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Biomedical subjects

A Hebert

Publications and source records attributed to A Hebert.

15 recordsLinked to original sources
PubMed1999

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

Animals↗
PubMed1998

Glaucoma's impact on quality of life and its relation to clinical indicators. A pilot study.

OBJECTIVE: This study aimed to compare the quality of life (Q of L) of patients with glaucoma and control subjects and to determine the relationships between Q of L and demographic and clinical variables in patients with glaucoma. DESIGN: The study design was a stratified cross-sectional study. PARTICIPANTS: A gender-, race-, and age-stratified cross-sectional sample of patients with glaucoma (n = 56) and control subjects (n = 54) was obtained. Additional patients (n = 12) were included to examine the relationships between glaucoma, its therapy, and Q of L. INTERVENTION: The Medical Outcomes Study short form (MOS-20), the Activities of Daily Vision Scale (ADVS), and questions related to glaucoma and side effects of treatment were administered. Descriptive statistics characterized demographic variables and MOS and ADVS scales. Group differences were evaluated using chi-square, Fisher's and Ordinal Exact, Wilcoxon rank-sum, and two-sample t tests. Spearman rank correlations were obtained between MOS-ADVS scores and clinical and demographic variables. Regression was used for multivariate analysis. MAIN OUTCOME MEASURES: The MOS scores, ADVS scores, visual acuity, visual fields, and demographic variables were measured. RESULTS: Patients scored significantly lower than did the control subjects in all MOS-20 categories except pain. Differences were physical (-20%), role (-43%), mental health (-10%), general health (-22%), and social (-9%). The only category that was not statistically significant was that of pain (P = 0.075). In the glaucoma subgroup, there were differences between whites and nonwhites in MOS subscales physical, role, social, pain, and health, and ADVS near vision. In patients, current medications and previous surgeries correlated with ADVS subscales night vision, near vision, and glare; visual acuity and fields correlated with MOS subscales physical, role and health, and all ADVS subscales. A multiple regression model including visual acuity and fields, urban residence, and female gender explained 61% of the variability in ADVS overall score. CONCLUSIONS: The Q-of-L perception differed between patients with glaucoma and control subjects. Increasing field loss, decreased visual acuity, and complexity of therapy correlated with patients' reduction in activities of daily vision.

Activities of Daily Living↗
PubMed1998

[Quality of data acceptable for perinatal epidemiology surveillance: assessment of the health certificate at birth and the national obstetrics medical file. Study in three Seine-Maritime maternal wards].

Data from several sources could be used for perinatal epidemiology surveillance aimed at an assessment of regional programs such as those proposed by the Superior Committee for Public Health. A retrospective study of 561 births was conducted in three maternity wards in the French Seine Maritime department in order to evaluate the reliability of two data sources: the national obstetrics medical file and the health certificate at birth. The delivery room records were used as the gold standard. The sensitivity of the obstetrics file was better than that of the health certificate. With the obstetrics file, it was possible to identify almost all the vaginal route interventions, almost all the premature births and all the cesareans. With the health certificate, 39-58% of the vaginal route interventions, 61% of the premature births and 61-72% of the cesareans performed in the three wards studied were identified. The quality of data in the obstetrics file appears to be better than that in the health certificate but only concerns 40% of births in the geographical area studied. Inversely, the health certificate is theoretically delivered for all births (actually delivered for 93%). Integrating these two information systems could be an optimum solution.

Bias↗
PubMed1993

A driving program for the visually impaired.

This driving program for the visually impaired individual was devised in 1986, as a specific adjunct to the pre-existing training program, designed for the cognitive and physically impaired patients. Two important purposes of the program are: 1) To give the low vision practitioner and staff the capability to be able to recommend a specific training program for telescopic and visually impaired drivers. 2) To try to ensure that every visually impaired telescopic driver (prescribed with a telescopic system by the low vision center) would not only meet legal visual acuity and visual field requirements for the State of Michigan, but would also improve the competency of using their telescopic system for driving.

Automobile Driver Examination↗
PubMed1992

Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical phenotypes.

