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Biomedical subjects

L M Nelson

Publications and source records attributed to L M Nelson.

At least 19 recordsLinked to original sources

Gonadotropins enhance HLA-DR antigen expression in human granulosa cells.

OBJECTIVES: To determine whether HLA-DR expression in the human ovary is controlled by endocrine or immune mediators, we examined the effects of several lectins, lymphokines, and hormones on granulosa cells in vitro. STUDY DESIGN: HLA-DR antigens were detected by indirect immunofluorescence on granulosa cells obtained at oocyte retrieval for in vitro fertilization. RESULTS: When cultured with concanavalin A, pokeweed mitogen, phytohemagglutinin, interleukin-1, or interleukin-2, granulosa cells failed to express HLA-DR antigens. Both interferon alfa and interferon beta induced only a modest expression of HLA-DR molecules (4.1% +/- 0.9% and 2.5% +/- 0.8%, respectively) in comparison with the marked increase in HLA-DR expression (25.2% +/- 2.8%), when granulosa cells were exposed to interferon gamma. The gonadotropins follicle-stimulating hormone and human chorionic gonadotropin alone were unable to induce HLA-DR antigens, but acted synergistically with interferon gamma to enhance expression in a dose-dependent manner. The addition of 0.1 and 10 IU/ml of follicle-stimulating hormone with 10,000 IU/ml of interferon gamma significantly increased expression by 11.5% +/- 2.5% and 15.5% +/- 2.7%, respectively, over that of interferon gamma alone. Similarly, 1 and 10 IU/ml of human chorionic gonadotropin produced a 7.8% +/- 2.0% and 12.4% +/- 2.2% increase in HLA-DR expression over baseline. CONCLUSION: These studies demonstrate that factors from both the immune and endocrine systems can interact to control HLA-DR expression in the ovary.

Adult

Spontaneous abortion and subsequent adverse birth outcomes.

OBJECTIVE: Our purpose was to evaluate the association between spontaneous abortion and subsequent adverse birth outcomes. STUDY DESIGN: Washington State birth certificate records for 1984 to 1987 were used to examine the association between spontaneous abortion and adverse outcomes in the subsequent live birth. Adverse birth outcomes were examined for women with one spontaneous abortion before the index pregnancy (n = 2146) and for women with three or more prior spontaneous abortions and no other prior pregnancies (n = 638); compared with women with no prior spontaneous abortions (n = 3099). Logistic regression was used to estimate the relative risk associated with prior spontaneous abortion of each adverse outcome. RESULTS: Women with three or more prior spontaneous abortions were at higher risk for delivery at less than 37 weeks' gestation (relative risk 1.5, 95% confidence interval 1.1 to 2.1), placenta previa (relative risk 6.0, 95% confidence interval 1.6 to 22.2), having membranes ruptured greater than 24 hours (relative risk 1.8, 95% confidence interval 1.2 to 2.9), breech presentation (relative risk 2.4, 95% confidence interval 1.6 to 3.6), and having an infant with a congenital malformation (relative risk 1.8, 95% confidence interval 1.1 to 3.0). CONCLUSION: These findings suggest that common causes may underlie recurrent spontaneous abortion and certain adverse birth outcomes. They may also help guide clinical management of pregnancies in women with a history of recurrent spontaneous abortions.

Abortion, Spontaneous

Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial.

OBJECTIVE: To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Tertiary care research institution. INTERVENTIONS: Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. PATIENTS, PARTICIPANTS: Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. MAIN OUTCOME MEASURES: We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. RESULTS: The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Adult

Influence of metribuzin on the Rhizobium leguminosarum--lentil (Lens culinaris) symbiosis.

The effects of the triazine herbicide metribuzin (Sencor) on the lentil (Lens culinaris Medic.) - Rhizobium leguminosarum biovar viciae symbiosis were studied in Leonard jars and growth pouches. Lentils inoculated with Rhizobium leguminosarum strain 128C54 or 128C84, and noninoculated lentils grown in plant nutrient solution supplemented with 5 mM KNO3, had metribuzin applied to the plants at either 8 or 13 days after planting. When sprayed at 8 days, metribuzin had a significant (p less than or equal to 0.05) negative effect on plant weight, number of nodules, taproot growth, and acetylene reduction activity. Five to 10 days after spraying, the plants began to recover from the inhibitory effects. When spraying was delayed to 13 days after planting, metribuzin had little effect on plant growth. The R. leguminosarum strain used as inoculant affected the degree of inhibition of lentil growth and the rate of plant recovery. Less than 0.2% of foliarly applied metribuzin was translocated to the root. Thus the detrimental effects of metribuzin application to lentils were mainly due to direct effects on the plant, which resulted in indirect effects on nodulation and nitrogen fixation.

Fabaceae

Cigarette smoking, alcohol use, and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention. METHODS: We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age- and gender-matched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type. RESULTS: Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (greater than 20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (less than or equal to 20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% CI, 3.7-13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (greater than 2 drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension. CONCLUSIONS: Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage.

Adult

Baclofen effect on quadriceps strength in multiple sclerosis.

