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Biomedical subjects

N Howell

Publications and source records attributed to N Howell.

97 records · Page 6Linked to original sources
PubMed1971

Mitochondrial biogenesis in Neurospora crassa. I. An ultrastructural and biochemical investigation of the effects of anaerobiosis and chloramphenicol inhibition.

The isolation of a new class of mutants permitting facultative anaerobiosis in Neurospora crassa is described. Backcross analyses to the obligate aerobe prototroph (An(-)) indicate single nuclear gene inheritance (An(-)/An(+)). An(+) and An(-) are indistinguishable in morphology and growth rates under aerobic conditions. Anaerobic growth requires nutritional supplements that are dispensable for aerobic growth. Conidiogenesis, conidial germination, and vegetative growth rate are suppressed by anaerobiosis. An(+) mutants produce substantial quantities of ethanol under anaerobic conditions. Anaerobiosis and chloramphenicol both affect mitochondrial enzyme activity and morphology. Chloramphenicol inhibition leads to reduction in cytochrome oxidase and swollen mitochondria with few cristae. Anaerobiosis leads to reduction in both cytochrome oxidase and malate dehydrogenase activities, enlarged mitochondria with fewer cristae, enlarged nuclei, and other alterations in cellular morphology. The fine structure of anaerobically grown cells changes with the time of anaerobic growth. We conclude that either inhibition of mitochondrial membrane synthesis or inhibition of respiration might lead to the observed alterations in mitochondria.

Aerobiosis↗
PubMedDate not supplied

Mitochondrial gene segregation in mammals: is the bottleneck always narrow?

The segregation of a heteroplasmic silent polymorphism in the mitochondrial ND6 gene has been followed in a human maternal lineage comprising eight individuals and spanning three generations. Heteroplasmy persisted in all eight maternally related family members. More importantly, the frequencies of the two alleles showed relatively little variation among individuals or between generations. In contrast to the findings in other mammalian lineages, the present results indicate relatively slow mitochondrial gene segregation. A narrow bottleneck in the number of mitochondrial DNA (mtDNA) molecules, which occurs at some stage of oogenesis, has been advanced to explain rapid mammalian mitochondrial gene segregation. It is suggested here that the segregation of mitochondrial genes may be more complex than initially envisaged, and that models need to be developed that account for both rapid and slow segregation. One possibility, which reconciles both physical and genetic studies of mammalian mtDNA, is that the unit of mitochondrial segregation is the organelle itself, each containing multiple mtDNA molecules.

Alleles↗
PubMedDate not supplied

Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells.

Mammalian cells selected for resistance to certain cytotoxic drugs frequently develop cross-resistance to a broad spectrum of other drugs unrelated in structure to the original selective agent. This phenomenon constitutes a major problem in cancer chemotherapy. Multi-drug resistance arises from decreased intracellular drug accumulation, apparently due to an alteration of the plasma membrane. The observation of double minute chromosomes or homogeneously staining regions in some of the multi-drug-resistant cell lines suggests that gene amplification underlies this phenomenon. We have used the technique of DNA renaturation in agarose gels to detect, compare and clone amplified DNA sequences in Adriamycin- and colchicine-resistant sublines of Chinese hamster cells. We show that both Adriamycin- and colchicine-resistant cells contain amplified DNA fragments, some of which are amplified in both of these independently derived cell lines. Furthermore, loss of the multi-drug resistance phenotype on growth in the absence of drugs correlates with the loss of amplified DNA. These results strongly suggest that the DNA sequences which are amplified in common in multi-drug-resistant cell lines include the gene(s) responsible for a common mechanism of multi-drug resistance in these cells. We have cloned one of the commonly amplified DNA fragments and show that the degree of amplification of this fragment in the cells correlates with the degree of their drug resistance.

Animals↗
PubMedDate not supplied

Accuracy or bias in nurses' ratings of patient compliance: a comparison of treatment modality.

OBJECTIVE: The study examined the accuracy of nurses' assessments of patient compliance and identified factors influencing these assessments, including possible biases. DESIGN: Nurses' assessments of compliance, lab serum levels of dietary compliance, and interdialytic weight gain (IWG) were collected and compared to each other. End-stage renal disease (ESRD) patients on peritoneal dialysis (PD) and hemodialysis (HD) were compared on these measures and their compliance. SETTING: The study was conducted at the tertiary care university hospital at Stony Brook. PATIENTS: Data were collected for 62 ESRD patients (38 male, 24 female; mean age 54 years). The sample consisted of 26 HD and 36 PD patients. INTERVENTIONS: Nurses rated patients' compliance with fluid restrictions (HD patients only) and overall dietary compliance, as well as individual indicators of compliance including protein, potassium, and phosphorus compliance on a 7-point rating scale. Interdialytic weight gain, dietary (serum BUN and K levels), and medication compliance were recorded from charts for a 3-month period for each patient. MAIN OUTCOME MEASURES: The main outcome measures were the correlations between nurses' ratings of compliance and medical compliance data and the regression coefficients, which indicate the relative importance of each of the factors that nurses use to make their compliance ratings. RESULTS: Nurses' ratings for patients in both treatment modalities were highly correlated with the medical data for measures of fluid (r = 0.66, p < 0.001), potassium (r = 0.36, p < 0.01), and phosphorus (r = 0.36, p < 0.01). A regression analysis indicates that potassium (beta = 0.48, p < 0.001), phosphorus (beta = 0.19, p < 0.05), and protein (beta = 0.31, p < 0.01) all significantly contributed to nurses' assessments of patients' overall compliance. However, nurses' ratings of education levels for patients in both treatment modalities were not associated with phosphorus (r = 0.07, p < 0.61), protein (r = 0.18, p < 0.23), or potassium (r = 0.03, p < 0.85) measures. Finally, regressions revealed that nurses used personal knowledge of the patients when rating noncompliant patients (beta = 0.49, p < 0.05) but not when rating compliant patients (beta = 0.05, p < 0.75). CONCLUSIONS: Nurses rely heavily on medical records to rate patients' compliance and to make accurate assessments. Nurses also use several individual indicators (lab values and IWG) to rate overall dietary compliance, suggesting a thorough assessment. While assessments are not biased by personal factors such as nurses' perceptions of patients' education levels, nurses do rely on personal knowledge when rating noncompliant patients.

Adult↗