Mas37p, a novel receptor subunit for protein import into mitochondria.

By screening a collection of Saccharomyces cerevisiae mutants temperature sensitive for growth on a nonfermentable carbon source, we have isolated a gene (termed MAS37) which encodes a novel receptor for protein import into mitochondria. Mas37p is a 37-kD outer membrane protein with two putative membrane-spanning regions. Inactivation of the MAS37 gene renders cells temperature-sensitive for respiration-driven growth, inhibits import of precursors into isolated mitochondria, and is synthetically lethal with a deletion of one of the genes encoding the import receptors Mas70p or Mas20p. Inactivation of Mas37p with specific antibodies inhibits import of different precursors to different extents; the precursor specificity of Mas37p resembles that of the previously described import receptor Mas70p. Mas70p and Mas37p form a 1:1 complex in detergent extracts of mitochondria and overexpression of one protein enhances that of the other. We suggest that the Mas37p/Mas70p heterodimer functions as a receptor for protein import into yeast mitochondria and that the mitochondrial receptor system consists of hetero-oligomeric subcomplexes with distinct binding activities, but overlapping precursor specificities.

Severe respiratory failure in neonates: mortality and morbidity rates and neurodevelopmental outcomes.

OBJECTIVE: To compare the survival, neurodevelopmental, and health outcomes of children with severe respiratory illness treated with and without extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective collection of clinical and demographic data of all neonates reaching illness severity criteria, with follow-up at 8 and 20 months of age. Patients were assigned to treatment by the attending physician. PATIENTS: Consecutive sample of 74 neonates during a 24-month period with an alveolar-to-arterial gradient exceeding 620 for 8 or more hours. RESULTS: Eighteen (69%) of 26 neonates treated with conventional therapy survived to 20 months, in comparison with 43 (90%) of 48 neonates treated with ECMO. The conventionally treated group had significantly more chronic lung disease, longer duration of oxygen therapy, more chronic reactive airway disease, and more rehospitalizations than those treated with ECMO. Hospital charges were similar in the two groups. Macrocephaly was noted in 24% of those treated with ECMO and in none of the conventional group. Of those completing evaluation, 4 (24%) of 17 conventionally treated survivors and 20 (26%) of 38 ECMO-treated survivors had neurodevelopmental impairment. CONCLUSION: Survivors of severe neonatal respiratory illness have significant pulmonary and neurodevelopmental impairment, regardless of the treatment used. Neonates treated with ECMO had neurodevelopmental outcomes similar to those of patients treated conventionally, but better pulmonary outcomes.

Late effects of poliomyelitis.

Muscular atrophy and decreased functional abilities are recognized as late complications of poliomyelitis. This study sought to more clearly define late-onset, postpolio muscular weakness--age of onset, symptoms, and severity--and to determine whether people might benefit from environmental modification, respiratory aids, and orthoses. A total of 183 postpolio patients were examined by a physician and completed a questionnaire on their ambulatory status and related musculoskeletal and respiratory symptoms. Of those participating in the study, 154 claimed to be experiencing late deterioration in strength. The syndrome included decreased endurance, more limited ambulation, and increased weakness in the previously affected limb/s. For those describing late-onset weakness, average ages were determined for the onset of polio (8.3 years), the onset of postpolio muscular weakness (42.3 years), and the latent period of stable functioning (34.8 years). Patients claimed to have experienced a new, lower level of strength for an average of 4.7 years. All 33 patients who had undergone muscle transfer surgery were experiencing late-onset weakness in that extremity. Fasciculations (51%) and long-bone fractures secondary to falls (21%) were common sleep disturbances occurred frequently (31%) even in those without prior bulbar involvement. Upper motor neuron signs were present in only one case. Bracing was rare (16%) and the braces used were usually old. The subjects did not report a steadily or rapidly progressive decline, but rather described a steplike decrement with long plateaus. The population described losses in strength that had significant bearing on functional status and general health.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracerebral hemorrhage in the full-term neonatal infant.

Supratentorial intracerebral hemorrhage was diagnosed in 18 full-term neonates, including six with primarily intraparenchymal hemorrhage and 12 with primarily intraventricular hemorrhage. Precipitating or associated factors were hypoxic-ischemic injury in five patients, polycythemia in two, and cranial birth trauma in two. Nine other infants had no identifiable medical risk events. The pathogenesis of intraparenchymal hemorrhage was probably related to hemorrhagic infarction, but the pathogenesis of intraventricular hemorrhage was often unknown. All 17 survivors returned for neurologic and developmental examinations between 1 and 7 years of age. Follow-up assessments were normal in nine children and abnormal in eight. Two had perceptual difficulties, three had moderate-to-severe cognitive deficiencies (two of the three had hemiplegia), and three had severe mental and neurologic handicaps. Eight of nine children with known or suspected hypoxic-ischemic or traumatic insults suffered moderate-to-severe disabilities whereas eight of nine children with no known precipitating cause for their hemorrhage developed normally.

Intellectual, neuropsychological, and achievement outcomes in children six to eight years after recovery from Haemophilus influenzae meningitis.

Twenty-four grade school children who had sustained an earlier episode of Haemophilus influenzae type b meningitis were tested, along with a group of 24 school-aged siblings. Evaluations consisted of tests of IQ, academic achievement, and neuropsychological skills. Parents completed forms rating each child's behavioral adjustment and temperament. Available school-administered standardized achievement tests were also obtained. Information relating to the episode of meningitis was extracted from the medical charts of each child who had had meningitis in order to investigate the relationship of these parameters to developmental outcome. Results showed that, compared with nearest-age siblings, children who had had meningitis scored lower on performance IQ and full-scale IQ. The group that had had meningitis also performed more poorly on several neuropsychological tasks. However, the groups did not differ in verbal IQ, and they performed comparably on all academic measures. Significant behavioral adjustment problems were absent from both groups, and there were no notable differences in temperament. Although findings support the existence of postmeningitis sequelae, the selective nature of the deficiencies observed indicate that prognosis for children in the age range examined may be better than that suggested by earlier studies.