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Biomedical subjects

M F Smith

Publications and source records attributed to M F Smith.

At least 199 records · Page 11Linked to original sources

A rapid and quantitative method for the determination of interleukin-1 alpha and -beta mRNA expression in human monocytes and macrophages.

We have used IL-1 alpha and IL-1 beta specific RNA standards in an RNA dot blot assay to rapidly and quantitatively assess the differential expression of the two human interleukin-1 mRNAs. This approach enabled us to minimize inaccuracies due to differences in specific activities of the probes, transcript size, and transfer and/or hybridization efficiencies of the two transcripts. We were thus able to accurately determine the steady state levels and molar ratio of the two species of IL-1 mRNA in human peripheral blood monocytes (PBM) and alveolar macrophages (AM). PBM, upon stimulation by lipopolysaccharide (LPS), expressed approximately ten-fold more IL-1 beta mRNA than IL-1 alpha. AM, however, expressed only two-fold more IL-1 beta then IL-1 alpha. PBM aged in vitro for 7 days prior to LPS stimulation, expressed at least 20-fold more IL-1 beta than IL-1 alpha RNA and at levels significantly lower than either PBM or AM.

Blotting, Northern↗

Ovarian inhibition of peripheral plasma concentration of follicle stimulating hormone in prepuberal Holstein heifers.

The objective of this study was to determine effects of age and castration on follicle stimulating hormone (FSH) secretion in prepuberal heifers. In experiment 1, twelve heifers were bilaterally ovariectomized at 3, 6, or 9 months of age (n = 4/group). Blood was collected at 10 min intervals for 8 hr at 1 week before ovariectomy and 1 and 4 weeks after ovariectomy. Frequency, amplitude and duration of FSH pulses were calculated. Mean plasma concentration of FSH (ng/ml), and frequency (pulses/8 hr), amplitude (ng/ml), and duration (min/pulse) of FSH pulses were not altered by age. Mean concentration of FSH increased (P less than .01) from 1 week before to 1 week and 4 weeks after ovariectomy, respectively, in all age groups. Pulse frequency increased (P less than .05) from 1 week before ovariectomy to 4 weeks after ovariectomy in 3 month old heifers, from 1 week before to 4 weeks after ovariectomy in 6 month old heifers, and from 1 week before to 1 week and 4 weeks after ovariectomy in 9 month old heifers. In experiment 2, twelve heifers were bilaterally ovariectomized at 3, 6 or 9 weeks of age (n = 4/group). Sample collection and measurement of mean concentration of FSH were the same as in experiment 1. Mean concentration of FSH increased (P less than .01) from 1 week before to 1 and 4 weeks after ovariectomy in heifers ovariectomized at 6 and 9 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Oxytocin-induced release of prostaglandin F2 alpha in postpartum beef cows: comparison of short versus normal luteal phases.

The first postpartum ovulation after early weaning of calves (30 35 days of age) from cows is normally followed by a short luteal phase (6 10 days) unless the animals are pretreated with a progestogen (e.g. norgestomet). Reduced luteal lifespan in cattle is reportedly due to the premature release of a luteolysin (presumably prostaglandin F2 alpha [PGF2 alpha]). Therefore, the objective was to determine if oxytocin-induced release of PGF2 alpha (measured by the stable PGF2 alpha metabolite, 15-keto-13,14-dihydro PGF2 alpha [PGFM]) was greater for cows having a short compared to a normal luteal phase on Day 5 following the first postpartum estrus (Day 0). Thirty postpartum beef cows were randomly assigned into three groups (n = 10 per group) expected to have short (Short d 5) or normal (Norgestomet d 5 and Norgestomet d 16) luteal phases. Cows in Norgestomet d 5 and d 16 groups received Norgestomet (progestogen) implants for 9 days beginning 21 23 days postpartum. On Day 5 (Short d 5 and Norgestomet d 5) or Day 16 (Norgestomet d 16) following first postpartum estrus, each animal was injected (i.v.) with 100 IU oxytocin. In addition, cows in the Short d 5 group were subdivided into two groups following second estrus (normal luteal phase, n = 5 per group) to receive 100 IU oxytocin on Day 5 (Normal d 5) or 16 (Normal d 16), respectively. Estrous cycle length (means +/- SE) for cows in the Short d 5 group (8.7 +/- 0.4 days) was shorter (p less than 0.01) than for cows in all other groups (21.1 +/- 0.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Click evoked otoacoustic emissions compared with brain stem electric response.

