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Biomedical subjects

L M Marshall

Publications and source records attributed to L M Marshall.

At least 19 recordsLinked to original sources

Reproducibility of the University of Toronto self-administered questionnaire used to assess environmental sensitivity.

Environmental sensitivity patients report symptoms provoked by low-level exposure to a wide range of substances. Features of published case definitions include nature of onset, chronicity, symptom provocation by multiple substances, symptom provocation by an escalating number of exposures, involvement of multiple body systems including the nervous system, provocation by unrelated substances, and addictive behaviors. This study assessed the reproducibility of a Canadian self-administered questionnaire, the University of Toronto Health Survey, designed to determine the prevalence of the features described in these case definitions. A total of 191 eligible respondents aged 16-70 years who attended several types of medical practices in 1994 were invited to complete a second questionnaire 5-7 months after the first; 134 (70.2%) complied. Total agreement on whether patients satisfied each of seven case definitions ranged from 80% to 90%. After adjustment for chance, major agreement was observed for three of the seven case definitions (kappa = 0.69, 0.68, and 0.78). The survey achieved good reproducibility regarding self-report of symptoms described in published case definitions of environmental sensitivity.

Adolescent↗

Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study.

OBJECTIVE: To determine the extent to which uterine leiomyomas are associated with characteristics of pregnancy, labor, and neonatal outcome recorded on birth certificates. METHODS: In a population-based series of women who delivered singleton live infants in Washington state from 1987-1993, we linked computerized birth certificates and hospital discharge records to investigate the relationship between uterine leiomyomas and complications in pregnancy and delivery. Subjects were 2065 women with uterine leiomyomas noted on computerized hospital discharge records. From the remaining records, a comparison group of women without uterine leiomyomas diagnoses were selected at random and frequency-matched by birth year to women with leiomyomas. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of pregnancy or delivery complications in relation to uterine leiomyomas after multivariate adjustment. RESULTS: Women with leiomyomas were more likely than controls to be over age 35 at delivery, nulliparous, or black. We observed independent associations between uterine leiomyomas and abruptio placentae (OR 3. 87, 95% CI 1.63, 9.17), first trimester bleeding (OR 1.82, 95% CI 1. 05, 3.20), dysfunctional labor (OR 1.85, 95% CI 1.26, 2.72), and breech presentation (OR 3.98, 95% CI 3.07, 5.16). The risk of cesarean was also higher among women with uterine leiomyomas (OR 6. 39, 95% CI 5.46, 7.50), but a portion of the excess risk might have been due to biased detection of leiomyomas at cesarean delivery. CONCLUSION: Leiomyomas appear to increase likelihood of complications during pregnancy, labor, and delivery.

Adult↗

Epidemiologic contributions to understanding the etiology of uterine leiomyomata.

Uterine leiomyomata are hormonally dependent tumors that are a major source of gynecologic morbidity among women of reproductive age. Relatively few studies have attempted to identify specific risk factors for these neoplasms. In this review of epidemiologic contributions to the etiology of uterine leiomyomata, we begin by outlining methodologic issues in epidemiologic studies that arise from the fact that a large proportion of uterine leiomyomata does not come to medical attention. We then review the major findings from published epidemiologic studies, which to date have focused primarily on menstrual and childbearing history, exogenous hormone use, obesity, cigarette smoking, and other lifestyle and behavioral characteristics that may in part reflect aspects of a woman's hormonal milieu. None of the potential risk factors studied have demonstrated sufficiently consistent associations to guide decisions on the primary prevention of uterine leiomyomata. Clarifying the etiology and natural history of uterine leiomyomata will require studies designed to address methodologic issues and test hypotheses involving environmental and lifestyle influences on endocrine function, as well as on other possible etiologic mechanisms. Recent advances in molecular genetics present opportunities for epidemiologic studies of uterine leiomyomata to incorporate biomarkers of somatic changes found in these tumors and to examine inherited genetic factors related to possible causal physiologic mechanisms.

Disease Progression↗

Regulation of polyphosphate kinase gene expression in Acinetobacter baumannii 252.

