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Biomedical subjects

J Baker

Publications and source records attributed to J Baker.

At least 19 recordsLinked to original sources

Has the process causing noninsulin dependent diabetes start at birth? Evidence in neonates from a population with a high prevalence of diabetes.

AIMS: to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes. METHODS: fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers. RESULTS: the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies. CONCLUSIONS: the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation.

Adult

Sequence and characterization of the gcpE gene of Escherichia coli.

In Escherichia coli, the gene gcpE encodes a protein of unknown function and lies immediately upstream of the hisS gene for histidyl-tRNA synthetase. The nucleic acid sequence of gcpE predicts an open reading frame for a protein of 40,681 Da. The probable transcription terminator of gcpE overlaps the hisS promoter. Haploid cells containing a disrupted gcpE could not be obtained, suggesting that the gcpE gene is essential.

Amino Acid Sequence

The relationship between body mass index and socioeconomic status in New Zealand: ethnic and occupational factors.

AIMS: the relationship between body mass index (BMI) and socioeconomic status (SES) was examined in a multiracial New Zealand workforce in order to investigate ethnic variations. METHODS: an employed population of 5673 people were measured for weight and height and BMI calculated. Socioeconomic status was assigned using the UK Registrar General's scale. RESULTS: both European women and men showed an inverse relationship of increasing BMI with decreasing SES which is typical of developed societies. Maori, Pacific Islanders and Asians did not, but neither did they show the direct relationship of developing societies. Examination of the components of SES showed that combined family income did not influence BMI in any ethnic group but that education was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Maori (p = 0.0603), and occupation was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Pacific Islanders (p = 0.0148) independently of education. CONCLUSIONS: ethnic variations are partly explained by educational levels and occupation, but not by income. Increased education may decrease prevalence of obesity. Some occupational factors are discussed.

Adult

Toremifene and its metabolites enhance doxorubicin accumulation in estrogen receptor negative multidrug resistant human breast cancer cells.

The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50 = less than 0.1 microgram/ml MDA 231; IC 50 = 100 micrograms/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18-20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0-G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N-desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show evidence that toremifene and its active metabolites are present in high concentrations in human plasma following a single 200 mg oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents

Measuring the albumin excretion rate: agreement between methods and biological variability.

A timed urine collection is necessary to determine the excretion rate of albumin (AER) but such specimens are tedious to collect and frequently inaccurate. Albumin excretion can also be quantified by the use of the albumin:creatinine ratio in randomly obtained specimens. In the present study the agreement between AER as measured on a 24-h urine collection and as estimated from the albumin:creatinine ratio is determined. Previously published studies have examined the correlation rather than the agreement between these methods and not taken into account the biological variability of AER. Thirty patients with diabetes who had normal renal function, but varying degrees of albuminuria, produced two 24-h specimens and two random daytime specimens of urine. AER was measured on the former and estimated from the latter by multiplying the albumin:creatinine ratio by an estimate of that individual's creatinine excretion rate. Agreement between the methods and the biological variability was determined by using appropriate statistical methodology, the main outcome measure being the limits of agreement between repeat values for both measurements and both estimates of AER, and between the averages of the measurements and the estimates. The limits of agreement between repeated 24-h measurements were wide, the second specimen being 33 to 490% of the first. The estimates of AER gave values numerically similar to the measurements. The limits of agreement between the two estimates did not differ significantly from those of the measurements, nor did the limits of agreement when the average of the measurements and the average of the estimates were compared (all NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria

Albuminuria in people at least 40 years old: effect of obesity, hypertension, and hyperlipidemia.

Concentrations of urinary albumin and the albumin:creatinine ratio were measured in early-morning urine specimens from 5670 people older than 40 years who participated in a health screening survey of a local workforce. Sex-specific reference intervals were determined in a subgroup of 3597 people after excluding 2073 individuals with Albustix-positive proteinuria; diabetes mellitus; bacteriuria; current hypertension; body mass index greater than or equal to 30 kg/m2; or serum triglyceride greater than or equal to 2.5 mmol/L. The 97.5 percentile concentration for urinary albumin was 28 mg/L in men and 29 mg/L in women; for the albumin:creatinine ratio this was 2.3 g/mol in men and 2.8 g/mol in women. In the study population, the degree of albuminuria showed piecewise log-linear relationships with diastolic blood pressure (P = 0.0001) and body mass index (P = 0.0001), log-linear relationships with hypertriglyceridemia (P = 0.0001) and hypercholesterolemia (P = 0.0001), and a negative piecewise linear relationship with high-density lipoprotein (HDL) cholesterol (P = 0.0461).

Adult

Prevalence of diabetes mellitus and impaired glucose tolerance in a New Zealand multiracial workforce.

A cross sectional survey was carried out among a multiracial workforce of 5677 staff aged 40 to 64 years at worksites in Auckland and Tokoroa to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). The prevalences of diabetes mellitus and IGT were both similar for men and women, but increased with age. The relative risks for diabetes mellitus and for IGT were both inversely associated with gross annual household income, independent of age and ethnicity, being 1.61 (95% Cl = 1.10, 2.37) and 1.80 (95% Cl = 1.21, 2.67) respectively, in the lowest income group (less than $30,000) compared with the highest (greater than $40,000). Compared with Europeans, the relative risk of diabetes mellitus was significantly increased among Maori (3.63; 95% Cl = 2.48, 5.32), Pacific Islanders (2.34; 95% Cl = 1.50, 3.66) and Asians (5.97; 95% Cl = 2.61, 13.65), after controlling for age, income and body mass index. The increased prevalence of diabetes mellitus among Maori and Pacific Islanders, but not in Asians, could be partly attributed to their increased levels of obesity compared with Europeans. However, other factors, in addition to obesity, explain the increased diabetes prevalence in nonEuropean groups.

