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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
PubMed1996

Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: a prospective study.

We studied 97 children who were weaned from antiepileptic drug therapy 1 year after their last seizure. Medication was withdrawn over 4 to 8 weeks, and patients were followed for 12 to 57 months (32.4 +/- 13.1; mean +/- SD) or until seizure recurrence. The overall probability of remaining seizure free was 78% at 3 months, 71% at 6 months, 66% at 12 months, and 61% at 24 months (95% CI, 51, 71), similar to studies that have required longer treatment periods. Factors retained in multivariate analysis were female sex, age at seizure onset over 120 months of age, seizure type, and clinical evidence of neurologic abnormalities. Using these risk factors, a simple method of predicting the 24-month recurrence risk was possible.

Anticonvulsants↗
PubMed1996

The effect of coculture on the postfertilization development of in vitro-matured monkey oocytes.

OBJECTIVE: To determine if the developmental potential of embryos resulting from in vivo- and in vitro-matured monkey oocytes could be increased through the use of a coculture system. DESIGN: Randomized prospective comparison of embryos resulting from either in vitro- or in vivo-matured oocytes cocultured with Vero cells or cultured in medium alone (control). SETTING: Basic research laboratory. MAIN OUTCOME MEASURES: In vitro embryo development to the blastocyst stage and blastocyst hatching. RESULTS: No significant difference in development was noted between coculture and control groups with embryos resulting from in vivo-matured oocytes. However, coculture was found to improve significantly the development of monkey embryos resulting from in vitro-matured oocytes. CONCLUSIONS: These results demonstrate that primate embryos resulting from in vitro-matured and in vitro-fertilized oocytes differ in their culture requirement when compared with embryos resulting from in vivo-matured oocytes.

Animals↗
PubMed1996

The molecular composition of neuronal microfilaments is spatially and temporally regulated.

The actin-based microfilament system is thought to play a critical role in neuronal development. We have determined specific changes in the composition of microfilaments accompanying neuronal morphogenesis. By using specific antibodies against the isoforms for tropomyosin (Tm) (Tm-5 and TmBr-1/-3) and actin (beta- and gamma-actin), we found that during early morphogenesis in vivo immature growing axons contain beta- and gamma-actin and Tm-5. In particular, Tm-5 is exclusively located in the immature axonal processes relative to the neuronal cell body. In contrast, beta-actin and Tm-5 are absent in mature, quiescent axons. This developmental loss from axons is associated with an approximately twofold downregulation of beta-actin and Tm-5 levels in the brain; gamma-actin levels do not change, and this molecule is widely distributed throughout neurons during development. The loss of beta-actin and Tm-5 from axons is accompanied by a progressive appearance of TmBr-1/-3. This apparent replacement of Tm-5 with TmBr-1/-3 occurs over a 2 d time period during rat embryonic hindbrain development and is conserved in evolution between birds and mammals. The loss of Tm-5 from axons involves a redistribution of this molecule to the cell soma and dendrites. These findings suggest that specialized microfilament domains are associated with the development and maintenance of neuronal polarity. We conclude that these Tm isoforms and beta-actin are subject to specific patterns of segregation associated with axonal development and neuronal differentiation. This provides a potential molecular basis for the temporal and spatial specificity of microfilament function during neuronal differentiation.

Actin Cytoskeleton↗
PubMed1995

Activation of the hypothalamo-anterior pituitary corticotropin-releasing hormone, adrenocorticotropin hormone and beta-endorphin systems during the estradiol 17 beta-induced plasma LH surge in the ovariectomized monkey.