The hearing of 346 babies taken largely from a neonatal intensive care unit has been tested by otoacoustic emissions and brain stem electric response audiometry. A total of 336 (97%) of the babies have been followed up by hearing tests from the age of 8 months. The otoacoustic emission test has been found to be practical with a mean test time of 12.1 minutes compared with 21.0 minutes for brain stem electric response. An otoacoustic emission was recorded bilaterally in 274 (79%) babies. Twenty of the 21 surviving infants who failed brain stem electric response in the neonatal period did not produce an emission. It is concluded that the otoacoustic emission test would make a good first screen to be followed by the brain stem electric response if no otoacoustic emission was present. There is poor agreement between the test results in the neonatal period and those of the follow up period, however, indicating the need for continuous monitoring of those babies failed by brain stem electric response.

Acoustic Stimulation↗

Effect of active immunization of pre-partum and post-partum cows against prostaglandin F-2 alpha on lifespan and progesterone secretion of short-lived corpora lutea.

Mature beef cows were actively immunized pre partum (N = 5) or post partum (N = 10) against a PGF-2 alpha-ovalbumin conjugate or against ovalbumin alone (control; N = 5). All cows in the control group exhibited first oestrous cycles which were of short duration (less than or equal to 12 days). Mean specific serum binding to [3H]PGF-2 alpha in the control group was consistently less than 1%. In the pre-partum PGF-2 alpha-immunized cows, lifespan and progesterone secretion of the first corpus luteum formed post partum was maintained for greater than 39 days. Specific serum binding to [3H]PGF-2 alpha in pre-partum and post-partum PGF-2 alpha-immunized cows was elevated. Lifespan of the first corpus luteum formed in post-partum PGF-2 alpha-immunized cows was short (less than 10 days; N = 1), normal (mean = 22 days; N = 4) or maintained (greater than 31 days; N = 5). Luteal lifespan was dependent upon serum PGF-2 alpha antibody titres, with cows exhibiting higher titres frequently having prolonged luteal lifespans after first ovulation. We conclude that active immunization of beef cows against PGF-2 alpha extends the lifespan and progesterone secretion of corpora lutea anticipated to be short-lived. These results support the concept that the shorter lifespan of some corpora lutea in post-partum cows is due to a premature release of PGF-2 alpha from the uterus.

Animals↗

Effect of termination of pregnancy or long-term progestogen exposure on subsequent estrous cycle length and concentration of progesterone in plasma of heifers.

An experiment was conducted to determine whether short estrous cycles following abortion of heifers between 70 and 75 d of gestation are due to factors associated with the previous presence of a conceptus or long-term exposure of the uterus and(or) ovaries to a progestogen. Fifty crossbred heifers were randomly allotted at estrus (d 0) to five groups: control (n = 10), pregnant (Preg.; n = 14), progestogen (norgestomet) implant (Norg.; n = 9), progesterone-releasing intravaginal device (PRID; n = 9), or hysterectomy (Hyst.; n = 8). Control heifers were injected during the mid-luteal phase of an estrous cycle with 25 mg prostaglandin F2 alpha (PGF2 alpha) and length of the subsequent estrous cycle was determined. Beginning 6 to 8 d after estrus, heifers in the Norg. or PRID groups were given norgestomet ear implants or intravaginal coils, respectively, every 10 d for 70 d. Heifers were hysterectomized 5 to 8 d after estrus. Seventy to 75 d after conception, progestogen treatment or hysterectomy, heifers were injected (i.m.) with 25 mg PGF2 alpha and the last norgestomet ear implants or PRIDs were removed. Interval from PGF2 alpha injection to first estrus (means +/- SE) ranged from 2.5 +/- .2 to 4.4 +/- .7 d (P greater than .05). Length of the first estrous cycle means +/- SE) following PGF2 alpha-induced luteolysis or progestogen withdrawal was shorter (P less than .01) for the Preg. group (8.2 +/- .4 d) than for the control, Norg. and PRID groups (21.5 +/- .6 d; 19.3 +/- 1.4 d; and 18.2 +/- 1.3 d, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗

