A new subtype of diabetes mellitus: maternally inherited diabetes and deafness (MIDD)

Diabetes mellitus comprises many subtypes, the pathogenesis of each of which involves a combination of inherited and environmental factors. Recently a new subtype of diabetes mellitus was recognized in a Dutch pedigree, designated as 'maternally inherited diabetes and deafness' (MIDD). Impaired hearing is an associated phenomenon of the disease. Approximately 1.3% of all diabetic cases in the Netherlands exhibit the MIDD subtype. MIDD shows a strictly maternal heredity. In MIDD there is a guanine-for-adenine substitution at position 3243 in mitochondrial DNA. Mitochondria carrying this mutation exhibit a decreased functionality. In carriers of the MIDD mutation the insulin secretion by the pancreas in response to stimulation by glucose is impaired.     

Adult brainstem gliomas

OBJECTIVE: To evaluate prognostic factors and survival of adult patients with brainstem gliomas. BACKGROUND: Brainstem glioma is a disease found primarily in children, with a median survival of only 9 to 12 months. However, the prognosis and survival of adults with this disease has not been determined with precision. METHODS: We conducted a retrospective analysis of patients older than 16 years at Memorial Sloan-Kettering Cancer Center with histologically proved or presumed brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of gender, age at diagnosis, cranial nerve involvement, duration of symptoms, exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky performance status on survival. RESULTS: Twenty-three patients were identified, but complete information was available in only 19 (12 males and 7 females). Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients were treated with radiotherapy at diagnosis and seven were observed, three of whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to 98 months) and the 5-year survival is 45%. There was a trend for patients with a higher performance status at diagnosis to have longer survival, but this did not reach statistical significance. Other factors did not affect survival. CONCLUSION: Adults with brainstem gliomas may survive significantly longer than children, suggesting the disease may be less aggressive in adults. Furthermore, some patients with a long duration of symptoms or tectal or cervicomedullary tumors may be managed initially with observation alone.     

High-flow bypass using nonocclusive excimer laser-assisted end-to-side anastomosis of the external carotid artery to the P1 segment of the posterior cerebral artery via the sylvian route. Technical note

In a patient with a giant aneurysm of the basilar artery trunk, a vein graft was interposed between the external carotid artery in the neck and the P1 segment of the posterior cerebral artery. Balloon occlusion of both vertebral arteries was performed 3 days later. The sylvian route was used for the grafting procedure and the connection to the posterior cerebral artery was made by using the excimer laser-assisted nonocclusive anastomosis technique.     

Differing effects of endogenous and synthetic inhibitors of metalloproteinases on intestinal tumorigenesis

The strength of the radius depends on the mechanical properties of cancellous and cortical bone. By assessing both compartments quantitatively with bone densitometry, we tried to identify the specificity of each in predicting the load at which the distal radius will fracture. Twenty human cadaver forearms were scanned for bone mineral and geometric properties with quantitative computed tomography and dual x-ray absorptiometry. In both a neutral loading situation and one in which the wrist was extended 45 degrees, the load distribution was determined with pressure-sensitive films, and a fracture simulating a fall on the hand was produced with a material testing machine. Fractures that occur with the wrist in extension were produced by a central impact of the scaphoid onto the radiocarpal joint, and those that occur under neutral loading conditions were produced by a more commonly distributed loading pattern. The load at fracture was most specifically predicted (r2=0.74) by bone mineral and geometric measures of the cortex at the shaft of the radius. Bone mineral density measures of trabecular (r2=0.64) and total (r2=0.66) bone were less successful in predicting the fracture load. After adjustment for bone size, the geometric and density measures revealed similar specificity. Cortical bone, therefore, contributes significantly to the strength of the distal radius and may play an important role in the prediction of osteoporotic wrist fractures.     

Opposing actions of prostaglandins and oxytocin determine the onset of murine labor

Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2alpha production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2alpha production. These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.     

Differential membrane localization and intermolecular associations of alpha-dystrobrevin isoforms in skeletal muscle

alpha-Dystrobrevin is both a dystrophin homologue and a component of the dystrophin protein complex. Alternative splicing yields five forms, of which two predominate in skeletal muscle: full-length alpha-dystrobrevin-1 (84 kD), and COOH-terminal truncated alpha-dystrobrevin-2 (65 kD). Using isoform-specific antibodies, we find that alpha-dystrobrevin-2 is localized on the sarcolemma and at the neuromuscular synapse, where, like dystrophin, it is most concentrated in the depths of the postjunctional folds. alpha-Dystrobrevin-2 preferentially copurifies with dystrophin from muscle extracts. In contrast, alpha-dystrobrevin-1 is more highly restricted to the synapse, like the dystrophin homologue utrophin, and preferentially copurifies with utrophin. In yeast two-hybrid experiments and coimmunoprecipitation of in vitro-translated proteins, alpha-dystrobrevin-2 binds dystrophin, whereas alpha-dystrobrevin-1 binds both dystrophin and utrophin. alpha-Dystrobrevin-2 was lost from the nonsynaptic sarcolemma of dystrophin-deficient mdx mice, but was retained on the perisynaptic sarcolemma even in mice lacking both utrophin and dystrophin. In contrast, alpha-dystrobrevin-1 remained synaptically localized in mdx and utrophin-negative muscle, but was absent in double mutants. Thus, the distinct distributions of alpha-dystrobrevin-1 and -2 can be partly explained by specific associations with utrophin and dystrophin, but other factors are also involved. These results show that alternative splicing confers distinct properties of association on the alpha-dystrobrevins.     

Feminism: a perspective for the 21st century

This article details some of the key elements related to feminism in American society. It suggests that the meaning and significance of a feminist perspective need to be reexamined for their importance and utility in this dynamic and rapidly changing society. A discussion of the meaning of feminism provides a framework for the article. Issues related to cultural diversity and the need for competent health care delivery for all people are some major themes. The other emphasis is related to research and women. Numerous challenges are outlined. A feminist perspective is recommended as a conceptual model through which health care reform can be enhanced. If feminism were embraced, the health status of people would be improved.