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Biomedical subjects

K Gordon

Publications and source records attributed to K Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1995

Predictors of sunscreen use in childhood.

OBJECTIVE: To identify risk factors predictive of sunscreen use in children. DESIGN: Cross-sectional review of convenience sample. SETTING: Emergency department of a regional referral pediatric hospital. SUBJECTS: Nine hundred twenty-five parents of children presenting to the emergency department in August 1993. MAIN OUTCOME MEASURES: Parental risk factors assessed were use of sunscreen, tanning behaviors, previous blistering sunburn, knowledge of cancer risk related to sunburn and sun protection factor definition, education level, and other health-promoting behaviors. The parents were asked about perceived risk for their child's being sunburned in the next month or development of skin cancer in their lifetime, as well as an estimation of safe sun exposure time for their child. Child risk factors included a history of previous painful sunburn and parental assessment of their child's skin type based on susceptibility to sunburn. RESULTS: Eighty-four percent of parents reported that their children had used sunscreen at least once in the previous 2 months. The use of sunscreen in children younger than 1 year was 54%, from 1 to 12 years of age was 91%, and older than 12 years was 68%. Factors associated with increased likelihood of sunscreen use were age of 1 to 12 years, parental use of sunscreen, estimation of safe sun exposure of less than 30 minutes, description of child skin type as burns "sometimes," "easily," or "always," and correct definition of sun protection factor. Application of a multivariate model yielded a sensitivity of 96%, specificity of 36%, and positive predictive value of sunscreen use of 89%. CONCLUSIONS: Sunscreen use in parents is predictive of use in their children and relates more to experience with sunburn than with concerns about future skin cancer risk.

Adolescent↗
PubMed1995

Clinical correlates of subnormal vitamin B12 levels in patients infected with the human immunodeficiency virus.

OBJECTIVES: To determine the prevalence and describe the clinical correlates of subnormal cobalamin levels in subjects infected with the human immunodeficiency virus (HIV), and to assess its relationship to virus-mediated immunosuppression and/or anti-viral therapy. SETTING: Outpatient referral clinic in tertiary care hospital. PATIENT POPULATION: 200 HIV infected individuals. STUDY DESIGN: Descriptive cross sectional survey, with prospective follow-up in a subgroup of patients before and after initiation of zidovudine therapy. MEASURES: Routine complete blood count, serum B12 assay, CD4 counts. Serum homocysteine levels, and Schilling tests were performed on subgroups of study subjects. RESULTS: Subnormal serum B12 levels were found in 61 subjects (30.5%). B12 deficient subjects were more likely to be taking zidovudine. (P = .007). Serum homocysteine levels were significantly higher in patients with subnormal cobalamin levels but were unrelated to CD4 counts or zidovudine use, and were rarely outside of the normal range. Malabsorption of vitamin B12 as evidenced by abnormal Schilling tests was more likely among patients with more advanced HIV disease, or gastrointestinal symptoms but was not necessarily associated with low B12 levels. CONCLUSIONS: Decreased cobalamin levels are found frequently in HIV disease, especially among those treated with zidovudine. Evidence of B12 malabsorption is found among those with more advanced disease and gastrointestinal symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Primate reproductive organs reveal a novel pattern of proto-oncogene c-mos and transcription factor Oct-3 mRNA expression.

In mice, expression of the transcription factor Oct-3 and the proto-oncogene c-mos is limited to germ cells, suggesting a specific role for these factors in gamete physiology and early embryonic development. We have studied the expression pattern of Oct-3 and c-mos in various reproductive as well as control tissues in the cynomolgus monkey, using reverse transcriptase polymerase chain reaction (RT-PCR) and Northern analysis. Analogously with the data from the mouse model, strong expression of Oct-3 and c-mos could be detected in monkey ovary and oocytes. Unexpectedly, strong expression of c-mos was demonstrable in the pituitary gland and the amount of mRNA expression in the pituitary was roughly equal to that found in the ovary. Of the tissues examined, the testicular expression of c-mos was the most intense. Weak signal for c-mos mRNA was also seen in hypothalamus and brain; however, all other tissue types examined were negative for c-mos expression. In addition to the oocytes, expression of Oct-3 mRNA was detected in the ovarian granulosa cells, fallopian tube, myometrium, cervix, breast, liver, adrenal gland, pituitary, hypothalamus, brain cortex, prostate, and in testis. Thus, in the cynomolgus monkey, Oct-3 is predominantly, but not specifically, expressed in reproductive tissues. In the female monkey reproductive organs, the expression of c-mos seems to be germ cell specific. Therefore, further characterization of c-mos and Oct-3 functions in primate reproductive physiology, especially in gametogenesis and early embryonic development, is highly warranted.

