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Biomedical subjects

M C White

Publications and source records attributed to M C White.

At least 19 recordsLinked to original sources
PubMed1996

A comparative study of cytokine gene transcripts in normal and malignant breast tissue and primary cell cultures derived from the same tissue samples.

Using a differential centrifugation method followed by culture in selective medium, we have successfully isolated and maintained individual epithelial and stromal cells from normal (n = 10) and malignant (n = 6) human breast tissue and characterised their phenotype by immunocytochemistry. Further, we have studied expression of the cytokine genes IL-1beta, IL-6, IL-8 and TNF-beta in each cell fraction by RT-PCR and have compared these results with cytokine gene expression in tissue extracts from which primary cultures were derived. In breast tumours, there was near complete absence of IL-1beta in both whole tissue and cell fractions, and in normals it was present in only 3/10 tissue preparations, with increased expression in stromal (6/10) and epithelial (5/10) cell samples. IL-6 was constitutively expressed in all tumour-derived breast tissue samples but down-regulated in tumour cell cultures, with the opposite result in normal breast. Near identical levels of IL-8 expression were found throughout each preparation, irrespective of tissue origin. TNF-beta was expressed in all normal tissue samples, in 9/10 epithelial preparations but in only 6/10 stromal preparations. In tumours, TNF-beta was associated predominantly with whole tissue or stromal samples, with reduced expression in epithelial preparations. Our data confirm that primary cultures of normal and malignant human breast tissue can be successfully separated into epithelial and mesenchymal cell populations and their phenotype can be maintained in culture for up to 30 days. However, this cellular separation does alter the cytokine profiles; therefore, experimental findings with isolated cells should be treated with a caveat.

Base Sequence↗
PubMed1996

RT-PCR detection of cytokine transcripts in a series of cultured human meningiomas.

The expression of cytokine transcripts has been investigated in a series of cultured human meningiomas using reverse transcriptase linked polymerase chain reaction (RT-PCR), which allowed simultaneous analysis of a range of cytokines. The main histological subgroups of meningioma were investigated; these included transitional, fibroblastic, and syncytial as well as atypical meningiomas. Meningiomas from each of the different histological subgroups were subjected to a standard tissue culture regime. Total RNA was extracted from representative cultures and reverse-transcribed to yield cDNA. PCR was performed using oligonucleotide primers designed to detect interleukin (IL)-1 alpha/beta to IL-8, transforming growth factor (TGF)beta 1-3, tumour necrosis factor (TNF)alpha/beta, and interferon (IFN)gamma. Transcripts for IL-3, IL-6, IL-8, and TGF beta 3 were detected in all cultures. Transcripts for the three isomers of TGF beta were expressed in the transitional and fibroblastic meningioma cells. TGF beta 2 and TGF beta 3 transcripts were expressed in the syncytial and TGF beta 1 and TGF beta 3 in the atypical meningioma cells. IL-1 beta transcripts were expressed in fibroblastic and atypical cultures and TNF beta transcripts were expressed in syncytial and transitional cultures only. Transcripts for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF alpha, or IFN gamma were not detected in any of the meningioma cultures. This investigation using cells cultured from a small number of tumours from each of the classic histological subtypes suggests that there is a distinct pattern of cytokine mRNA expression linked with histological classification.

Cytokines↗
PubMed1996

Tuberculosis mortality associated with AIDS and drug or alcohol abuse: analysis of multiple cause-of-death data.

The resurgence in tuberculosis morbidity in the mid-1980s has increased interest in tuberculosis mortality. We examined mortality in the United States, from tuberculosis in 1990, using multiple cause-of-death data to describe the impact of AIDS and substance abuse, defined as drug or alcohol abuse, on mortality from tuberculosis. Tuberculosis mortality by age showed a bimodal pattern, with a peak between ages 25 and 55; by race/ethnicity, black and Hispanic males had the highest mortality rates, and black females had rates close to those of Hispanic males. Although in each of the race/ethnicity categories the removal of deaths with AIDS resulted in mortality curves closer to those of 1980, the bimodal pattern remained for black and Hispanic deaths. When we examined deaths with tuberculosis and substance abuse, we found that substance abuse without AIDS may account for additional deaths contributing to the bimodal pattern seen.

AIDS-Related Opportunistic Infections↗
PubMed1996

Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas.

