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Biomedical subjects

D Hinton

Publications and source records attributed to D Hinton.

At least 19 recordsLinked to original sources

The period gene encodes a predominantly nuclear protein in adult Drosophila.

The period gene of Drosophila melanogaster (per) is important for the generation and maintenance of biological rhythms. Previous light microscopic observations indicated that per is expressed in a variety of tissues and cell types and suggested that the per protein (PER) may be present in different subcellular compartments. To understand how PER influences circadian rhythms, it is important to define its subcellular location, especially in adult flies where inducible promoter experiments suggested that it is most relevant to circadian locomotor activity rhythms. To this end, we report the results of an immunoelectron microscopic analysis of wild-type flies and per-beta-galactosidase (beta-gal) fusion gene transgenics using a polyclonal anti-PER antibody or an anti-beta-gal antibody, respectively. Most of the PER antigen and the fusion gene product were located within nuclei, suggesting that PER acts in that subcellular compartment to affect circadian rhythms. The results are discussed in terms of per's possible biochemical functions.

Animals

Nutritional status of home hemodialysis patients.

We studied the nutritional status of 32 patients (23 men), aged 50 (SD14) yr, on home hemodialysis (HHD) for one-138 months. No formal dietary restrictions were imposed. Anthropometric measurements were made using standard techniques, diet assessed by three-day dietetic diary and interview and plasma concentrations of nutrients were measured. Mean caloric intake was 29.4 (SD 10.7) kcal/kg; 24 (75%) patients had lower energy intakes than recommended for normals. Protein, vitamin C and folate intakes were above recommended minimum safe intakes. Intakes were less than recommended for calcium in four (13%) patients, iron in one (3%) and vitamin B12 in two (6%). One-third of both sexes had body mass indices (kg/m2) less than 25th percentile for normals, but none was less than 80% of ideal bodyweight. Arm muscle circumference was less than 10th percentile for normals in six men and three women. Triceps skin fold thickness was less than 10th percentile in four men (17%) and five women (55%). No anthropometric measurements were correlated with energy, protein or fat intake. Biochemical measurements were not useful in predicting protein intake. Neither nutritional intake nor anthropometric measurements were correlated with the duration of HHD. There was little evidence of malnutrition and wasting in this group of well rehabilitated HHD patients.

Adult

The association of infantile osteopetrosis and neuronal storage disease in two brothers.

Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms included blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumulation of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction.

Brain

Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain.

Frozen brain specimens from eight multiple sclerosis (MS) patients were examined for the presence of leukocytes and their cell products by using a panel of monoclonal antibodies. The results presented here demonstrated that in the MS lesion, there was a marked accumulation of HLA-Dr-positive (Ia-positive) cells. These Ia-positive cells were identified as being glial fibrillary acidic protein positive by using double staining methods. Furthermore, the cells in the MS lesion expressed the interleukin 2 (IL 2) receptor, as identified by the anti-TAC monoclonal antibody. The cells in the region of the plaque also exhibited positive staining with antibodies to IL 1, IL 2, and prostaglandin E. Neither normal brain nor brain specimens from progressive multifocal leukoencephalopathy or Alzheimer's disease showed such patterns of staining. These results suggest that stimulated cells are present in the MS brain, thus implicating an active immune mechanism in the pathogenesis of MS.

Adolescent

Trends in blood lead levels in Christchurch (NZ) and environs 1978-85.

Blood lead levels have been monitored since 1974 and have shown a significant decrease (p less than 0.001) from 1978 to 1985 in 2830 subjects from Christchurch and environs. From a baseline in August 1978-81 to August 1985 blood lead levels in a population which had no relevant exposure to lead other than that from the general environment have fallen in adult males and females (greater than 17 years) by 42%, and in school and pre-school children greater than 9 months by 44% and 46% respectively. Reduction of blood lead has accelerated during the last three years. This can be linked to changes in dietary intake and clean up of lead in domestic and industrial environments. Over this decade the lead content of petrol (0.84 g/l) and petrol sales have remained unchanged.

Adolescent

Diurnal patterns of blood pressure, heart rate and vasoactive hormones in normal man.