Two siblings are described whose clinical presentation of cutaneous photosensitivity and central nervous system dysfunction is strongly reminiscent of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum. An extensive clinical evaluation supported a diagnosis of DCS and documented previously unreported findings. In vitro fibroblast studies showed UV sensitivity that was two to three times that of normal controls. However, neither a post-UV-irradiation DNA excision-repair defect indicative of XP nor a semiconservative DNA replication defect indicative of XP variant was found. Rather, a failure of RNA synthesis to recover to normal levels after UV exposure was observed, a biochemical abnormality seen in Cockayne syndrome (CS), one of the premature-aging syndromes with clinical UV sensitivity. These patients, therefore, clinically have XP, but their biochemical characteristics suggest CS. The reason(s) for the severe neurologic disease, in light of the relatively mild cutaneous abnormalities, is unclear. Other cases with unusual fibroblast responses to irradiation have been noted in the literature and, along with the data from our patients, reinforce the notion of the complexity of DNA maintenance and repair.

Child↗
PubMed1991

Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses.

Previously we demonstrated that transgenic mice expressing mutant basal epidermal keratin genes exhibited a phenotype resembling a group of autosomal dominant human skin disorders known as epidermolysis bullosa simplex (EBS). EBS diseases affect approximately 1: 50,000 and are of unknown etiology, although all subtypes exhibit blistering arising from basal cell cytolysis. We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes. To demonstrate function, we engineered one of these point mutations in a cloned human K14 cDNA, and showed that a K14 with an Arg-125----Cys mutation disrupted keratin network formation in transfected keratinocytes and perturbed filament assembly in vitro. Since we had previously shown that keratin network perturbation is an essential component of EBS diseases, these data suggest that the basis for the phenotype in this patient resides in this point mutation.

Amino Acid Sequence↗
PubMed1986

Hormonal regulation of testicular human chorionic gonadotropin binding and steroidogenesis in adult mice with different forms of hereditary diabetes and obesity.

The regulation of testicular hCG binding and steroidogenesis in adult mutant mice with hereditary diabetes and obesity was studied. Low doses of hCG caused no change in hCG binding in obese (ob/ob) mice, whereas, in diabetic (db/db) mice, the increase in binding measured 24 h after hCG administration was not as great as in normal males. Intermediate doses of hCG caused a decrease in hCG binding in obese and normal mice, but not in diabetic animals. However, 72 h after injection of intermediate doses of hCG, a decrease in hCG binding also was observed in diabetic mice. Plasma testosterone was elevated 24 h after hCG injection in all types of mice studied, but the increase in diabetic mice was smaller than in normal animals. However, 72 h after treatment with hCG, plasma testosterone was still elevated in diabetic mice, but not in normal males. In vitro, hCG stimulated testicular testosterone synthesis in all groups of mice, but the observed increase was smaller in diabetic and obese than in normal animals. Plasma LH levels were higher in diabetic than in normal mice, whereas plasma FSH and prolactin levels were lower in obese mice than in normal animals. All parameters (i.e., LH receptors and circulating hormone levels) measured in yellow (Ay/a) mice were similar to those in normal (a/a) mice. The present study indicates that in these models for noninsulin-dependent diabetes, the testicular metabolism of LH receptors and capacity to secrete steroids is altered.

Animals↗
PubMed1985

Orf. A case report with histologic, electron microscopic, and immunoperoxidase studies.

Orf is an occupational skin disease acquired through contact with infected animals. In humans, orf is usually a self-limited disease that resolves spontaneously within four to 24 weeks. We report a case with multiple lesions of orf, acquired by contact with a wild sheep. The patient was temporarily immunosuppressed by a concomitant viral hepatitis. We reviewed the histologic and electron microscopic findings. Also, we attempted to stain the Parapoxvirus in the skin of the patient, using the immunoperoxidase technique. The antiserum was obtained from sheep immunized against orf. We used lesional skin from sheep infected with orf as a positive control. The negative results of this technique in the patient's skin indicated that Parapoxvirus infecting wild sheep is antigenically different from that causing the disease in domestic animals.