Animals↗
PubMed1995

Estrogen and progesterone receptor mRNA are expressed in distinct pattern in male primate reproductive organs.

PURPOSE: The role(s) of estrogens (E) and progesterone (P) in male reproductive physiology remain unclear. Estrogens are used in the treatment of prostatic cancer. Progestins have been used to control excessive sexual behavior in men, and proposed as a male contraceptive. Previous immunohistochemical studies have shown that E receptors (ER) are present in the reproductive tract of male nonhuman primates. METHOD: We examined the expression pattern of ER and progesterone receptor (PR) mRNA in adult primate male reproductive tract. mRNA was extracted from male pituitary, testis, prostate and different regions of the epididymis of three intact adult cynomolgous monkeys. Ovarian, myometrial and spleen mRNA were used as controls. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify ER and PR mRNA; beta-actin mRNA was used as a reference. Primers for ER, PR and beta-actin were designed using the most conserved areas in the corresponding human cDNA sequences, and the identity of the PCR products was verified using Southern hybridization. Semiquantitative analysis of ER and PR mRNA content in different parts of the male reproductive tract was carried out by spiking the PCR reaction with 33P-dCTP, and amplifying the samples for 20 cycles with the beta-actin primers, whereas 30 cycles were used for ER and PR. RESULTS: The results are expressed as cpm ratios of ER or PR/beta-actin. All the male reproductive organs studied revealed a strong signal for ER and PR mRNA. The results of the semiquantitative analysis indicate that the expression of both ER and PR was highest in testis (mean +/- SE 6.4 +/- 1.3 and 0.5 +/- 0.1, respectively). The mean figures for prostate were 0.5 and 0.4, respectively. The mean content of ER and PR in the different areas of epididymis was 0.5 and 0.1, respectively. The epididymal ER mRNA was highest in the corpus region (ER/beta-actin 0.7), the ratio being 0.4 for the caput and cauda regions. The expression pattern of PR mRNA was different, and the caput of epididymis being the most intense (0.2). Surprisingly, the pituitary content of ER and PR mRNA was close to that seen in the ovary, the mean +/- SE values being 7.6 +/- 0.5 and 1.3 +/- 0.1, respectively. CONCLUSIONS: We, therefore, conclude that male monkey reproductive tract contains mRNA for ER and PR, and there appears to be regional variation in their expression. Thus the role(s) of Es and P in male reproductive physiology, specifically in sperm maturation, warrants further investigations.

Actins↗
PubMed1995

Lactational anovulation in non-human primates: restriction of nursing inhibits Prl secretion without precipitating the return of ovulatory menstrual cyclicity in cynomolgus monkeys.

