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Biomedical subjects

H J Dean

Publications and source records attributed to H J Dean.

At least 37 records · Page 2Linked to original sources

A 3' coterminal gene cluster in pseudorabies virus contains herpes simplex virus UL1, UL2, and UL3 gene homologs and a unique UL3.5 open reading frame.

We have determined the nucleotide sequence and transcription pattern of a group of open reading frames of pseudorabies virus (PRV), which are located at the right end of the BamHI-G fragment from 0.664 to 0.695 map units in the unique long region of the genome. Nucleotide sequence analysis revealed four open reading frames. The first three correspond in genome location to the herpes simplex virus type 1 (HSV-1) open reading frames UL1, which codes for glycoprotein L (gL); UL2, which codes for a uracil-DNA glycosylase; and UL3, which codes for a polypeptide of unknown function. The fourth open reading frame, UL3.5, is not present in the HSV-1 genome. Northern (RNA) blot analysis with oligonucleotide and cDNA probes revealed four abundant mRNA species of 3.3, 2.7, 1.8, and 0.9 kb, which are likely to yield polypeptides encoded by the UL1, -2, -3, and -3.5 open reading frames, respectively. All four transcripts were of the early-late kinetic class, transcribed in the same direction, and 3' coterminal. The UL2 and UL3 genes of PRV and HSV-1 have significant amino acid sequence homology, while the UL1 genes are positional homologs and the UL3.5 gene is unique to PRV.

Amino Acid Sequence↗

Non-insulin-dependent diabetes mellitus in Indian children in Manitoba.

OBJECTIVE: To report on our 7-year experience with non-insulin-dependent diabetes mellitus (NIDDM) in native Indian children in Manitoba and to raise the awareness of physicians about the difficulties in the classification and management of hyperglycemia in Indian children. DESIGN: Case series. PATIENTS: All Indian children under 15 years of age referred for evaluation and management of diabetes to the diabetes clinic at the Children's Hospital of Winnipeg between 1984 and 1990 who did not have a history of diabetic ketoacidosis. MAIN RESULTS: Sixteen girls and four boys aged 7 to 14 years at the time of diagnosis were identified as having NIDDM. All 16 children whose family history could be confirmed had at least one parent with NIDDM. Five of the 20 complained of polyuria or nocturia; the remainder presented with asymptomatic glycosuria. At the time of diagnosis the random serum glucose level varied from 15.0 to 30.8 mmol/L, the fasting serum insulin level from 45 to 300 pmol/L and the total glycated hemoglobin level from 7.1% to 23.3%. Twelve of the children had been followed for at least 4 years. Six of the 12 had received insulin therapy at some time, including during pregnancy. At the time of writing, none was receiving therapy with insulin or orally given hypoglycemic drugs. All were encouraged to follow a weight-reduction diet and exercise regimen. During follow-up the mean total glycated hemoglobin level for each patient varied from 9.1% to 20.9%; none maintained a glycated hemoglobin level in the normal range. CONCLUSIONS: NIDDM occurs in Indian children under 15 years of age. The clinical features at presentation occasionally mimic those of insulin-dependent diabetes. A strong family history of NIDDM and lack of diabetic ketoacidosis during follow-up support the diagnosis of NIDDM. Adherence to a diet and exercise regimen has been poor. The conventional diabetes education approach may not be appropriate for this population.

Adolescent↗

Predictive value of short-term growth using knemometry in a large population of healthy children.

We have analyzed the lower leg growth using a knemometer and the height growth using a stadiometer of 90 healthy children aged 3-16 years, for one year. The intra- and inter-individual monthly lower leg growth varied up to 4-fold, which was not accounted for by age or sex. The correlation between short term and annual lower leg growth rates increased with longer observation periods. There was no month-to-month consistency in the ratio of lower leg growth and height growth. There was no correlation between 1 month lower leg growth and annual height growth. The correlation increased with time. The 6-month observation interval was the interval with the highest predictive value for annual lower leg growth (R2 = 0.727) and annual height growth (R2 = 0.732). We conclude that growth of different parts of the skeleton and variable interval growth rates limits the ability of knemometry to predict long term growth.

Adolescent↗

The effect of leg position on knemometric measurements of lower leg length.