A strain of Acinetobacter baumannii cultured in butyric acid media was found to take up phosphate following a period of phosphate release. PCR was used to clone the polyphosphate kinase (ppk) gene from the strain. The promoter for the ppk gene was functional in the heterologous Escherichia coli host. Using RT-PCR, transcription of the ppk gene was found to be regulated by phosphate concentration.

5' Untranslated Regions↗

A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata.

OBJECTIVE: To investigate the risk of uterine leiomyomata in relation to reproductive factors and oral contraceptive use. DESIGN: A prospective study. SETTING: A cohort of female registered nurses from 14 states in the United States who completed mailed questionnaires in 1989, 1991, and 1993. PATIENT(S): Premenopausal nurses (n=95,061) aged 25-42 years with intact uteri and no history of diagnosed uterine leiomyomata or cancer in 1989. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of self-reported uterine leiomyomata confirmed by ultrasound or hysterectomy. In a sample of 243 cases, 93% of the self-reported diagnoses were confirmed in the medical record. RESULT(S): During 326,116 person-years of follow-up, 3,006 cases of uterine leiomyomata, confirmed by ultrasound or hysterectomy, were reported. After adjustment for other risk factors, the risk of uterine leiomyomata was significantly inversely associated with age at menarche, parity, and age at first birth, and positively associated with a history of infertility and years since last birth. The only notable association with any aspect of oral contraceptive use was a significantly elevated risk among women who first used oral contraceptives at ages 13-16 years compared with those who had never used oral contraceptives. CONCLUSION(S): Reproductive factors and oral contraceptive use at a young age influence the risk of uterine leiomyomata among premenopausal women.

Adult↗

Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking.

To investigate whether factors influencing ovarian function affect risk of uterine leiomyomata, we examined prospectively the association of new diagnoses confirmed by ultrasound or hysterectomy with body mass index, weight change, height, and cigarette smoking among 94,095 premenopausal women with intact uteri, who were ages 25-42 years at the start of follow-up in 1989. We assessed body mass index and cigarette smoking from responses on the study questionnaire completed just before diagnosis. During 322,775 person-years, 2,967 new cases of uterine leiomyomata confirmed by ultrasound or hysterectomy were reported. Risk among all cases confirmed by ultrasound or hysterectomy increased with increasing adult body mass index. The multivariate relative risks (RR) and 95% confidence intervals (CI) according to body mass index categories of <20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and > or =30.0 were 0.90 (95% CI = 0.79-1.03), 1.00 (referent), 1.08 (95% CI = 0.97-1.21), 1.16 (95% CI = 1.03-1.31), 1.21 (95% CI = 1.05-1.40), 1.36 (95% CI = 1.16-1.59), and 1.23 (95% CI = 1.09-1.39), respectively. The RRs for hysterectomy-confirmed cases generally were higher. Similarly, risk was positively associated with weight gain since age 18 years. Body mass index at age 18 years, height, and cigarette smoking were unrelated to risk of uterine leiomyomata. Elevated adult body mass index is associated with a modest increased risk of uterine leiomyomata among premenopausal women.

Adult↗

Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.

OBJECTIVE: To quantify the incidence of uterine leiomyoma confirmed by hysterectomy, ultrasound, or pelvic examination according to age and race among premenopausal women. METHODS: From September 1989 through May 1993, 95,061 premenopausal nurses age 25-44 with intact uteri and no history of uterine leiomyoma were followed to determine incidence rates of uterine leiomyoma. The self-reported diagnosis was confirmed in 93% of the medical records obtained for a sample of cases. Using pooled logistic regression, we estimated relative risks (RRs) of uterine leiomyoma according to race and examined whether adjustment for other potential risk factors could explain the variation in the race-specific rates. RESULTS: During 327,065 woman-years, 4181 new cases of uterine leiomyoma were reported. The incidence rates increased with age, and the age-standardized rates of ultrasound- or hysterectomy-confirmed diagnoses per 1000 woman-years were 8.9 among white women and 30.6 among black women. After further adjustment for marital status, body mass index, age at first birth, years since last birth, history of infertility, age at first oral contraceptive use, and current alcohol consumption, the rates among black women were significantly greater for diagnoses confirmed by ultrasound or hysterectomy (RR 3.25; 95% confidence interval [CI] 2.71, 3.88) and by hysterectomy (RR 1.82; 95% CI 1.17, 2.82) compared with rates among white women. We observed similar RRs when the cohort was restricted to participants who reported undergoing a screening physical examination within the 2 years before baseline. CONCLUSION: A higher prevalence of known risk factors did not explain the excess rate of uterine leiomyoma among premenopausal black women.