To test the hypotheses that nighttime suckling and elevated nocturnal prolactin concentrations are essential for the continuation of lactational anovulation, the effects of restricting nursing to twelve h per day (either day or night) on maternal prolactin (Prl) levels and resumption of ovulatory menstrual cycles were studied in five groups of cynomolgus monkeys: Group 1: baby weaned: Group 2: baby fully nursed: Group 3: baby nursed night only; Group 4: baby nursed day only; and Group 5: baby housed with mother but not allowed to nurse. Restrictions were initiated at approximately 150 days postpartum and were achieved by placing a non-nursing jacket over the nursing jacket, which was worn 24 h/day. Fifteen out of seventeen monkeys remained anovulatory while housed with their infants, irrespective of the type of nursing restriction. First postpartum ovulations occurred approximately two months post-weaning. Plasma prolactin concentrations during both day and nighttime were significantly (p < 0.05) greater in the fully nursing group(s) than in all other groups. Fully nursing mothers had significantly (p < 0.01) greater prolactin concentrations at night than during the day. Among the restricted groups, the night only suckling group had significantly greater prolactin concentrations at night than the other restricted groups. There were no differences between daytime values, and within each restricted group there were no significant differences between day and night prolactin levels. We conclude that 1) nighttime suckling is not an absolute prerequisite for sustained lactational anovulation, and 2) suckling-induced hyperprolactinemia is not the principle mediator of lactational anovulation.

Animals↗
PubMed1995

Ruthenium Red potently inhibits immune responses both in vitro and in vivo.

Targeted drug screening revealed a compound, Ruthenium Red, which potently blocked proliferation of human T-cells. This compound is not generally cytotoxic or cytostatic, as judged by its lack of effect on the proliferation of a panel of transformed cell lines, but it exhibits true immunosuppressive properties. Ruthenium Red inhibits the T-cell proliferative response (with an IC50 approximately 100 nM) to a wide variety of agents, including viral antigens from herpes simplex virus, tetanus toxoid, alloantigens and IL-2. This compound did not alter the growth of an M-CSF-dependent cell line (M-NFS-60) in response to added growth factor. Time course studies revealed that Ruthenium Red could be added as late as 24 h after the initiation of T-cell stimulation by antigen and still produce maximal inhibition, indicating that later stages of signaling events are being effected. Ruthenium REd was then tested for its ability to abrogate immune response in vivo. It was discovered that this compound dramatically reduced the expansion of lymphocytes in draining lymph nodes of mice immunized with cytochrome c in adjuvants. Furthermore, Ruthenium Red also suppressed specific antibody production in mice following challenge with this antigen. The functional properties of Ruthenium Red have been compared with other immunosuppressive agents and reveal that this compound is most similar to rapamycin in its overall profile. The chemical structure of Ruthenium Red is quite different from these other agents; therefore, it may be extremely useful in helping dissect the activation pathway of T-cells. It will be important to explore further the therapeutic potential of this unique compound.

Animals↗
PubMed1995

Reduced neonatal liver iron concentrations after uteroplacental insufficiency.

Neonatal liver (storage) but not heart (nonstorage) tissue iron concentrations were reduced by 60% at autopsy in 15 newborn infants who had gestations complicated by uteroplacental insufficiency because of maternal hypertension or Potter syndrome. The hepatic iron reductions in term and preterm infants, and with either antecedent condition, were similar.

Case-Control Studies↗
PubMed1995

EEG results are rarely the same if repeated within six months in childhood epilepsy.

OBJECTIVE: To assess the reliability of interictal spike discharge in routine electroencephalography (EEG) testing in children. METHOD: EEG results of all children diagnosed in Nova Scotia with epilepsy onset between 1977-85 (excluding myoclonic, akinetic-atonic and absence) were reviewed. The results of the EEG at time of diagnosis (EEG1) were compared with those of a second EEG (EEG2) within 6 months. RESULTS: Of 504 children with epilepsy, 159 had both EEG1 and EEG2. EEG2 was more likely ordered if EEG1 was normal or showed focal slowing but less likely if EEG1 contained sleep (p < 0.05). EEG1 and EEG2 were both normal in 23%. If EEG1 was abnormal, there was a 40-70% discordance for the type of abnormality on EEG2. Abnormalities were present on both EEG1 and EEG2 in 67 cases. Of the 42/67 with major focal abnormalities on EEG1, 7 had only generalized spike wave on EEG2. Of the 17/67 with only generalized spike wave on EEG1, 7 showed only major focal abnormalities on EEG2. Statistical testing showed low Kappa scores indicating low reliability. CONCLUSIONS: The interictal EEG in childhood epilepsy appears to be an unstable test. A repeat EEG within 6 months of a first EEG may yield different and sometimes conflicting information.