Effect of bovine follicular fluid and follicle-stimulating hormone on follicular growth in unilaterally ovariectomized prepuberal heifers.

A study was conducted to determine if charcoal-extracted follicular fluid inhibits FSH-induced follicular development in prepuberal heifers. Thirty-six prepuberal heifers were allotted by breed and weight to a 2 x 2 factorial experiment involving charcoal-extracted follicular fluid and FSH treatments. Heifers were unilaterally ovariectomized and injected (intravenously; 10 ml) every 8 h for 88 h with either charcoal-extracted follicular fluid or saline. Follicle-stimulating hormone (2 mg) or saline was injected (intramuscularly) every 8-h starting 24 h after initiation of charcoal-extracted follicular fluid to 88 h following unilateral ovariectomy. Plasma samples were collected at 8-h intervals from 48 h prior to unilateral ovariectomy to 96 h following unilateral ovariectomy when the remaining ovary was removed. Follicular fluid and total ovarian weight increased following FSH treatment. The increases were not inhibited by charcoal-extracted follicular fluid. Total number of surface follicles was similar among treatments. However, FSH induced a shift in follicular diameter from small (less than or equal to 3 mm) to medium (7 to 9 mm) or large (10 to 13 mm) follicles, which was unaffected by charcoal-extracted follicular fluid. Plasma concentration of FSH, but not LH, declined following charcoal-extracted follicular fluid administration. In summary, charcoal-extracted follicular fluid did not inhibit FSH-induced follicular development in prepuberal heifers when charcoal-extracted follicular fluid was administered at a dosage that reduced circulating concentration of FSH by approximately 40%.

Animals↗

Genetic analysis of colorectal cancer.

Adenomatous polyposis, mainly of the colon, (APC) is a rare dominantly inherited susceptibility to colon cancer in which individuals develop hundreds of polyps mainly in their large bowel. The APC gene has been localised to chromosome 5q21 by following up a case report of an individual with an interstitial deletion on chromosome 5q who had multiple developmental abnormalities together with adenomatous polyposis. A DNA marker (D5S71) was found to be closely linked to APC in family studies and localised to 5q21 by in situ annealing. Material from further patients with deletions in this region of chromosome 5 has been used, by a combination of somatic cell hybrid and long-range DNA analysis, to identify new DNA markers close to the APC gene. These and other markers now provide the basis for genetic counselling of nearly all families with APC. These studies are being extended, together with other approaches for analysing DNA clones around the APC gene, in the search for the gene itself. Allele loss in tumour as compared to normal tissue from sporadic cases of colorectal carcinomas has clearly implicated the APC gene in at least 25 to 40% of all cases of colorectal carcinomas. Similar studies by Vogelstein and others as well as ourselves have further implicated recessive changes on chromosomes 17 and 18 in the development of colorectal carcinomas. Following the demonstration by Vogelstein of the role of p53 mutations in connection with the chromosome 17 changes, we have now shown, using monoclonal antibodies to the mutant p53 products and by other approaches, that changes in the p53 gene may occur in up to 50% or more of colorectal carcinomas. Frequent mutations of the K-ras dominant oncogene, as well as changes in the expression of human leucocyte antigen (HLA)-A, B, C determinants, are further genetic changes that appear commonly to be involved in the progression of colorectal carcinomas. The latter have important implications for T cell immune response to tumours and its manipulation for treatment and even prevention of colorectal cancer. We may soon be approaching a situation when it will become possible to identify all the genetic steps and their sequence during tumour progression, as well as their functional significance largely through the induction of inappropriate growth and the suppression of differentiation.