Adult↗

Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types.

Epidemiological studies using the histological classification of Page for benign breast disease consistently demonstrate a positive association between atypical hyperplasia and the subsequent development of breast cancer. However, atypical hyperplasia is of either lobular or ductal types, and breast cancer risk in relation to type of atypical hyperplasia has not been studied extensively. Thus, we investigated prospectively the risk of breast cancer associated with histological subtypes of benign proliferative breast disease, including the types of atypical hyperplasia, among participants in the Nurses' Health Study who had biopsy-confirmed benign breast disease. Women who subsequently developed breast cancer were matched by year of birth and year of biopsy to participants who were free from breast cancer. Benign biopsy slides were classified according to the criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs), adjusted for the matching variables and other breast cancer risk factors, were computed using unconditional logistic regression with benign nonproliferative breast disease as the referent group. Atypical ductal hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR = 5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast cancer risk. Atypical lobular hyperplasia was more strongly associated with the risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2). The association of atypical ductal hyperplasia and breast cancer risk varied little by menopausal status. The magnitude of breast cancer risk seems to vary according to the type of atypical hyperplasia present at biopsy.

Adult↗

Reactive cell change in cervicovaginal smears.

Reactive cell change in cervicovaginal smears is a controversial issue. The most common criteria for reactive cell change include an increase in nuclear size, presence of nucleoli, binucleation, cytoplasmic vacuolization, and polychromasia. The purpose of this study is to define, as specifically as possible, the criteria of reactive cell change. Sixty-one cervicovaginal smears in a routine examination obtained during 1988 to 1994 were reviewed for this study. All cases had been diagnosed as reactive. Fifty-three of these were re-diagnosed as reactive and 8 cases were rediagnosed as negative. Inflammatory cells were present in 79% and organisms involvement such as Herpes, Trichomonas, Chlamydia, Gardnerella, and Candida were present in 23% percent. The smears were also evaluated for cellular arrangement, origin of the reactive cells, and presence of nucleoli. The majority of reactive cells were found in aggregates and were of metaplastic origin. Nucleoli were present in 85% of the cases. In all cases the most important criteria of reactive cell change were found to be aggregates of metaplastic cells with central nuclei containing nucleoli and a fine chromatin pattern, followed by the presence of organisms. Additionally, the majority of cases with a cytology diagnosis of reactive cell change had a squamous intraepithelial lesion on biopsy. In conclusion, this study suggests that follow-up Pap smears over a two year period may revert to normal in some of the cases.

Adolescent↗

Healthy young and old women differ in their trunk elevation and hip pivot motions when rising from supine to sitting.

OBJECTIVE: To describe the differences between healthy young and older women in regards to trunk elevation and hip pivot motions when rising from a supine to a seated position. DESIGN: Cross-sectional comparison. SETTING: University laboratory. PARTICIPANTS: Two groups of healthy female volunteers: young adult female controls (n = 22, mean age 23.5 years) and community-dwelling older female adults (n = 17, mean age 73.8 years). MEASUREMENTS: Subjects were videotaped as they performed three controlled bed mobility tasks, starting from a supine position: (1) rising to a seated position at the edge of a firm plinth surface (SS); and rising to a seated position without moving to the edge of the bed while either (2) using hands (SUH) or (3) not using hands (SUNH). A series of movements involving the trunk were identified as subjects performed the SS task. RESULTS: The older women were more likely to rotate and laterally flex their trunks, particularly in the later phases of the SS task. In addition, during the SS task, the older group was more likely to bear weight on their hip/gluteal area, particularly in the later phases, and more likely to use a broad pivot base, consisting of the hip and the elbow. While all young and old performed the SUH task, less than half of the older group could complete the SUNH task. Moreover, the subgroup of older adults who could not complete the SUNH task may have accounted for much of the differences between the young and the old on the SS task. CONCLUSION: Healthy young and older women differ in their ability to rise from a supine to sitting position, primarily in the strategies used to elevate the trunk and facilitate a pivot. Trunk flexion ability likely contributes to the age group differences noted in rising. These data provide the basis for a biomechanical analysis of the critical body segment motions and the strengths required to perform bed mobility tasks.