Child↗
PubMed1995

Cellular events in the evolution of experimental diabetic nephropathy.

In several models of progressive glomerular disease, mesangial cell proliferation, phenotypic change and increased growth factor expression precede up-regulation of genes for extracellular matrix components (ECM) and mesangial expansion. To examine these events in diabetic nephropathy (DN) we conducted sequential studies of glomeruli in rats with streptozotocin induced DN. We found prominent mesangial cell proliferation at three days (4.34 +/- 2.24 PCNA + cells/glom vs. 1.6 +/- 0.74 in controls, P < 0.001) associated with increased alpha-actin expression. PDGF B-chain mRNA was slightly increased at day one, and PDGF B-chain immunostaining was slightly increased at days one and six. Staining for bFGF was significantly increased at three days (2.2 +/- 0.6 vs. 1.2 +/- 0.1 in controls, P < 0.01). There was also an early increase in platelets in glomeruli of diabetic animals, and platelet depletion significantly inhibited the early phase of proliferation. In addition to mesangial cell proliferation, a prominent glomerular macrophage infiltration began at day three and peaked at day 30 (3.94 +/- 1.47 vs. 2.08 +/- 1.13 in controls, P < 0.01). TGF-beta mRNA increased at days 14 and 30. Insulin treatment prevented mesangial cell proliferation, actin expression, and macrophage infiltration, and normalized TGF-beta expression at 14 and 30 days. These multiple cellular events preceded any detectable increases in glomerular gene expression or deposition of collagen I, IV or laminin.

Animals↗
PubMed1995

Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo.

Thrombospondin 1 has been shown to be linked to PDGF-mediated mesangial cell proliferation and migration in vitro, but little is known regarding its expression or regulation in glomerular disease. Experimental mesangial proliferative nephritis was induced in rats by injection of anti-Thy1 antibody. Mesangial cell proliferation was associated with de novo expression of thrombospondin 1 mRNA (detected by Northern blot and in situ hybridization) and protein (by Western blot and immunostaining). Although some thrombospondin 1 was expressed by platelets and macrophages, double labeling showed that most thrombospondin 1 mRNA and protein were expressed by proliferating alpha-actin-positive mesangial cells. Thrombospondin 1 expression in anti-Thy1 nephritis was complement-dependent and could be reduced by treatment with anti-PDGF or anti-bFGF antibodies. Thrombospondin 1 could also be induced in normal rats by infusion of PDGF and in rats which were primed with low dose anti-Thy1 antibody by infusion of PDGF of bFGF. Thus, this study demonstrates that proliferating mesangial cells express thrombospondin 1 de novo in disease and that thrombospondin 1 expression in vivo is regulated by PDGF and bFGF.

Animals↗
PubMed1995

Modulation of experimental mesangial proliferative nephritis by interferon-gamma.

The observation that interferon-gamma (IFN-gamma) inhibits cell proliferation and collagen synthesis of a variety of cell types in culture has suggested that IFN-gamma may be useful in the treatment of fibroproliferative diseases. We administered recombinant IFN-gamma subcutaneously (10(5) U/kg/day for 3 days) to rats, beginning one day after the induction of mesangial proliferative nephritis with anti-Thy 1 antibody. IFN-gamma reduced glomerular (primarily mesangial) cell proliferation by 44% at days 2 and 4 compared to vehicle injected control rats with anti-Thy 1 nephritis (that is, proliferating cells that excluded the macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell proliferation, IFN-gamma did not reduce the overall extracellular matrix deposition (by silver stain) or deposition of type IV collagen or laminin (by immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The inability of IFN-gamma treatment to reduce mesangial matrix expansion may relate to the fact that IFN-gamma treated rats had a twofold increase in glomerular macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in glomerular TGF-beta mRNA expression (4 days). This suggests that the effect of IFN-gamma to inhibit mesangial cell proliferation in glomerulonephritis may be offset by the ability of IFN-gamma to increase glomerular macrophages and TGF-beta expression. These data also show that IFN-gamma can partly dissociate the mesangial proliferative response from the extracellular matrix expansion in glomerulonephritis.