Adenomatous Polyposis Coli↗

Stressors and psychological symptoms of family practice residents and spouses.

Fifty-nine family practice residents and their spouses from one university-based and three community-based residency programs were studied to assess the frequency of stressful events in their lives and to quantify adverse psychosocial effects associated with that stress. A modified version of a questionnaire produced and tested by the University of Minnesota and the widely used, standardized Symptom Checklist-90 (SCL-90) were used to assess stress and psychological symptoms. There was a high correlation between high numbers of stressful events in the residents' and spouses' lives and high ratings of psychological symptoms. This finding was particularly true for the female residents. Overall, the residents' responses were near the mean for a nonpatient group used as a normative comparison on each of the nine subscales of the SCL-90 and on the overall mean for the entire scale. This finding indicated that the residents, although their lives were quite stressful, were handling the stress without major problems. The residents and their spouses also answered questions about 10 therapeutic interventions concerning stress and indicated which interventions they preferred.

Family Practice↗

Ketoconazole as primary treatment of prostatic cancer.

Ketoconazole 400 mg 8-hourly was used as primary hormonal treatment in 12 patients with advanced prostatic carcinoma. Four patients were withdrawn because of side effects and 1 died. The 7 patients who tolerated the drug had a reduction in testosterone and adrenal androgens. Six patients were fully evaluable. There was one partial response with complete remission of symptoms. Two patients enjoyed a subjective response and 3 showed no response. Ketoconazole had an effective biochemical action but the side effects seen in this study severely limit its usefulness. Ketoconazole has now been withdrawn as a treatment for prostatic cancer. However, less toxic derivatives might prove a useful addition to the drugs available to treat this condition.

Adrenal Cortex Hormones↗

Cerebral systemic lupus erythematosus.

Cerebral systemic lupus erythematosus is uncommon in childhood. Three further cases are presented to draw attention to the unusual and varied clinical manifestations of this condition.

Brain Diseases↗

Relationship of pre- and post-ovulatory gonadotropin concentrations to subnormal luteal function in postpartum beef cattle.

Early weaning of calves from anestrous cows results in formation of short-lived corpora lutea (CL) unless the animals are pretreated with a progestagen (norgestomet). This study was conducted to investigate the relationship between pre- and post-ovulatory gonadotropin secretion and luteal lifespan. Postpartum beef cows were assigned randomly into two groups, control (n = 5) and norgestomet (implant given at weaning for 9 d; n = 7). Calves from all cows were weaned 30 to 33 d postpartum. Coccygeal artery cannulas were placed into cows in the control group 1 d prior to weaning and 2 d before implant removal in cows in the norgestomet group. Plasma for determination of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol-17 beta (E) and progesterone (P) was collected daily at 10-min intervals for 6 h from weaning (control) or the day prior to implant removal (norgestomet) to estrus (d 0) and on d 2, 4 and 6 following estrus. Average interval (X +/- SE; P less than .05) from weaning to estrus or implant removal was 4.2 +/- .8 and 2.3 +/- .2 d for the control and norgestomet groups, respectively. Estrous cycle length for the control group was 12.4 +/- 1.8 d compared with 20.4 +/- .3 d for the norgestomet group (P less than .05). Four of five control cows had an estrous cycle length of 7 to 14 d; all cows in the norgestomet group and the remaining control cow had an estrous cycle of normal length (16 to 21 d).2+ estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Responsiveness of bovine corpora lutea to prostaglandin F2 alpha: comparison of corpora lutea anticipated to have short or normal lifespans.