Adult

Clinical trials of a dual-sensor diagnostic pacemaker.

The results of clinical trials of a dual-sensor diagnostic pacemaker are described. The system monitors and records intraventricular electrical and pressure waveforms using a special lead incorporating bipolar electrodes together with a piezoelectric pressure transducer. The recorded waveforms, which are shown in conjunction with Holter recordings made simultaneously, demonstrate the value of pressure measurements and illustrate several cardiac events, including an ECG pause, bradycardia, a pressure pause, ectopic beats and tachycardia. The pacing function of the device is shown and capture is demonstrated.

Arrhythmias, Cardiac

Integrin alpha 6/beta 4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion.

The alpha 6/beta 4 complex is a member of the integrin family of adhesion receptors. It is found on a variety of epithelial cell types, but is most strongly expressed on stratified squamous epithelia. Fluorescent antibody staining of human epidermis suggests that the beta 4 subunit is strongly localized to the basal region showing a similar distribution to that of the 230-kD bullous pemphigoid antigen. The alpha 6 subunit is also strongly localized to the basal region but in addition is present over the entire surfaces of basal cells and some cells in the immediate suprabasal region. By contrast staining for beta 1, alpha 2, and alpha 3 subunits was very weak basally, but strong on all other surfaces of basal epidermal cells. These results suggest that different integrin complexes play differing roles in cell-cell and cell-matrix adhesion in the epidermis. Immunoelectron microscopy showed that the alpha 6/beta 4 complex at the basal epidermal surface is strongly localized to hemidesmosomes. This result provides the first well-characterized monoclonal antibody markers for hemidesmosomes and suggests that the alpha 6/beta 4 complex plays a major role in epidermal cell-basement membrane adhesion. We suggest that the cytoplasmic domains of these transmembrane glycoproteins may contribute to the structure of hemidesmosomal plaques. Immunoultrastructural localization of the BP antigen suggests that it may be involved in bridging between hemidesmosomal plaques and keratin intermediate filaments of the cytoskeleton.

Animals

Temporal regulation of gene expression in the blastoderm Drosophila embryo.

The Drosophila embryo undergoes a developmental transition during cycle 14 when it initiates asynchronous mitotic cycles and markedly increases its rate of zygotic transcription. The nucleo-cytoplasmic ratio has been proposed to be the single factor that temporally regulates this developmental transition. We altered the ratio in the embryo and analyzed the consequences on the cell cycle program and on the transcripts of specific genes. These genes were chosen because their transcripts normally undergo changes in pattern during cycle 14. We found evidence that the nucleo-cytoplasmic ratio is read and interpreted locally to regulate the cell cycle program. Based on the response of the transcripts to changes in the ratio, we found evidence that at least two classes of temporal regulatory mechanisms control these transcripts. We therefore propose two corresponding classes of transcripts: (1) nucleo-cytoplasmic ratio dependent; and (2) nucleo-cytoplasmic ratio independent or time correlated. The temporal regulation of the ratio-independent transcripts may be dependent on developmental time. We conclude that multiple modes of temporal regulation underlie the events of the developmental transition in Drosophila embryogenesis.

Animals

Cohort reconstruction: which infants can be restudied at school age?

Longer-term follow-up of infants with specific health concerns, such as low birthweight, is critical to assessing the effect of medical interventions. This report examines the approach of reconstructing previously studied cohorts in terms of the factors discriminating between respondents and non-respondents. Follow-up was attempted during 1987-1988 for 1875 children born during a 6-month period in 1978 in three geographically defined regions in the United States, for whom 1-year assessments of health and developmental status were obtained at 1 year of age as part of a previous study. For a 25% sample, participation involved a clinic visit for developmental assessments; for the remainder an interview by telephone or home visit. Follow-up was obtained for 72.5% of the cohort. Refusal rates were low (7%); most non-response was due to an inability to locate the families. Predictors of non-response reflected primarily low socio-economic status; completion rates were not influenced by mode of assessment. The role of a tracing agency is discussed. We conclude that cohort reconstruction is feasible with response rates comparable to some prospective studies with ongoing cohort maintenance.

Child Development

Independent roles of centrosomes and DNA in organizing the Drosophila cytoskeleton.

The early embryonic divisions of Drosophila melanogaster are characterized by rapid, synchronized changes of the nuclei and surrounding cytoskeleton. We report evidence that these changes are carried out by two separately organized systems. DNA was sufficient to cause assembly of nuclear lamina and the formation of nuclear membrane with pore structures. Free centrosomes were correlated with the formation of microtubule, microfilament and spectrin networks in the absence of nuclei. In addition, we found that the morphology of the cytoskeleton associated with the free centrosomes cycled in response to the embryonic cell cycle cues. These observations suggest that the centrosomes may be responsible for the organization of this extensive cytoskeleton. The early divisions may therefore result from the independent cycling of two systems, the nucleus and the surrounding cytoskeleton, that respond separately to the mitotic cues in the embryo and function together to give the synchronized early divisions. The Drosophila embryo has an "intermediate" mitotic system in which the nuclear membrane does not break down completely during mitosis. We speculate that the principles of cytoskeleton organization in this system may be different from those of the Xenopus "open" mitotic system.

Actin Cytoskeleton