Animals↗
PubMed1995

The role of endothelin-1 in regulating human granulosa cell proliferation and steroidogenesis in vitro.

The effects of endothelin-1 (ET-1) on luteinized human granulosa cells (L-HGCs) have not been examined. It is well known that there are differences of actions of several autocrine/paracrine regulators between L-HGCs and GCs of other species, and therefore the present study was designed to examine the effects of ET-1 1) on intracellular Ca2+ concentrations ([Ca2+]i) using the Ca(2+)-responsive fluorescent indicator Fura-2, 2) on cell proliferation by the nonradioactive method using bromodeoxyuridine, and 3) on basal and gonadotropin-stimulated steroidogenesis, and to examine the expression of ET receptor messenger RNA (mRNA) using freshly isolated and cultured L-HGCs obtained from patients undergoing in vitro fertilization. ET-1 increased [Ca2+]i in L-HGCs in a dose-dependent manner between 1 and 1000 nmol/L. High concentrations (100-1000 nmol/L) of ET-1 produced a more rapid and transient increase in [Ca2+]i than that observed with low concentrations (1-10 nmol/L) of ET-1. The increase in [Ca2+]i elicited by ET-3 (1000 nmol/L) and IRL-1620 (1000 nmol/L), a selective ETB receptor agonist, was 16% and 3% (vs. ET-1, 100%), respectively. BQ-123 (1000 nmol/L), an ETA receptor antagonist, inhibited the increase in [Ca2+]i elicited by ET-1 (by 50% at 1000 nmol/L ET-1 and by > 90% at < 500 nmol/L ET-1). mRNAs for the two known receptor subtypes (ETA and ETB) were also present in L-HGCs; however, the expression of ETA receptor mRNA was much greater than that of ETB receptors. ET-1 stimulated cell proliferation in L-HGCs in a dose-dependent manner (1000 nmol/L, 210.5 +/- 13.1%; 100 nmol/L, 198 +/- 11%; 10 nmol/L, 146 +/- 18%; and 1 nmol/L, 103 +/- 9%; vs. control, 100%). These stimulatory effects were completely blocked by BQ-123 (1000 nmol/L). ET-3 and IRL-1620 had no effects on cell proliferation in L-HGCs. Significant stimulatory effects on cell proliferation by the calcium ionophore, ionomycin (10-1000 nmol/L), were observed. ET-1, ET-3, and IRL-1620 attenuated basal progesterone secretion in L-HGCs. These results suggest that ETA receptor predominantly exist in L-HGCs and that ET-1 may stimulate cell proliferation of L-HGCs by increasing [Ca2+]i via ETA receptors.

Calcium↗
PubMed1995

Antiovulatory actions of RU 486: the pituitary is not the primary site of action in vivo.

Continuous administration of RU 486 impairs follicular development and inhibits ovulation in women. Yet, the mechanism of ovulation inhibition remains unknown. To characterize the mechanism(s) of ovulation inhibition, we studied six regularly menstruating cynomolgus monkeys for three consecutive (control-rest-treatment) cycles. Monkeys received 1 mg/kg.day RU 486 in between cycle days 2-22. Basal and GnRH-stimulated (1 and 50 micrograms GnRH, iv, 2 h apart) secretion of LH and FSH was assessed using serial blood samples (every 15 min for 12 h) collected on cycle day 10. Serum levels of estradiol (E2), progesterone (P4), RU 486, cortisol, LH, FSH, and PRL were analyzed by RIAs, the bioactivity of LH was assessed using a mouse Leydig cell assay. The mean cycle length was prolonged by RU 486 treatment from 31.8 to 69.8 days (P = 0.008). During RU 486 treatment, patterns of E2 secretion varied considerably; the mean +/- SD E2 level was 204 +/- 139 pmol/L. LH peaks and P4 profiles compatible with luteal function were seen only before resumption of menstruation. However, one monkey had an increase in P4 after the GnRH challenge-induced LH secretion. Basal levels of LH varied between suppressed and apparently normal values, whereas basal FSH seemed little affected by RU 486 treatment. In two monkeys with E2 secretion indicative of normal follicular development, minor peaks of LH, but no rises in serum P4, were seen. The ratio of bioactive/immunoactive LH was reduced in these monkeys during RU 486 treatment compared to that during the washout period of the treatment cycle. Surprisingly, the pituitary responsiveness to acute GnRH challenge was not affected by RU 486 administration. The individual levels of RU 486 were similar during the treatment period (mean, 40 nmol/L). A resumption of ovulatory cycles occurred when RU 486 concentrations were below 2.5 nmol/L. We conclude that in cynomolgus monkeys, inhibition of ovulation by RU 486 occurs mainly at the level of the hypothalamus, with possible additional effects on the granulosa cell function and alterations of LH bioactivity.