Adult↗

Aerosol deposition in cystic fibrosis using an aerosol conservation device and a conventional jet nebulizer.

The deposition of technetium radiolabelled aerosol within the lungs of 12 stable cystic fibrosis patients (mean age 12.7 years) was compared using the Acorn nebulizer and mouthpiece alone, and the Acorn nebulizer attached to the Mizer Aerosol Conservation Device (MACD). The total activity delivered to the patient using the MACD was 11.1% (+/- 7.8% s.d.) of the initial dose, compared to 5.8% (+/- 4.2% s.d.) with the nebulizer and mouthpiece alone (P < 0.05). With the MACD, 84% of the intrapulmonary dose was delivered to the peripheral regions, compared to 76.5% with the nebulizer and mouthpiece (P < 0.05). No significant correlation was found between aerosol deposition and pulmonary function. The Mizer Aerosol Conservation Device significantly increases both total intrapulmonary aerosol deposition and peripheral aerosol distribution.

Adolescent↗

Different synaptic channel kinetics in sympathetic B and C neurons of the bullfrog.

Sympathetic ganglia of the frog contain two types of principal neurons, B and C cells, which are innervated by two distinct classes of cholinergic preganglionic axons, B and C fibers. This study examined and compared the kinetics of nicotinic ACh-gated channels that produce the fast excitatory postsynaptic currents (EPSCs) in B and C cells. Neurons were identified and voltage-clamped at -50 mV, 22 degrees C. The EPSC decayed as a single exponential for both cell types, but the decay time constants differed considerably; 10.2 +/- 2.3 msec (mean +/- SD) for C cells and 5.5 +/- 1.1 msec for B cells. Analysis of ACh-induced membrane current fluctuations revealed spectra that fit single-Lorentzian functions and gave estimates of the mean channel open time of 9.8 +/- 2.0 msec and 5.2 +/- 0.9 msec for C and B cells, respectively. Thus, the clear difference in EPSC decay rate for these two types of ganglion cells is most likely due to the differences in the mean lifetimes of their synaptic channels.

Acetylcholine↗

Innervation of small intensely fluorescent cells in frog sympathetic ganglia.

Autonomic ganglia have a population of small intensely fluorescent (SIF) cells with unknown function. We have investigated the afferent innervation of SIF cells in bullfrog sympathetic ganglia using intracellular recordings and light microscopy of stained preganglionic axon terminals. Contrary to previous knowledge, bullfrog SIF cells do indeed receive functional synaptic input and this innervation is provided solely by the C-type preganglionic nerve fibers.

Animals↗

Lack of nicotinic supersensitivity in frog sympathetic neurones following denervation.

The sensitivity of bull-frog sympathetic neurones to nicotinic, cholinergic agonists has been studied in both normal (control) and surgically denervated ganglia. Using gross extracellular recording, the sensitivity to acetylcholine (ACh) increased 18-fold following denervation, while that to carbachol (CCh) was unchanged. Normal ganglia showed a similar sensitivity increase after inhibition of cholinesterase. This suggests that the rise in ACh sensitivity is due to reduced cholinesterase activity, not to true supersensitivity. There was no significant difference in resting membrane potential or input resistance between normal and denervated neurones. Neurones denervated for 7-50 days showed no significant change in sensitivity to ACh or CCh applied iontophoretically at a distance of 10 micron from the cell surface. In control ganglia, localized iontophoretic application of ACh revealed an uneven distribution of sensitivity which is attributed to the localization of receptors to synaptic areas. Fourteen days after denervation, the geometric mean sensitivity to focally applied ACh was not significantly different from that found in control ganglia. The variation in sensitivity to focally applied ACh at randomly chosen sites on denervated neurones was as great as that found in control ganglia. It is concluded that denervation does not cause frog sympathetic neurones to become supersensitive to ACh. The apparent increase in nicotinic ACh sensitivity observed using extracellular recording from whole ganglia is due not to a change in the number or distribution of ACh receptors, but to a decrease in cholinesterase activity.