Weakness has been reported by patients as one side effect of baclofen. We evaluated torque production as a measure of contractile strength in 30 subjects with clinically definite multiple sclerosis. Participants, with minimal to moderate spasticity, were titrated onto baclofen by 5mg increments every other day for seven days and maintained at 20mg for one week. Using a KinCom isokinetic unit set at 60 degrees per second, subjects performed maximal concentric quadriceps contractions; three consecutive trials were recorded. Results indicated no significant difference in maximum torque production between sessions. Although torque values remained unchanged, the angle at which peak torque production occurred moved closer to normal values. Subjective reports of weakness do not appear related to physiologic properties of contraction, but may be a subjective interpretation that less stiffness is weakness because of less resistance to muscle contraction.

Activities of Daily Living

Hypotheses to explain the association between vigorous physical activity and amyotrophic lateral sclerosis.

Many epidemiologic studies indicate a relation between vigorous physical activity and amyotrophic lateral sclerosis. Physical activity itself is unlikely to cause amyotrophic lateral sclerosis, but could it modify the effects of other etiologic factors such as neurotoxins? Vigorous physical activity could potentiate the effect of a toxin to motor neurons by any of several mechanisms, especially if the toxin's effects were mediated through excitation. Exercise could alter the extent of exposure or could influence the distribution, metabolism or potency of an excitotoxin. Future epidemiologic studies of amyotrophic lateral sclerosis should include sufficient detail about vigorous physical exercise to explore this relationship further.

Amyotrophic Lateral Sclerosis

Increased peripheral T lymphocyte activation in patients with karyotypically normal spontaneous premature ovarian failure.

OBJECTIVE: To determine if soluble interleukin 2 (IL-2) receptor measured in serum by an enzyme-linked immunosorbent assay (ELISA) might be useful in managing patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, controlled observation. SETTING: Tertiary care research institution. INTERVENTIONS: None. PATIENTS, PARTICIPANTS: Twenty-four patients with karyotypically normal spontaneous premature ovarian failure comprised the study group. Forty-two healthy men and women comprised the normal reference group. MAIN OUTCOME MEASURES: We measured peripheral T lymphocyte human leukocyte antigen locus-DR (HLA-DR) expression and IL-2 receptor expression using monoclonal antibodies and flow cytometry. We measured soluble IL-2 receptor levels in serum using an ELISA. RESULTS: Consistent with previous findings, our patients had significantly higher HLA-DR expression on peripheral T lymphocytes (5.3 +/- 0.46) as compared with controls (3.5 +/- 0.34) (mean +/- SEM, P less than 0.01). Seven patients also had elevated IL-2 receptor expression on peripheral T lymphocytes (P less than 0.05). However, soluble IL-2 receptor levels in the serum did not differ significantly from normals. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure have a modest increase in peripheral T lymphocyte activation measured by flow cytometry. This degree of activation does not result in increased soluble IL-2 receptor release measured by ELISA.

Autoantibodies

Evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis.

Thirty men and women diagnosed with definite multiple sclerosis (MS) were treated for ten weeks in a blinded, cross-over study. Patients with minimal to moderate spasticity were randomized to one of three sequences to evaluate the effects on MS-related spasticity of baclofen alone, stretching regimen with placebo, placebo alone, and stretching regimen with baclofen. The Cybex II isokinetic unit, timed gait, Ashworth scale, and subject's assessment of function were objective and subjective measures used to evaluate changes in hypertonicity. There was significant correlation between the Cybex and Ashworth as methods of measuring spasticity. Overall, treatment with baclofen alone significantly improved moderate quadriceps spasticity as measured by Cybex flexion scores. A trend, indicative of enhancing the beneficial effects of baclofen, was noted when stretching exercises were added to the treatment.

Adult

Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy.

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.

Animals

Fluorescent detection of rabbit endometrial implants resulting from monodispersed viable cell suspensions.

A model for early stage endometriosis was prepared in rabbits by intraperitoneal injection of monodispersed viable endometrial cells. With this model, we have found that DHE fluorescence increases the sensitivity of detection of endometrial tissue. The potential experimental and clinical significance of ectopic endometrial detection by porphyrin fluorescence is enhanced by the recent report of endometrial transplant destruction by PDT. Although caution must be exercised for extrapolation from animal experiments to human conditions, these results encourage further evaluation of photosensitization for the study and potential treatment of disorders involving endometrial tissue.

Animals

Multiple sclerosis sibling pairs: clustered onset and familial predisposition.

We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS. Age- and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls. A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls. In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members. Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.

Adult

Efficacy of assisted reproductive technology during diagnostic and operative infertility laparoscopy.

Women being evaluated for infertility were offered assisted reproductive technology at the time of diagnostic laparoscopy. Oocyte retrieval was performed after ovulation induction in 33 women, of whom 19 had concurrent operative laparoscopy. Gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF) and embryo transfer were performed subsequently depending on laparoscopic assessment of pelvic architecture, oocyte maturity, and semen parameters. The clinical pregnancy rate was 24% per cycle and 28% per gamete or embryo transfer (four pregnancies after GIFT and four after IVF/embryo transfer). The clinical pregnancy rate per transfer did not differ significantly between the 19 women who had therapeutic operations in conjunction with laparoscopy (lysis of adhesions and/or fulguration of endometriosis) and the 13 who did not (25 versus 30%; P greater than .05). Assisted reproductive technology can be performed successfully during diagnostic infertility laparoscopy. Operative endoscopic manipulation did not adversely influence pregnancy outcome.

Adult