Animals↗
PubMed1995

Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis.

In many glomerular diseases severe injury to the mesangium may occur, leading to matrix dissolution and damage to the glomerular capillaries. Although the destruction of glomerular architecture may lead to permanent injury, in some cases spontaneous recovery occurs. The mechanisms that mediate this recovery are unknown. In this study we provide evidence for glomerular capillary repair (angiogenesis) in the adult injured glomerulus. Injection of anti-Thy 1 antibody into rats results in severe mesangiolysis with capillary ballooning, microaneurysm formation, and loss of endothelial cells in addition to mesangial cells. Although mesangial proliferation is a major response to injury, proliferation of endothelial cells also can be documented from days 2 to 14 in association with repair of the capillaries. The endothelial cell proliferation peaks on days 2 and 7, when it is seven- to ninefold greater than normal. Many of the endothelial cells display morphological features of angiogenesis. The initial wave of endothelial cell proliferation can be reduced by 40% with neutralizing anti-basic fibroblast growth factor antibodies (P < 0.001). The later glomerular endothelial cell proliferation is associated with upregulated expression of vascular permeability factor/endothelial cell growth factor (VPF/VEGF) and an increase of flk, a VPF/VEGF receptor. Although PDGF is expressed in this model, anti-PDGF antibody treatment did not affect the endothelial cell proliferative response. In summary, glomerular endothelial cells have an active role in the glomerular response to injury. Glomeruli are capable of healing microaneurysms, and the mechanism involves basic fibroblast growth factor- and VPF/VEGF-mediated endothelial proliferative responses.

Animals↗
PubMed1994

Hypothalamo-pituitary effects of RU486: inhibition of progesterone-induced hyperprolactinaemia.

Monkeys given oestrogen priming at physiological levels for at least 1 week become hyperprolactinaemic upon the addition of physiological progesterone administration. Here, using RU486, we test whether that this oestrogen/progestin-induced hyperprolactinaemia results from classical progesterone actions at the hypothalamo-pituitary level. Blood samples were collected daily from study day 1-67. Each monkey (n = 2) received daily injections of 25 micrograms/kg oestradiol benzoate, i.m., on study days 5-60. Progesterone-filled silastic capsules (3 cm) were inserted on study day 14 and removed on day 53. On study days 39-45, each monkey received RU486 (25 mg/day, p.o.). Serum samples were stored at -20 degrees C until assayed for prolactin, oestradiol, progesterone and RU486 by radioimmunoassay. Hyperprolactinaemia was induced in all three monkeys upon insertion of progesterone capsules. Prolactin concentrations fell sharply during RU486 treatment to nadirs some 10-fold less than prior to RU486 treatment. The time series was modelled by the Box-Jenkins autoregressive-integrated moving average (ARIMA) method with progesterone producing a gradual increase in prolactin concentrations and RU486 producing a sudden decrease. Statistically significant effects of progesterone and RU486 were found. Thus, the addition of progesterone to an oestrogenized milieu significantly increased prolactin concentrations, and RU486 fully reversed this effect. This evidence indicates that the progesterone-induced hyperprolactinemia in an oestrogenized milieu results from classical progesterone effects.

Animals↗