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Biomedical subjects

N Hudson

Publications and source records attributed to N Hudson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Implications for therapy of drug-metabolizing enzymes in human colon cancer.

Human colonic tissue is exposed to a variety of toxic chemicals and potential carcinogens in the diet and the intestinal microenvironment. Colonic adenocarcinoma is commonly resistant to the cytotoxic effects of most chemotherapeutic drugs. We have examined drug metabolic and detoxification pathways in clinical specimens of colon carcinoma and normal adjacent mucosa from 17 patients. All elements of xenobiotic metabolism examined are present in these tissues, including cytochrome P-450-dependent enzymes, glutathione, and glutathione-utilizing enzymes. In comparison of tumor tissue to its respective normal mucosa specific alterations in the pathways affecting a number of chemotherapeutic agents were detected, including significantly higher glutathione, glutathione peroxidase, and anionic glutathione-S-transferase activity. These and other alterations found here could be the target of therapeutic maneuvers to enhance the efficacy of antineoplastic treatment of human colon cancer.

Adenocarcinoma↗
PubMed1989

Evaluating nursing productivity in child health.

As nurses are increasingly concerned with assessing and improving their productivity in a variety of settings, they must make systematic use of an evaluation model. The Discrepancy Evaluation Model (DEM) was used to evaluate the productivity of nurses in child health clinics in five centers in the southeastern United States. The first step in any evaluation is to identify standards against which performance can be measured. In this project, no standards were available, and creating them was the first task. Standards for productivity in child health were developed that accounted for differences in clients and the experience level of nurses, while maintaining quality of care. They were situation specific and allowed for the constraints operating in each of the five centers. Discrepancies between the standards and observed performance were identified and underlying factors examined, resulting in a number of recommendations that could streamline the provision of services and improve nursing productivity. The evaluation process can be applied to public health nursing services in a variety of settings.

Ambulatory Care Facilities↗
PubMed1987

Monoclonal antibody studies of creatine kinase. Antibody-binding sites in the N-terminal region of creatine kinase and effects of antibody on enzyme refolding.

(1) The binding sites of two monoclonal antibodies, CK-2A7 and CK-5H5, have been located to a 60-amino-acid sequence in the N-terminal region of creatine kinase (CK) by the use of chemical cleavage with formic acid (which cleaves proteins at Asp-Pro bonds) and cyanogen bromide (which cleaves at Met residues). (2) A simple method for preparing chemically-cleaved fragments of proteins for electrophoresis and Western blotting is described. (3) Binding studies with CK preparations from different animal species show that single amino acid changes at residues 39 or 82 prevent binding of CK-2A7 and CK-5H5 respectively. We suggest that Lys-39 and Glu-82 form parts of the binding sites on CK for the two monoclonal antibodies. The two sites lie in variable regions at each end of a highly-conserved sequence (residues 46 to 79) and are inaccessible to antibody in the native enzyme. (4) One of the antibodies, CK-2A7, inhibits the refolding of CK to native enzyme after denaturation by urea.

Amino Acid Sequence↗
PubMed1987

Differences in gonadotrophin concentrations and pituitary responsiveness to GnRH between Booroola ewes which were homozygous (FF), heterozygous (F+) and non-carriers (++) of a major gene influencing their ovulation rate.

The mean plasma concentrations of FSH and LH were significantly higher in FF ewes than in ++ ewes with those F+ animals being consistently in between. These gene-specific differences were found during anoestrus, the luteal phase and during a cloprostenol-induced follicular phase, suggesting that the ovaries of ewes with the F-gene are more often exposed to elevated concentrations of FSH and LH than are the ovaries of ewes without the gene. The gene-specific differences in LH secretion arose because the mean LH amplitudes were 2-3 times greater in FF compared to ++ ewes with the LH amplitudes for F+ ewes being in between. The LH pulse frequencies were similar. In these studies the pulsatile nature of FSH secretion was not defined. The pituitary contents of LH during the luteal phase, were similar in all genotypes whereas for FSH they were significantly higher in the F-gene carriers compared to ++ ewes. The pituitary sensitivity to exogenous GnRH (0.1, 0.5 and 25 micrograms i.v.) was related to genotype. Overall the LH responses to GnRH were lower in FF ewes than in ++ ewes with the results for the F+ ewes being in between. The FSH responses to all GnRH doses in the FF genotype were minimal (i.e. less than 2-fold). In the other genotypes a greater than 2-fold response was noted only at the highest GnRH dose (i.e. 25 micrograms). Treatment of FF and F+ but not ++ ewes with GnRH eventually led to a reduced FSH output, suggesting that the pituitary responses to endogenous GnRH were being down-regulated in the F-gene carriers whereas this was not the case in the non-carriers. Collectively these data confirm that peripheral plasma and the pituitary together with the ovary are compartments in which F-gene differences can be observed. In conclusion, these findings raise the possibility that F-gene-specific differences may also extend to the hypothalamus and/or other regions of the brain.

Animals↗
PubMed1986

Use of bovine follicular fluid to increase ovulation rate or prevent ovulation in sheep.

