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Biomedical subjects

G Howe

Publications and source records attributed to G Howe.

At least 37 records · Page 2Linked to original sources
PubMed1994

Role of heme in the biosynthesis of cytochrome c6.

Cytochrome c6, a nuclear-encoded protein, is synthesized in the cytoplasm in a precursor form (pre-apocytochrome c6). Time course radiolabeling experiments support the model that the pre-protein is the substrate for a lumen-targeting post-translational pathway which includes two proteolytic cleavage events and the covalent attachment of heme to cysteinyl thiols on the polypeptide. Cell fractionation studies indicate that the fully processed protein fractionates with other soluble proteins, whereas the precursor and intermediate forms appear to be membrane-associated. To determine whether either of the processing steps is influenced by heme attachment, the biosynthetic pathway was examined 1) in a Chlamydomonas reinhardtii mutant (B6) that is defective in the heme attachment step and 2) in wild-type cells treated with gabaculine, an inhibitor of heme synthesis. In vivo radiolabeling experiments with the B6 mutant showed that a defect in heme attachment affects neither the synthesis of the pre-apoprotein nor its processing to the mature apoform to any significant extent, supporting the notion that heme attachment and processing are not obligatorily coupled in this pathway. A similar conclusion is reached from examination of cytochrome c6 synthesis in gabaculine-treated cells where inhibition of heme attachment did not prevent either of the two processing steps. The fully processed apoprotein is a suitable substrate for heme attachment in vivo, since the apoprotein was indeed converted to holoprotein in gabaculine-treated cells, albeit more slowly than in untreated cells. Despite the lack of effect of gabaculine treatment on the accumulation of cytochrome c6-encoding messages, the amount of holocytochrome c6 precursors synthesized during a brief labeling period is 4-7-fold less than in untreated cells, suggesting that synthesis of the polypeptide may be coupled to heme availability by a control mechanism operating at the translational level.

Animals↗
PubMed1993

Maturation of thylakoid lumen proteins proceeds post-translationally through an intermediate in vivo.

Many thylakoid lumen proteins are synthesized outside the chloroplast as larger molecular weight precursors and then processed to their mature size during transport to the lumenal space. We have examined the post-translational processing of thylakoid lumen proteins in vivo by pulse-radiolabeling experiments with Chlamydomonas reinhardtii. Antibodies against the lumenal protein cytochrome c6 specifically immunoprecipitated three polypeptides from extracts of briefly pulse-radiolabeled cells. The molecular weights and kinetics of synthesis and turnover indicate that these three polypeptides are (i) the full-length cytochrome c6 precursor, (ii) a partially processed precursor (intermediate), and (iii) the completely processed mature protein. Identification of analogous forms of two other lumenal proteins, plastocyanin and the oxygen evolving enhancer 1 protein, indicates that the maturation of thylakoid lumen proteins occurs post-translationally in vivo and that the partially processed intermediate is a general feature of the pathway. The intermediate form of cytochrome c6 accumulated to a greater extent in cells incubated at 10 degrees C, relative to cells incubated at 22 degrees C, concomitantly with a decrease in the accumulation of the mature protein. The intermediate accumulating at 10 degrees C is quantitatively converted to the mature protein upon incubation at higher temperature, thus demonstrating a precursor-product relationship between the intermediate and mature forms of cytochrome c6. Our results prove the model [Smeekens, S., Bauerle, C., Hageman, J., Keegstra, K. & Weisbeek, P. (1986) Cell 46, 365-375] that precursors of lumenal proteins are post-translationally converted to their mature forms in two steps through a distinct intermediate.

Algal Proteins↗
PubMed1992

The biosynthesis of membrane and soluble plastidic c-type cytochromes of Chlamydomonas reinhardtii is dependent on multiple common gene products.