Using the Valk knemometer, lower leg length (LLL) was assessed relative to changes in the positioning of the upper leg. Lowering the chair height of the knemometer resulted in a more acute angle between the upper and lower leg and a decrease in LLL. This decrease in measurement was attributed to changes in the anatomical surface of the knee underlying the measuring platform as a result of increasing the acuity of the leg angle. Based on four different leg positions, the average change in LLL per centimeter change in chair height was 0.607 mm in a child sample of 50, and 0.655 mm in an adult sample of 20. The difference in chair height with the leg angle at 90 degrees and the lowest chair height possible, ranged from 12.3 to 30.3 mm, relative to lower leg length. This meant the longest leg in the study had a LLL measurement differing by 19.8 mm between these two positions. Due to the effect of leg position, we advised the use of a standard method of measuring LLL with respect to leg angle. Given the difficulties in accurately measuring leg angle with current available tools, we advise the most acute angle.

Adolescent↗

Isolation and characterization of lymphocytes from bovine intestinal epithelium and lamina propria.

The lymphocyte populations of the bovine gut lamina proprial (LP) and epithelial tissues were isolated and characterized with respect to cells bearing surface and cytoplasmic immunoglobulin (Ig). Functional characteristics of cells from the two tissues, including responsiveness to Concanavalin A (Con A), anti-bovine immunoglobulin (anti-Ig), Con A supernatants of bovine peripheral blood lymphocytes (bConA sup) and recombinant human IL-2 (rhIL-2), were also assessed. Less than 1% of the mononuclear cells in the epithelial tissue (IEL) stained for cytoplasmic Ig, and 9% stained positively for surface Ig. IEL did not proliferate in response to anti-Ig, although cells of this population did respond to Con A, bConA sup, and rhIL-2. Twenty-seven percent of bovine gut LP lymphocytes stained for surface Ig, while 39% of these cells were positive for cytoplasmic Ig. LP lymphocytes proliferated in response to all four stimulants used, Con A, anti-Ig, bConA sup and rhIL-2.

Animals↗

Insulin and insulin-receptor autoantibodies in children with newly diagnosed IDDM before insulin therapy.

Twenty-nine children, aged 1-15 yr, with newly diagnosed insulin-dependent diabetes mellitus (IDDM) had sera taken before insulin therapy to be examined for the presence of insulin-receptor antibodies by measuring the inhibition of binding of radiolabeled insulin to IM-9 lymphocytes in both whole serum and purified IgG fractions. Groups of children with long-standing IDDM and autoimmune endocrine disease as well as a normal control group were studied. A positive result, defined as binding greater than or equal to 2 SD below the mean zero standard, was found in 3 (10.3%) of the 29 newly diagnosed diabetic patients. As a group, they showed significantly greater binding inhibition than the normal control group for both whole serum and purified IgG (one-tailed t test, P less than .05 and P less than .002, respectively). Insulin autoantibodies were also measured by a sensitive radioimmunoassay technique. A positive result, defined as binding greater than 3 SD above the normal control pooled sera, was found in 9 (37.5%) of 24 of the newly diagnosed IDDM group tested. All 3 subjects positive for insulin-receptor antibodies were also positive for insulin autoantibodies, whereas 6 of the 21 receptor-antibody-negative subjects were positive for insulin autoantibodies (Fisher's exact test, P = .0415). This suggests the possibility that the presence of insulin autoantibodies is a prerequisite for the development of insulin-receptor antibodies, i.e., as an anti-idiotypic response. Insulin-receptor antibodies and insulin autoantibodies may play a currently undefined pathophysiologic role in the development of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Growth hormone therapy in Canada: end of one era and beginning of another.

This paper reviews the difficulties in diagnosing a true deficiency of growth hormone (GH), the long-term results of therapy, the Canadian experience in treating GH deficiency, including the contributions made by the Medical Research Council's Therapeutic Trial of Human Growth Hormone, and the occurrence of Creutzfeldt-Jakob disease in recipients of GH therapy. It also speculates on potential alternatives to treatment with GH derived from human pituitaries.

Adult↗

Growth hormone deficiency in patients with histiocytosis X.