The present work describes time-dependent changes in the content of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), and beta-endorphin (beta-EP) in the hypothalamus (HT) and anterior pituitary (AP) and in the concentration of ACTH and beta-EP in the plasma during the 17 beta estradiol (E2) benzoate (E2B)-induced luteinizing hormone (LH) surge in ovariectomized cynomolgus monkeys. Monkeys were euthanized at 0, 30, 48, 72, and 96 hr post-E2B. HT and AP were rapidly dissected, extracted in 2 N acetic acid containing 1 mM phenylmethane sulfonyl fluoride at 4 degrees C, and centrifuged at 18,000g for 30 min. Peptide concentrations were measured in the supernatant by specific radioimmunoassays (RIAs). In the HT, there were significant (P < 0.05) decreases in ACTH and beta-EP content by 30 hr post-E2B and a significant (P < 0.05) decrease in HT CRH content 48 hr post-E2B. Thereafter, CRH, ACTH, and beta-EP content increased up to 72 hr post-E2B. In the AP, there was an almost linear decrease in the CRH content through 48 hr post-E2B followed by a marked 20-fold (P < 0.01) increase in the AP CRH content at 72 hr post-E2B, which corresponds to the time of the descending arm of the LH surge. The patterns of ACTH and beta-EP content were very similar in the AP, while that of CRH differed markedly. In contrast, in the HT CRH, ACTH, and beta-EP profiles were very similar. Significant (P < 0.05) increases in circulating levels of ACTH, beta-EP, and cortisol were evident at 30 hr (all 3 hormones), 48 hr (beta-EP and cortisol), and 72 hr (cortisol) post-E2B, which corresponds with the time of decreased hypothalamic content of CRH, ACTH, and beta-EP. These results suggest that there maybe a marked activation of the hypothalamo-anterior pituitary-adrenal axis during the negative and positive feedback phases of the E2B-induced LH surge in the ovariectomized monkey.

Adrenocorticotropic Hormone↗
PubMed1995

Use of a spherical multiparameter transducer for flow cytometry.

Fused silicon dioxide, multiparameter flow transducers with 50 microns internal square cross section and approximately 60 microns length can simultaneously measure DC and RF impedance as well as fluorescence and multiple-angle light scattering. A spherical version of such a transducer was mounted in an EPICS CVA flow-cell housing and was installed on a research prototype equipped with an argon-ion laser. The signal that was produced by the spherical transducer with EPICS DNA-Check beads was 1.73 times greater than that produced with the standard cylindrical flow cell. Similarly, with EPICS Immuno-Brite beads, the average ratio was 1.96. The Coulter impedance and light-scattering measurements were similar to those produced with the conventional cylindrical outside flow cell, although the internal cross section of the sphere was square and that of the cylinder was circular. The theoretical arguments of Leif and Wells have been demonstrated to be correct. At present, monolithic, spherical fused-silica transducers are the optimal design for combined electrooptical, multiparameter flow cytometry analyzers.

Blood Cells↗
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

Prediction of ovarian response to exogenous gonadotropin stimulation: utilization for collection of primate oocytes for fertilization in vitro.

The predictive value of 2 tests for ovarian response to controlled ovarian hyperstimulation in the cynomolgus monkey model was evaluated. The tests utilized were: 1) the cycle Day 3 (Day 1 = onset of menses) FSH value and 2) the acute estradiol (E(2)) response to a GnRH agonists (GnRHa) administered on Day 3. Both tests were performed during the cycle preceding control ovarian hyperstimulation. Subsequently, monkeys (n = 26) were stimulated with Metrodin(T) (Days 2-6, 25IU/d) and Pergonal(T) (Day 7 to hCG administration, 25IU/d). Laparoscopic oocyte retrieval was performed 32 to 34 after hCG administration. Analysis of the data revealed that Day 3 FSH values could not predict whether an animal would respond well to control ovarian hyperstimulation in a subsequent cycle (P = 0.77). However, the E(2) change 24 h post-GnRHa administration was significantly greater for animals responding well to control ovarian hyperstimulation compared with the animals deleted after 6 d of stimulation (P = 0.042). The mean change in E(2) levels in animals taken to aspiration was 97.8 pg/ml compared with only 21.6 pg/ml for the deleted animals. This differential response of E(2) production after GnRHa treatment was used to correctly identify (by discriminant analysis) 78% of the animals subsequently deleted for poor response. Thus, the increase in serum E(2) level after GnRHa, but not the basal FSH level, was found to be predictive of ovarian response to stimulation in the cynomolgus monkey.

Journal Article↗
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↗