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Biomedical subjects

G Werther

Publications and source records attributed to G Werther.

10 recordsLinked to original sources
PubMed2001

Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele.

Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease with both genetic and environmental components. In addition to the human leukocyte antigen (HLA) complex, the single major genetic contributor of susceptibility, an unknown number of other unidentified genes are required to mediate disease. Although many loci conferring susceptibility to T1D have been mapped, their identification has proven problematic due to the complex nature of this disease. Our strategy for finding T1D susceptibility genes has been to test for human homologues of loci implicated in diabetes-prone NOD (non-obese diabetic) mice, together with application of biologically relevant stratification methods. We report here a new susceptibility locus, IDDM18, located near the interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B alleles was observed in affected sibpairs and was confirmed in an independent cohort of simplex families. A single base change in the 3' UTR showed strong linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR alleles showed different levels of expression in cell lines. Variation in IL-12p40 production may influence T-cell responses crucial for either mediating or protecting against this and other autoimmune diseases.

3' Untranslated Regions↗
PubMed1996

Psychosocial and family functioning in children with insulin-dependent diabetes at diagnosis and one year later.

Examined the initial impact and subsequent adjustment to the diagnosis of insulin-dependent diabetes mellitus (IDDM). Children between 1 and 14 years of age and their families were assessed several weeks after diagnosis and again a year later using standardized measures of child behavior, parental mental health, and family functioning. Immediately after diagnosis, the children and both parents exhibited mild symptoms of psychological distress but these had largely resolved at 12-month follow-up. The impact of IDDM diagnosis on family functioning varied with informant, SES, and the age of the child, with an overall tendency for families to become less flexible over the year. Findings suggest that most children and their parents exhibit satisfactory individual adjustment after a period of initial stress but family functioning is affected in complex ways. Serial follow-up of the cohort is planned to establish whether the current findings are predictive of longer term outcome.

Adaptation, Psychological↗
PubMed1991

Abnormal regulation of insulin-like growth factor binding proteins in adolescents with insulin-dependent diabetes.

We have measured fasting 0800 h insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-3, in 52 diabetic adolescents and 74 puberty-matched control subjects with short stature and normal hormonal status. We have also measured overnight hourly profiles of IGFBP-1, glucose, free insulin, and GH in 12 of the diabetic adolescents. With advancing age and pubertal status, IGFBP-1 declined and IGFBP-3 increased significantly in the control, but not the diabetic group. Fasting IGFBP-1 levels were elevated 4-fold compared to controls. Median IGFBP-3 was significantly lower in the diabetic compared to the control group in pubertal stages III and V. Elevated IGFBP-1 was significantly correlated with metabolic control in poorly controlled subjects (mean 12-month glycosylated haemoglobin greater than 8.5%). In the overnight profiles, mean hourly IGFBP-1 was inversely related to insulin, but not glucose. As free insulin levels declined, IGFBP-1 rose, associated with rising predawn blood sugars. The integrated 3-h IGFBP-1 value (0500-0800 h) was significantly correlated with the corresponding glucose integrated value. IGFBP-1 area under the curve for the whole overnight profile was significantly correlated with glycosylated hemoglobin in 11 of the 12 subjects. IGFBP-1 from diabetic adolescents has been shown to inhibit IGF-I bioactivity. We postulate that IGFBP-1 may have a role in growth impairment of poorly controlled diabetes and may contribute to the dawn phenomenon.

Adolescent↗
PubMed1987

Precocious puberty associated with malignant thoracic teratoma and malignant histiocytosis in a child with Klinefelter's syndrome.

A 10-year-old boy with precocious puberty of 2 1/2 years' duration presented with a malignant thoracic teratoma with elevated levels of beta human chorionic gonadotropin (beta-HCG) and alpha fetoprotein (alpha FP). The mediastinal tumor was completely excised and adjuvant chemotherapy commenced. Within 3 weeks of commencing chemotherapy he developed hematologic abnormalities that, with the subsequent clinical illness, led to a diagnosis of malignant histiocytosis. Death occurred a few days after start of therapy for malignant histiocytosis. Cytogenic studies showed the somatic karyotype to be that of Klinefelter's syndrome, while the malignant cells in marrow and lymph node carried an additional marker chromosome. This case, with others reported, suggest that the XXY karyotype may influence the development of mediastinal germ cell tumors, which in themselves appear to be associated with the early onset of a malignancy of the hemopoietic system.

Child↗
PubMed1980

24-hour metabolic profiles in diabetic children.

15 metabolic profiles were performed on 10 diabetic children who were on once-daily injections of insulin. Blood and urine glucose concentrations were high throughout much of the day and night, and were associated with abnormal levels of blood ketones, lactate, and pyruvate. The plasma free-insulin profiles gave a characteristic pattern for each type of insulin. The investigation gives valuable information for the clinical management of such children.

Adolescent↗
PubMed1979

Relationship between urinary and blood glucose in diabetic children.

The relationship of urine glucose concentration with 'average' blood glucose concentration for the corresponding period was investigated in 10 juvenile diabetics during the performance of 15 inpatient metabolic profiles. 0% glucosuria was associated with 'average' blood glucose concentrations less than 6.4 mmol/l (less than 115 mg/100ml), 2% glycosuria with concentrations greater than 8.6 mmol/l (greater than 154 mg/100ml), and over 5% glycosuria with concentrations greater than 11.3 mmol/l (greater than 204 mg/100ml). Urinary glucose loss was large (greater than 278 mmol; greater than 5g) when the 'average' blood glucose was greater than 11.1 mmol/l (greater than 200 mg/100ml). Because many diabetics have blood glucose concentrations up to 11.1 mmol/l, it is advantageous if glucosuria up to 5% is detectable by routine home urine tests. The 2-drop Clinitest method detects glycosuria up to 5% without significant loss of accuracy and is recommended in preference to the 5-drop method.

Adolescent↗