Cytochrome c6 functions in the thylakoid lumen to catalyze electron transfer from reduced cytochrome f of the cytochrome b6f complex to P700+ of photosystem I. The biogenesis of mature cyt c6 from cytosolically translated pre-apocytochrome c6 involves numerous post-translational modifications including the proteolytic removal of a transit sequence and the covalent attachment of heme to two cysteinyl thiols on the apoprotein. Here, we report on the characterization of a previously unrecognized class of non-allelic mutants of Chlamydomonas reinhardtii that are blocked at the conversion of apocyt c6 to holocyt c6. The mutants are acetate requiring since they are also deficient in cyt f, cyt b and the Rieske FeS protein. Pulse-chase studies indicate that heme attachment is not required for the two-step processing of pre-apocytochrome c6 to apocyt c6, but is required for the stability of the mature protein. This is in contrast to the biosynthesis of mitochondrial cyt c1 where heme attachment is required for the second processing step. We propose that the assembly of both holocytochrome c6 and the cytochrome b6f complex are dependent on common gene products, possibly those involved in heme delivery or metabolism. This is the first suggestion that multiple loci are involved in the biosynthesis of both plastidic c-type cytochromes.

Animals↗
PubMed1992

Heavy Metal-Activated Synthesis of Peptides in Chlamydomonas reinhardtii.

In this study, we have addressed the capacity of the green alga Chlamydomonas reinhardtii to produce metal-binding peptides in response to stress induced by the heavy metals Cd(2+), Hg(2+), and Ag(+). Cells cultured in the presence of sublethal concentrations of Cd(2+) synthesized and accumulated oligopeptides consisting solely of glutamic acid, cysteine, and glycine in an average ratio of 3:3:1. Cadmium-induced peptides were isolated in their native form as higher molecular weight peptide-metal complexes with an apparent molecular weight of approximately 6.5 x 10(3). The isolated complex bound cadmium (as evidenced by absorption spectroscopy) and sequestered (with a stoichiometry of 0.7 moles of cadmium per mole of cysteine) up to 70% of the total cadmium found in extracts of cadmium-treated cells. In Hg(2+)-treated cells, the principal thiol-containing compound induced by Hg(2+) ions was glutathione. It is possible that glutathione functions in plant cells (as it does in animal cells) to detoxify heavy metals. Cells treated with Ag(+) ions also synthesized a sulfur-containing component with a charge to mass ratio similar to Cd(2+)-induced peptides. But, in contrast to the results obtained using Cd(2+) as an inducer, these molecules did not accumulate to significant levels in Ag(+)-treated cells. The presence of physiological concentrations of Cu(2+) in the growth medium blocked the synthesis of the Ag(+)-inducible component(s) and rendered cells resistant to the toxic effects of Ag(+), suggesting competition between Cu(2+) and Ag(+) ions, possibly at the level of metal uptake.

Journal Article↗
PubMed1991

The association between alcohol and breast cancer risk: evidence from the combined analysis of six dietary case-control studies.

Data from 1,575 cases and 1,974 controls enrolled in 6 previously conducted case-control studies of diet and breast cancer have been analysed with respect to alcohol intake. There appears to be an absence of any association between consumption of up to 40 g of alcohol per day and risk of breast cancer, and a highly statistically significant and consistent elevated risk of breast cancer for drinkers of 40 g or more of alcohol per day, for whom the relative risk, as compared with that of non-drinkers, is 1.69 (95% confidence interval 1.19 to 2.40). This association is not due to confounding by a number of diet-related factors, including total calories, fat, fibre and vitamin C.

Adult↗
PubMed1991

Dynamic interplay between two copper-titrating components in the transcriptional regulation of cyt c6.

The algal plastidic cytochrome c (cyt c6) is a biochemical equivalent of the copper-containing protein plastocyanin in photosynthetic electron transfer. But generally, cyt c6 accumulates and functions only under conditions (e.g. Cu-deficiency) where holoplastocyanin cannot be synthesized. In studying the regulation of Chlamydomonas reinhardtii cyt c6 expression by Cu we have determined that repression of cyt c6 accumulation occurs at the transcriptional level, and specifically in response to Cu as the metal ion regulator. Complete and sustained repression of cyt c6 transcription requires approximately 9 x 10(6) Cu ions in the medium/cell. Based on the estimated plastocyanin content of algal cells (8 x 10(6) molecules/cell) and the observation that lower ratios of Cu per cell result in only transient repression of cyt c6 transcription, we propose that Cu-dependent transcriptional repression of the gene encoding cyt c6 requires a Cu-binding factor which is titrated by Cu only after the alternate electron transfer catalyst, plastocyanin, has accumulated to the stoichiometry required for photosynthesis. The precise and highly metal-specific, autoregulatory control of cyt c6 levels--directly by Cu, and indirectly by holoplastocyanin--is in keeping with the functional role of cyt c6 as an alternate, although perhaps less preferred, electron transfer catalyst.