Twenty-two patients with biopsy proved histiocytosis X, aged 10 months to 14 years (median 2 years) at the time of diagnosis, were observed for 6 months to 13 years (median 4 years). One patient who had received 3000 rads irradiation directly to the hypothalamic-pituitary area had clinical and biochemical evidence of growth hormone deficiency and responded to GH therapy. Thirteen patients had normal stature, normal growth velocity, and no diabetes insipidus. The GH response to insulin-induced hypoglycemia was studied in three of these 13 patients (group 1), in three children with short stature and no diabetes insipidus (group 2), and in five patients with diabetes insipidus but normal stature and growth velocity (group 3). Peak GH responses were normal (greater than 5 micrograms/L) in all patients in groups 1 and 2, but three of the five patients in group 3 had subnormal GH responses to insulin-induced hypoglycemia and to arginine, L-DOPA/propranolol, and exercise. Their growth rates continue to be normal over 6 to 14 years follow-up. Thus, although impaired GH responses were observed in four of the 12 patients tested, true growth failure occurred only in association with direct hypothalamic-pituitary irradiation. This experience and the observation that GH deficiency was diagnosed in fewer than 1% of children with histiocytosis in Canada during a 15-year period (accounting for less than 1% of all children with GH deficiency) suggest that classic GH deficiency is not a common complication of histiocytosis unless direct hypothalamic-pituitary irradiation has been given.

Child↗

Benign course after massive levothyroxine ingestion.

Management of thyroid hormone ingestion is controversial. We present nine children with massive levothyroxine ingestion who experienced a benign course. Their serum thyroxine levels ranged from 19.9 to 84.7 micrograms/dl. Seven were clinically euthyroid, and the other two had mild symptoms. No specific therapy was given. We recommend gastrointestinal decontamination procedures and serum thyroxine levels for an ingestion of greater than 2.0 mg of levothyroxine (or its equivalent). If levothyroxine has been ingested, neither immediate hospitalization nor prophylactic antihyperthyroidism therapy is recommended. If the initial serum thyroxine level is significantly elevated, close outpatient follow-up, especially during days three to 10, is warranted. However, massive ingestion of thyroid extract or triiodothyronine may require immediate hospitalization for observation. Therapeutic interventions aimed at extracorporeal removal of excess thyroid hormones are not recommended. Specific antithyroid therapy should be reserved for those rare patients with significant symptoms of thyrotoxicosis.

Adolescent↗

The educational, vocational, and marital status of growth hormone-deficient adults treated with growth hormone during childhood.

The goal of growth hormone therapy in childhood is to increase stature, thereby facilitating normal psychosocial development. To determine the social outcome of patients with growth hormone deficiency (GHD), we interviewed 116 adults with GHD across Canada, including 86 men and 30 women 18 to 38 years of age who were treated with growth hormone during childhood. The education of the 96 patients who had completed their formal education was similar to their siblings and to the general population. Of the patients in the labor force, 35.4% were unemployed; the unemployment rates for those patients less than 25 years of age and those 25 years of age or older were 45% and 23%, respectively, compared with national rates of 21.2% and 9.4% for the same age groups, respectively. Of the 90 patients with GHD who were not attending school, 70 lived with their parents or relatives. Only 15 patients were married; one was divorced. The percentage of patients with GHD who were married was less than 30% of the expected age-adjusted rate. No difference in the rate of employment or marriage was found between the patients with idiopathic isolated GHD and organic hypopituitarism. In summary, the achievements of patients with GHD seem to be normal in the education system, but the rate of employment and marriage are much lower than expected. This poor outcome was unrelated to the response to growth hormone therapy and emphasizes the need to develop strategies that lead to more satisfactory psychosocial integration of patients with GHD in adult life.

Adolescent↗

The effect of five synthetic progestational compounds on 5 alpha-reductase activity in genital skin fibroblast monolayers.

The suggestion has been made that prenatal exposure to synthetic progestogens contributes to an increased incidence of hypospadias. One potential mechanism for such an effect might be inhibition of 5 alpha-reductase, a key enzyme in normal male sexual differentiation. We have examined the effect of progesterone and of five synthetic progestogens upon 5 alpha-reductase activity in fibroblast monolayers from 12 genital skin cell lines obtained from normal newborn infants, boys with phimosis and hypospadias and a normal adult male. Basal enzyme activities ranged from 0.8-12.1 pmoles 5 alpha-reduced product/micrograms DNA/hour. Progesterone and norethindrone inhibited 5 alpha-reductase activity in a dose dependent manner to a maximum of 95% and 50% of basal levels respectively at 10(-5) M. Similar concentrations (10(-5) M) of norethynodrel, ethisterone, dl-norgestrel and d-norgestrel had little or no effect. Studies of cell viability showed that the effects of progesterone and norethindrone were specific for 5 alpha-reductase and not non-specific toxic effects.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