Acetylcholine↗

Exclusion of erythrocyte-specific membrane proteins from clathrin-coated pits during differentiation of human erythroleukemic cells.

When human erythroleukemic cells are induced to differentiate, they produce globin and redistribute glycophorin and spectrin to one pole of the cell. This process was accompanied by an alteration in the clathrin-coated pits at the cell surface. In nondifferentiating cells, receptors for Concanavalin A have been shown, using electron microscopy, to be concentrated into coated pits and rapidly internalized. Glycophorin was also internalized via coated pits, but was not greatly concentrated into these portions of the surface membrane. Ligands attached to glycophorin were, therefore, cleared from the cell surface more slowly than Concanavalin A. In nondifferentiating cells, immunoelectron microscopy showed that spectrin is largely excluded from coated pits. After erythroid differentiation proceeded for several days, glycophorin was totally excluded from the coated pits along with spectrin. This did not reflect a general cessation of endocytosis, however, because Concanavalin A receptors continued to be internalized. It is possible that the specific exclusion of glycophorin from coated pits is part of the remodeling process that occurs when the precursor cell membrane differentiates into that of the mature erythrocyte.

Cell Differentiation↗

Protein and glycoprotein synthesis by Friend erythroleukaemic cells during erythroid differentiation.

The proteins synthesized by Friend erythroleukemic cells (line 707 B) have been studied by high-resolution polyacrylamide gel electrophoresis at various stages after the induction of erythroid differentiation by addition of dimethyl sulphoxide to the medium. After 24 h of differentiation, the rate of synthesis of most of the more abundant proteins is reduced, correlating with the reduction in the proliferation rate of the cells. However, the qualitative composition of the major proteins synthesized by control and differentiating cells remains very similar until at least 96 h after the induction of differentiation. Proteins characteristic of the mature erythrocyte membrane are an exception to the reduction in synthesis in line with the proliferation rate, for they continue to be synthesized at similar rates to those found in control cells. Only two major proteins (an as yet unidentified cytoplasmic protein and globin) are reproducibly induced, while the synthesis of a few proteins is almost completely abolished. In contrast to the similarity of the synthesis of the major proteins in the control and differentiating cells, the synthesis of glycoproteins that bind to Concanavalin A is markedly changed. The synthesis of many Concanavalin A-binding glycoproteins is abolished and they disappear from differentiating cells. The synthesis of a major glycoprotein is, however, induced early in differentiation. This protein, which has an apparent molecular weight of 100,000, becomes the most abundant Concanavalin A-binding glycoprotein in the cell.

Actins↗

Synaptic localization of alpha-bungarotoxin binding which blocks nicotinic transmission at frog sympathetic neurons.

Sympathetic neurons receive direct synaptic input from cholinergic terminal boutons of preganglionic nerve fibers. The distribution of acetylcholine receptors at these synapses is not precisely known. This study shows that alpha-bungarotoxin, which binds specifically to nicotinic receptors on skeletal muscle, also may be useful for localizing postsynaptic nicotinic receptors on principal neurons in the paravertebral sympathetic ganglia of the bullfrog. alpha-Bungarotoxin (1-5 microM) produces a block of nicotinic (fast) excitatory postsynaptic potentials that is fully reversed after 5-8 hr of washing. Dihydro-beta-erythroidine, a nicotinic antagonist, reduces the half-time of recovery from the toxin block to one-third of the control value, presumably by competing for the same receptor sites. Furthermore, the response to applied carbachol is reduced by the toxin, indicating that the block of synaptic transmission is due to a decreased response of the postsynaptic membrane. Peroxidase-labeled alpha-bungarotoxin is localized to small (0.2- to 0.5-micrometers diameter) patches beneath synaptic boutons. Peroxidase reaction product is restricted to regions of the synaptic cleft just opposite the active zones of the presynaptic terminal. In addition, peroxidase-labeled antibodies against Torpedo acetylcholine receptor bind exclusively to these same synaptic regions; evidently these patches are the areas at which nicotinic receptors are concentrated at synaptic contacts on sympathetic neurons.

Animals↗