Blotting, Northern↗
PubMed1989

A case-control study of diet and breast cancer in Argentina.

A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Argentina↗
PubMed1987

An investigation of patients presenting with multiple physical complaints using the illness behaviour questionnaire.

The Illness Behaviour Questionnaire was used to determine whether three groups of patients who had presented with multiple symptoms in different treatment settings (Briquet's syndrome, post-viral fatigue syndrome, and a heterogeneous general practice group) could be differentiated from one another and from a mixed group of psychiatric patients on the basis of their abnormal illness behaviour. All groups completed a version of the Perley and Guze diagnostic criteria for Briquet's syndrome. The three groups presenting with multiple symptoms were more similar to each other than to the psychiatric patients. The results suggest that patients presenting with multiple symptoms include similar populations of patients who are poorly distinguished using current schemes of classification.

Adult↗
PubMed1985

Effects of age, cigarette smoking, and other factors on fertility: findings in a large prospective study.

Of 17 032 women taking part in the Oxford Family Planning Association contraceptive study, 4104 stopped using a birth control method to plan a pregnancy on a total of 6199 occasions. The influence of various factors on fertility in these women was assessed by measuring the time taken to give birth to a child. An appreciable inverse relation was observed between age at stopping contraception and fertility both in nulliparous and parous women, but the effect was much greater in the nulliparous women. The most important finding was a consistent and highly significant trend of decreasing fertility with increasing numbers of cigarettes smoked per day; it was estimated that five years after stopping contraception 10.7% of smokers smoking more than 20 cigarettes a day, but only 5.4% of non-smokers, remained undelivered. Some relation was found between fertility and social class, age at marriage, and a history of gynaecological disease, but weight, height, and Quetelet's index were without noticeable effect.

Adult↗
PubMed1980

De Clerambault syndrome (erotomania): a review and case presentation.

A syndrome which was first described by G.G. De Clerambault in 1885 is reviewed and a case is presented. Popularly called erotomania, the syndrome is characterized by the delusional idea, usually in a young woman, that a man whom she considers to be of higher social and/or professional standing is in love with her. She develops an elaborate delusional process about this man, his love for her, his pursuit of her, and her inability to escape his "affectionate clutches." This syndrome may persist for a period of a few weeks to a few months in the recurrent form and be replaced by a similar delusion about another man. In the fixed form, which is the example of the case being presented here, it may persist for several years. The patient presented here has experienced this syndrome for eight years; there are reports in the literature of persons maintaining the syndrome for longer than 25 years.Patients with this syndrome may be diagnosed as having paranoid vera or other forms of paranoid disorder, or as paranoid schizophrenic. In light of the overwhelming nature of the delusional process affecting this patient's total life experience with marked delusions of persecution, grandeur, jealously, and self-depreciation as well as ideas of reference (illusions), and agitated and sometimes bizarre behavior, it seems quite appropriate that her diagnosis may be termed schizophrenic reaction, paranoid type.The literature is surveyed in depth and the case is presented in sequential detail.

Adult↗
PubMedDate not supplied

Adolescent, parent, and observer perceptions of parenting: genetic and environmental influences on shared and distinct perceptions.

Agreement among reporters on features of family life, whether family members or outside observers, is considered to be low. This study, which involved a national sample of 720 families comprised of identical and fraternal twins, full siblings, half siblings, and biologically unrelated stepsiblings, examined the issue of low interrater agreement by decomposing the common and unique variance among parent, child, and observer reports of parenting behaviors (warmth and negativity) into genetic and environmental factors. Quantitative genetic analyses were employed to decompose the "Social" level of perception (common variance among parents, children, observers), the level of "Family" subculture (common variance only among parents and children), and the unique "Individual" level into genetic and environmental components. It was predicted that genetic factors would account for substantial portions of the variance at the Social and Family levels; nonshared environmental factors were expected to influence variance unique to child reports; and shared environmental factors were expected to influence variance unique to parent reports. A second and related aim of the study was to examine the subjective-objective dimension of genetic effects on measures of the environment. Results of model-fitting analyses generally supported the predictions for parental warmth and negativity at the Family and Individual levels. At the Social level, genetic factors were predominant for parental negativity and shared environmental factors for parental warmth. The findings are discussed in terms of genetically influenced child effects on parenting and methodological difficulties in constructing latent variables.

Adolescent↗