Animals↗
PubMed1984

Does prolactin modify testosterone feedback in the hamster? Pituitary grafts alter the ability of testosterone to suppress luteinizing hormone and follicle-stimulating hormone release in castrated male hamsters.

Adult male golden hamsters maintained in a long photoperiod (14 h of light and 10 h of darkness) or in a short photoperiod (5 h of light and 19 h of darkness for 7 weeks) were castrated and either given one anterior pituitary transplant under the kidney capsule or sham-operated. Additional animals were castrated and grafted or sham-grafted at the time of transfer to the short photoperiod. Starting 2 weeks after castration, all animals were injected three times a week with 20 micrograms testosterone propionate (TP). After 3 weeks, the dose of TP was increased to 80 micrograms and, after an additional 2 weeks, to 320 micrograms per injection. Blood samples were collected 2 weeks after castration and 1 day after the last injection of 20, 80, and 320 micrograms TP. Short photoperiod reduced and pituitary grafts increased plasma PRL levels. Plasma testosterone levels were related to the dose of injected TP, but were not influenced by photoperiod or pituitary transplants. Before the onset of TP injections, plasma LH and FSH levels in grafted and sham-grafted hamsters did not differ. In each of the three photoperiod conditions, injections of TP were consistently less effective in suppressing plasma gonadotropin levels in pituitary-grafted animals than in sham-grafted controls. These results indicate that PRL modulates the effects of exogenous testosterone on LH and FSH release in adult castrated male golden hamsters, this effect of PRL is due to reducing the sensitivity of the hypothalamic-pituitary system to feedback inhibition by testosterone, and suppression of pituitary PRL release in short photoperiod may be partially responsible for the concomitant increase in the sensitivity of LH and FSH release to inhibition by testosterone.

Animals↗
PubMed1984

Does prolactin modify testosterone feedback in the hamster? Suppression of plasma prolactin inhibits photoperiod-induced decreases in testosterone feedback sensitivity.

The hormonal changes during the photoperiodically driven annual reproductive cycle of the male golden hamster can be explained partially by a change in the sensitivity of the hypothalamo-pituitary axis to negative feedback by testosterone (T). The present studies test the hypothesis that the increases in plasma levels of LH and FSH that follow photo-stimulation are due to decreasing feedback sensitivity and examine if this change in sensitivity is dependent upon increasing PRL levels. Adult males were exposed to a lighting schedule of 5 h of light, 19 h of darkness (5:19) for 12 weeks to induce gonadal regression. The animals were castrated; treated with an inhibitor of PRL release, bromocriptine (CB-154), or oil; and received a Silastic capsule that was empty or filled with T. Subsequently, the animals were transferred to 14:10 and killed 9 or 31 days later. There were no significant changes in FSH and LH in animals receiving oil injections and empty implants between days 9 and 31, suggesting no steroid-independent changes in gonadotropin secretion during this time period. However, 4-mm T implants were more effective in suppressing LH and FSH levels on day 9 than on day 31. This suggests that there is a gradual decrease in feedback sensitivity to T following photostimulation. T was more effective in inhibiting LH and FSH levels in CB-154-treated than in oil-treated animals on both day 9 and day 31. Thus, increases in PRL release are instrumental in causing decreases in feedback sensitivity following photostimulation.

Animals↗
PubMed1973

Hypoxanthine-guanine phosphoribosyltransferase variant associated with accelerated purine synthesis.

We have previously described a 14-yr-old boy with hyperuricemia, renal failure, and accelerated purine production resistant in vivo and in vitro to purine analogs. This patient demonstrated normal red cell hypoxanthine-guanine phosphoribosyltransferase (HPRT) heat stability, electrophoresis at high pH, and activity at standard substrate levels. In the present report an abnormal HPRT enzyme was demonstrated by enzyme kinetic study with phosphoribosylpyrophosphate (PRPP) as the variable substrate and inhibitory studies with sodium fluoride. Apparently normal HPRT activity in a patient with hyperuricemia and gout does not exclude a functionally significant HPRT mutation.

Adolescent↗