Romney ewes were injected intramuscularly once or twice daily for 3 days with 0, 0.1, 0.5, 1 or 5 ml of bovine follicular fluid (bFF) treated with dextran-coated charcoal, starting immediately after injection of cloprostenol to initiate luteolysis on Day 10 of the oestrous cycle. There was a dose-related suppression of plasma concentrations of FSH, but not LH, during the treatment period. On stopping the bFF treatment, plasma FSH concentrations 'rebounded' to levels up to 3-fold higher than pretreatment values. The mean time to the onset of oestrus was also increased in a dose-related manner by up to 11 days. The mean ovulation rates of ewes receiving 1.0 ml bFF twice daily (1.9 +/- 0.2 ovulations/ewe, mean +/- s.e.m. for N = 34) or 5.0 ml once daily (2.0 +/- 0.2 ovulations/ewe, N = 25) were significantly higher than that of control ewes (1.4 +/- 0.1 ovulations/ewe, N = 35). Comparison of the ovaries of ewes treated with bFF for 24 or 48 h with the ovaries of control ewes revealed no differences in the number or size distribution of antral follicles. However, the large follicles (greater than or equal to 5 mm diam.) of bFF-treated ewes had lower concentrations of oestradiol-17 beta in follicular fluid, contained fewer granulosa cells and the granulosa cells had a reduced capacity to aromatize testosterone to oestradiol-17 beta and produce cyclic AMP when challenged with FSH or LH. No significant effects of bFF treatment were observed in small (1-2.5 mm diam.) or medium (3-4.5 mm diam.) sized follicles. Ewes receiving 5 ml bFF once daily for 27 days, from the onset of luteolysis, were rendered infertile during this treatment period. Oestrus was not observed and ovulation did not occur. Median concentrations of plasma FSH fell to 20% of pretreatment values within 2 days. Thereafter they gradually rose over the next 8 days to reach 60% of pretreatment values where they remained for the rest of the 27-day treatment period. Median concentrations of plasma LH increased during the treatment period to levels up to 6-fold higher than pretreatment values. When bFF treatment was stopped, plasma concentrations of FSH and LH quickly returned to control levels, and oestrus was observed within 2 weeks. The ewes were mated at this first oestrus and each subsequently delivered a single lamb.

Animals↗
PubMed1985

An interaction between season of calving and nutrition on the resumption of ovarian cycles in post-partum beef cattle.

Angus cows were first mated at approximately 27 months of age in 2 herds, calving 21 July to 15 September (Group E) or 9 September to 30 October (Group L). The cows were fed a high (H) or medium (M) plane of nutrition for 55 days before and 40 days after calving. There was a mean liveweight difference of 35 kg between cows in Groups EH + LH and Groups EM + LM immediately after calving and at 40 days after calving. Immediately after calving cows in Groups EH + EM were 11 kg heavier than cows in Groups LH + LM, but there was no difference at 40 days after calving. There was a significant interaction between calving time and nutrition in the return of cyclic ovarian function assessed from both interval to first oestrus and first elevated progesterone concentration. Mean intervals from calving to first oestrus were 66.7, 82.7, 56.7 and 62.3 days in Groups EH, EM, LH and LM respectively. These data demonstrate that season of calving influences resumption of ovarian cycles even at a constant high plane of nutrition and that season of calving interacts with nutrition such that effects of season are more likely to be expressed under conditions of low nutrition.

Anestrus↗
PubMed1985

FSH influences follicle viability, oestradiol biosynthesis and ovulation rate in Romney ewes.

Injection of steroid-free bovine follicular fluid (bFF; 2 X 5 ml s.c. 12 h apart) into anoestrous ewes lowered plasma FSH concentrations by 70% and after 24 h had significantly (P less than 0.01) reduced the number of non-atretic follicles (greater than or equal to 1 mm diam.) without influencing the total number of follicles (greater than 1 mm diam.) compared to untreated controls. Hourly injections of FSH (10 micrograms i.v. NIH-FSH-S12) for 24 h did not influence the number of non-atretic follicles but did negate the inhibitory effects of bFF on follicular viability. Hourly injections of FSH (50 micrograms i.v., NIH-FSH-S12) + bFF treatment for 24 h significantly increased the total number of non-atretic follicles, and particularly the number of medium to large non-atretic follicles (greater than 3 mm diam.) compared to the untreated controls (both P less than 0.01). The 10 micrograms FSH regimen (without bFF) significantly increased aromatase activity in granulosa cells from large (greater than or equal to 5 mm diam.; P less than 0.01) but not medium (3-4.5 mm diam.) or small (1-2.5 mm diam.) follicles compared to controls. The 10 micrograms FSH + bFF regimen had no effect on granulosa-cell aromatase activity compared to the controls. However, the 50 micrograms FSH plus bFF regimen increased the aromatase activity of granulosa cells from large, medium and small non-atretic follicles 2.6-, 8.3- and greater than or equal to 11-fold respectively compared to that in the control cells. Ewes (N = 11) that ovulated 2 follicles had significantly higher plasma FSH concentrations from 48 to 24 h and 24 to 0 h before the onset of a cloprostenol-induced follicular phase (both P less than 0.01) than in the ewes (N = 12) that subsequently ovulated one follicle. Hourly FSH treatment (1.6 micrograms i.v., NIAMDD-FSH-S15) for 24 h but not for any 6 h intervals between 48 and 24 h or 24 and 0 h before a cloprostenol-induced luteolysis also resulted in significant increases (P less than 0.05) in the number of ewes with 2 ovulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Effects of long-term treatment with LH on induction of cyclic ovarian activity in seasonally anoestrous ewes.