The objective of this study was to determine if corpora lutea anticipated to have short lifespans were more responsive to the luteolytic action of prostaglandin F2 alpha (PGF2 alpha) than corpora lutea anticipated to have normal lifespans. Sixteen cows were allotted randomly to a hysterectomized-control (HC) or hysterectomized-progestogen (norgestomet) implant (HN) group. To verify that progestogen treatment of postpartum cows prior to induction of ovulation with gonadotropin-releasing hormone (GnRH) results in an increased number of cows exhibiting normal-length luteal phases, 21 additional cows were allotted randomly to a uterine intact-control (IC) or a uterine intact-progestogen implant (IN) group. Cows allotted to the HN and IN groups received norgestomet ear implants for 9 d beginning 17 to 21 d postcalving. All cows were injected (i.m.) with 100 micrograms GnRH 28 to 32 d postcalving (48 h after implant removal in the HN and IN groups) to induce ovulation. Two or 3 d after GnRH injection (d 0), cows in the HC (n = 8) and HN (n = 8) groups were hysterectomized to remove the major endogenous source of PGF2 alpha, and on d 7 cows were injected (i.m.) with 10 mg PGF2 alpha to assess luteal sensitivity. The proportion of corpora lutea having normal lifespans was greater (P less than .1) for the IN than for the IC group. In HC and HN groups, concentration of progesterone (P) increased similarly from d 0 to 6. Injection of PGF2 alpha in HC and HN groups on d 7 decreased (P less than .01) concentration of P approximately 50% by 6 h after injection (similar for both groups). Complete luteolysis was induced by PGF2 alpha in none of eight and two of eight cows in the HC and HN groups, respectively. In remaining cows (HC and HN groups) concentration of P increased (P less than .01; similar for HC and HN groups) beginning 24 h after PGF2 alpha and remained elevated through d 30 to 34 (end of experimental-period). In summary, corpora lutea anticipated to be short-lived were not more responsive to PGF2 alpha than corpora lutea anticipated to have normal lifespans.

Animals↗

The surviving child in the SIDS family.

Children grieve, often very deeply. The unexpected loss of an infant elicits grieving from all family members and alters forever the family structure. What is the long-term impact of the death of a child in the family on the surviving sibling? What happens to children surviving this family catastrophe when they themselves become parents? In this report we present two accounts by children in the home when their siblings died. It reminds us that the effects of a sudden and unexpected loss of a child in the family can be long-lasting and return to us in childrearing practices of the next generation.

Adaptation, Psychological↗

A randomized study of 5-fluorouracil and filtration surgery.

We conducted a randomized study of 26 patients with a poor prognosis undergoing filtration surgery with and without a low dose of 5-fluorouracil. Mean preoperative intraocular pressure (+/- S.E.M.) in the 5-fluorouracil group (n = 14) was 38.4 +/- 3.08 mm Hg; in the control group (n = 12) it was 41.2 +/- 5.0 mm Hg. Mean postoperative intraocular pressure (+/- S.E.M.) at six to 18 months was 14.4 +/- 1.4 mm Hg in the 5-fluorouracil group and 30.7 +/- 3.9 mm Hg in the control group (P less than .01). Of 14 patients in the 5-fluorouracil group, 12 had a successful outcome at 12 months. Of 12 patients in the control group, three had a successful outcome during this same interval.

Female↗

Induction of interleukin 2 receptor (TAC) by tumor necrosis factor in YT cells.

The effect of human recombinant tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) on interleukin 2 receptor (IL-2R) expression on YT cells was examined. IL-2R expression was assessed by flow cytometric analysis with a monoclonal antibody to IL-2R (anti-TAC). TNF-alpha, like IL-1 beta, induced increased levels of IL-2R expression on YT cells with similar kinetics of induction. Maximum induction occurred at 20 to 30 hr. On a molar basis. TNF was less active than IL-1 beta. RNA isolated from TNF-alpha- or IL-1 beta-treated YT cells contained increased levels of IL-2R-specific mRNA as indicated by slot blot analysis by using an IL-2R-specific mRNA probe. Kinetic and IL-1 beta mRNA expression studies indicated that the TNF effect was a direct one. Because IL-2R expression is known to be associated with lymphocyte activation, the present results suggest that TNF-alpha may play a role in the regulation of immune responses.

Cell Line↗