 403 matched controls (292 men, 111 women), diabetic workers showed no significant differences in socioeconomic status, educational attainment, or distribution between occupational groups. Similarly, mean duration of current employment (12.3 vs 12.4 years), mean number of jobs in the past 5 years (1.25 vs 1.34 jobs), frequency of sickness absence, and mean number of hours worked each week (43.5 vs 43.3h) did not differ significantly between diabetic and non-diabetic groups. We found no significant differences in work stress, even among those diabetic individuals with poor blood glucose control. There was no convincing evidence across a broad spectrum of industry that diabetic workers did suffer discrimination in the workplace.

Absenteeism↗
PubMed1993

Ruthenium red, but not capsazepine reduces plasma extravasation by cigarette smoke in rat airways.

1. Cigarette smoke increases vascular permeability in rat airways by activating release of tachykinin from capsaicin-sensitive sensory nerves. However, the mechanism by which cigarette smoke induces secretion of sensory neuropeptides is unknown. Here we hypothesized that cigarette smoke activates sensory nerve endings via a mechanism similar to that of capsaicin. 2. We studied the effects of ruthenium red, an inorganic dye which blocks the cation influx promoted by capsaicin and of the capsaicin antagonist capsazepine on the increase in vascular permeability produced by cigarette smoke, capsaicin, hypertonic saline and substance P in the trachea of pentobarbitone anaesthetized rats. We also investigated the ability of cigarette smoke to desensitize sensory nerve fibres. 3. Ruthenium red (10 mM) by aerosol blocked the increase in vascular permeability induced by capsaicin (0.5 microM) and reduced the response to cigarette smoke (5 puffs) but did not affect responses evoked by hypertonic saline (7.2%) or by substance P (10 microM) (all given by aerosol). Aerosols of capsazepine (0.1 mM) prevented extravasation by capsaicin, but did not inhibit response to cigarette smoke, hypertonic saline or substance P. Finally, pre-exposure to a high dose of cigarette smoke (10 puffs) prevented the extravasation caused by cigarette smoke (5 puffs) itself and by intravenous capsaicin (150 micrograms kg-1), but not that by intravenous substance P (10 nmol kg-1). 4. The present results show that cigarette smoke: (a) increases vascular permeability in the rat airways by a mechanism that is not antagonized by capsazepine, and is partially sensitive to rutheniun red; (b)produces desensitization of capsaicin-sensitive sensory nerves. We propose that chemical(s) contained in or agent(s) produced by cigarette smoke in the airways share partially a common pathway with capsaicin to activate peptide release from capsaicin-sensitive sensory nerves, but do not bind to the putative 'capsaicin receptor'.

Aerosols↗
PubMed1993

Neutralizing monoclonal antibodies that distinguish three antigenic sites on human cytomegalovirus glycoprotein H have conformationally distinct binding sites.

Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map of two nonoverlapping antigenic sites that are bridged by a third antigenic site. Neutralization assays with 15 laboratory or clinical human cytomegalovirus strains indicated that the monoclonal antibodies recognize three antigenically variable and three conserved epitopes within the three antigenic sites. The variable-domain genes encoding monoclonal antibodies representing each of the three antigenic sites were cloned and sequenced, and molecular models of their binding sites were generated. Conformational differences in the antibody-binding sites suggested a structural basis for experimentally observed differences in gH epitope recognition.

Amino Acid Sequence↗