The aim of the present study was to establish whether cyclic ovarian activity could be induced and then maintained in anoestrous Romney ewes by the long-term administration of regular intravenous pulses of LH (10 micrograms ovine LH i.v. once every 1 or 2 h for 29-91 days). The LH pulse regimen was designed to generate plasma profiles of LH that were comparable to those experienced during the luteal and follicular phases of the oestrous cycle. The results showed that the LH treatments were capable of inducing cyclic ovarian activity, as assessed from the concentrations of progesterone in plasma, but that the treatments were inadequate for sustaining cyclic activity beyond two consecutive progestational phases. After 35-56 days of treatment, the plasma concentrations of FSH declined significantly (P less than 0.05) relative to those in the untreated animals. These data suggest that FSH supplementation as well as LH might be required for the long-term maintenance of cyclic ovarian activity in seasonally anoestrous ewes.

Animals↗
PubMed1984

Seasonal differences in ovarian activity in cows.

The plasma concentrations of LH and prolactin and various parameters of ovarian function were examined in cows on known days of the oestrous cycle during May and June (autumn and winter) and during October (spring). Luteinizing hormone peak frequency and plasma prolactin concentrations were significantly higher in October than during the May-June period (LH, P less than 0.05; prolactin, P less than 0.01). The mean diameters of large healthy follicles (greater than or equal to 8 mm diameter) and the dominant oestrogen-secreting follicles were significantly larger (P less than 0.01 for both follicle types) and each follicle contained more granulosa cells (both P less than 0.01) in May-June than in October. The LH responsiveness of theca interna with respect to androstenedione production and the levels of aromatase activity in granulosa cells did not differ with time of year. The corpora lutea were heavier (P less than 0.05) and secreted more progesterone (P less than 0.01) in May-June than in October. It is concluded that seasonal differences in ovarian activity exist in cows and that these differences are probably the consequence of seasonal differences in gonadotrophin secretion.

Androstenedione↗
PubMed1984

Increase in ovulation rate after active immunization of sheep with inhibin partially purified from bovine follicular fluid.

Four Romney ewes were actively immunized with a partially purified preparation of inhibin derived from bovine follicular fluid and their ovulation rates in four successive oestrous cycles were compared with those of four ewes receiving adjuvant alone. The ovulation rates of the ewes immunized with the inhibin preparation were significantly higher than those of the control ewes (2.06 +/- 0.16 (S.E.M.) vs 1.31 +/- 0.06 ovulations/ewe, n = 4). Plasma concentrations of FSH and LH, measured in blood samples taken three times a week for 11 weeks, during which time each ewe was immunized three times, were not significantly different between the two treatment groups. These results suggest that active immunization with inhibin-enriched follicular fluid may be a potential means of increasing fecundity in sheep.

Animals↗
PubMed1983

Sphingomyelinase in cultured skin fibroblasts from normal and Niemann-Pick type C patients.

The sphingomyelinase activities of extracts of normal cultured skin fibroblasts were compared with those obtained from Niemann-Pick disease Type A and B patients, and from a number of patients with a provisional clinical diagnosis of Niemann-Pick disease Type C. Even though fibroblasts from Type A and B patients were shown to be clearly deficient (less than 5% residual activity) the activity in Type C fibroblasts varied from approximately 50% of the lowest control value to normal activity. Isoelectric focussing of extracts of normal cultured skin fibroblasts on polyacrylamide gels revealed the presence of sphingomyelinase heterogeneity. However, no characteristic change in the behaviour of the enzyme in corresponding extracts from Niemann-Pick Type C cells was observed, suggesting that, if the defect in this condition is expressed fibroblasts, it does not manifest biochemically in the appearance or disappearance of a specific sphingomyelinase isoenzyme. Our data suggest that the heterogeneity observed in fibroblast extracts may simply reflect an interaction of the enzyme either with itself or with other hydrophobic components present in the cellular extracts.

Cell Line↗
PubMed1982

Induction of cyclic ovarian activity in seasonally anoestrous ewes with exogenous GnRH.

Anoestrous ewes (N = 3) were treated with a 500 ng GnRH pulse administered via a jugular cannula every 2 h for 40 to 80 days. Plasma concentrations and therefore presumed ovarian activity changed cyclically with each progestational cycle (n = 10) lasting 14.0--18.5 days. It is concluded that, by increasing the frequency of GnRH secretory episodes from an apparent endogenous level of one episode per 3.6 h to at least one every 2.0 h, cyclic ovarian activity can be restored to seasonally anoestrous sheep.

Anestrus↗