In order to determine arterial pressure and vasoactive hormone relationships in normotensive man, we measured intra-arterial pressure continuously along with hourly venous hormone levels (renin, angiotensin II, aldosterone and catecholamines) for 24 hours in 5 healthy volunteers under standardized conditions. Mean 24-hour levels of intra-arterial pressure 106/63 +/- 5.4/4.9 mmHg were much lower than in patients with mild essential hypertension studied earlier. A common diurnal pattern was seen for plasma renin, angiotensin II, and catecholamines, with higher levels in the day time and lower levels at night. Aldosterone levels however, paralleled those of cortisol at night. Plasma norepinephrine levels showed close, positive correlations with arterial pressure in all volunteers. We conclude that the level of blood pressure as measured continuously over 24 hours is lower than might be expected from regular clinic recordings; that aldosterone regulation is contributed to by ACTH in the nocturnal hours; and that fluctuations in arterial pressure and sympathetic activity over 24 hours are closely coupled.

Adult

Teamwork can improve the health of lead process workers.

A team working co-operatively to improve the health of lead workers has evolved over the last 10 years. We have monitored 704 employees for red cell lead (4800 samples) from a factory since 1974. In 1975, 32 employees, one-third of the workforce were suspended at a red cell lead level of greater than 10.7 mumol/l. Since 1980 no-one has been suspended at the current lower level of 7.7 mumol/l. By June 1984 the red cell lead mean for all process areas is less than 4.5 mumol/l (average 3.6 mumol/l). In 1984 the usual red cell lead range for local non-industrially exposed adult males is 1.23 SD 0.65 mumol/l. The value of cumulative reporting and contributory factors in reducing the blood levels are discussed.

Adult

Industrial lead exposure: a review of blood lead levels in South Island industries, 1974-83.

Relative risks of increased lead absorption found in 31 occupations were investigated. Serial red cell lead measurements on 1319 males and 186 females provided a mean and range for each occupational type. The magnitude of the mean and percentage of raised levels identified the degree of occupational risk. The mean red cell lead for 50% of employees was within the regional usual range for those not occupationally exposed. In 77% the mean red cell lead was less than 4.1 mumol/l. Of the remainder, 4% had levels greater than 5.7 mumol/l and 1% had levels greater than 7.7 mumol/l. Our findings have been used to manage local chronic and acute lead problems.

Erythrocytes

Neurochemical abnormalities in a patient with ataxia-telangiectasia.

We describe biochemical abnormalities found in autopsied brain of a patient with ataxia-telangiectasia. Neuropathologic changes were limited to the cerebellum and spinal cord. The atrophic cerebellum showed marked loss of Purkinje's and granule cells, and moderate loss of stellate and basket cells. Glutamic acid content was markedly reduced, and taurine content somewhat reduced in the cerebellar cortex, while gamma-aminobutyric acid (GABA) content was greatly reduced in the dentate nucleus. GABA receptor binding was reduced by 70% in cerebellar cortex. Phosphoethanolamine content was greatly reduced in the cerebellar cortex and inferior olivary nucleus. This compound was also deficient in 10 other brain regions and was the only extracerebellar neurochemical abnormality observed.

Ataxia Telangiectasia

Steroid receptors in meningiomas. A histochemical and biochemical study.

Meningiomas are more common in females and their course can be affected by changes in the hormonal milieu of the patient. Recently, a few studies have reported the presence of one or more steroid receptors in a small number of meningiomas. We have studied the estrogen and progesterone receptors (ER and PgR) of 11 surgically excised meningiomas. The receptors were assayed biochemically and localized at the cellular level using fluoroceinated estradiol and rhodamine-conjugated progesterone. Considerable amounts of ER were found in 4/11 cases, and PgR was high in 6/11 tumors. Cytoplasmic localization of the steroid binding sites was seen using both tracers. The presence of 10% of cells with two ++ intensity of the fluorescence correlated with tumors having positive ER values (greater than 10 Fm/mg protein). The presence of nuclear fluorescence and the higher level of PgR seen in some tumors indicate that the ER present is functioning. This study confirms the presence of steroid binding sites in meningiomas and suggests that there may be a role for hormonal manipulation in selected patients.

Adult

Primitive neuroectodermal tumors of the central nervous system.

Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Under the designation primitive neuroectodermal tumors are included medulloblastomas and tumors that may differentiate in other directions, such as medulloepithelioma, neuroblastoma, polar spongioblastoma, pineoblastoma, ependymoblastoma, retinoblastoma, and olfactory neuroblastoma. From a practical, histologic point of view, these tumors are often indistinguishable from one another and are best thought of as primitive neuroectodermal tumors with or without differentiating features.

Animals