OBJECTIVE: The human pituitary gland is affected selectively by conditions associated with iron deposition, but the mechanisms for this are unknown. In this study we have determined whether the transferrin receptor, which mediates iron uptake by cells, could be detected immunocytochemically in human pituitary adenomas in vitro. PATIENTS: Data were derived from 35 patients undergoing transsphenoidal surgery and included 13 with clinically non-functioning adenomas, 15 with acromegaly, 4 prolactinomas, 2 patients with Cushing's disease and one patient with Nelson's syndrome. MEASUREMENTS: Transferrin receptor immunopositivity was determined for each adenoma in dispersed cell culture using a specific monoclonal antibody. RESULTS: Eight of 13 clinically functionless adenomas showed immunopositive transferrin receptor expression, whilst adenomas from 15 patients with acromegaly, 4 prolactinomas, 2 Cushing's syndrome and one patient with Nelson's syndrome were negative. The eight transferrin receptor positive tumours were gonadotrophinomas and accounted for eight of the nine tumours which secreted and immunostained for FSH; all eight also secreted and immunostained for LH. CONCLUSIONS: These findings may reflect a special requirement for iron by gonadotrophin secreting cells in comparison to other pituitary cell types and this could underlie the reasons why in the normal pituitary these cells are especially susceptible to malfunction in iron overload syndromes such as genetic haemochromatosis and beta-thalassaemia.

Adenoma↗
PubMed1995

Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool Diabetic Eye Study.

OBJECTIVE: To evaluate different methods for community based screening for sight threatening diabetic eye disease. DESIGN: Prospective study. SETTING: Mobile screening unit visiting inner city community clinics; hospital assessment clinic (tertiary centre). SUBJECTS: 395 diabetic patients registered with four general practices in an inner city location. INTERVENTIONS: Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist, both compared with reference standard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease. MAIN OUTCOME MEASURES: Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease (moderate preproliferative retinopathy, circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes related eye disease). RESULTS: 358 subjects underwent photography, 326 attended hospital clinic for ophthalmoscopy, and six were ungradable on photographs and biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic within four months of photography. Sensitivity of detection of eye disease by photography was 89% (95% confidence interval 80% to 98%), significantly better than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93% by addition of stereoscopic macular pair photographs. Specificity of detection of sight threatening eye disease was 86% (82% to 90%) for photography and 97% (95% to 99%) for direct ophthalmoscopy. CONCLUSIONS: Since high sensitivity is essential for an effective screening programme, a photographic method should be considered as preferred option in national, community based screening programmes. Even in the hands of an experienced ophthalmologist, direct ophthalmoscopy is limited by weaknesses inherent to the instrument.

Ambulatory Care↗
PubMed1995

1 alpha,25-dihydroxyvitamin D3 analogs featuring aromatic and heteroaromatic rings: design, synthesis, and preliminary biological testing.

Aromatic compounds 2a-c, analogs of 1 alpha, 25-dihydroxyvitamin (calcitriol, 1), and heteroaromatic compounds 4a-c and 5a-c, analogs of 19-nor-1 alpha, 25-dihydroxyvitamin D3 (3), were designed to simulate the topology of their biologically potent parent compounds while avoiding previtamin D equilibrium. Convergent and facile total syntheses of the analogs (+)-2b, (+)-2c, (-)-4b, and (-)-5b were achieved via carbonyl addition of regiospecifically formed organolithium nucleophiles to the enantiomerically pure C,D-ring ketone (+)-17, characteristic of natural calcitriol (1). Likewise, hybrid analogs 20a-c were prepared to determine whether incorporation of a known potentiating side chain would lead to increased biological activity. Preliminary in vitro biological testing showed that aromatic analogs (+)-2b, (+)-2c, and 20a-c as well as heteroaromatic analogs (-)-4b and (-)-5b have very low affinities for the calf thymus vitamin D receptor but considerable antiproliferative activities in murine keratinocytes at micromolar concentration. No biological advantage was observed in this keratinocyte assay for the doubly modified hybrid analogs 20a-c over the singly modified parent (+)-2b. Analog (+)-2b, but surprisingly not the corresponding analog 20b differing from (+)-2b only in the side chain, showed considerable activity in nongenomic opening of calcium channels in rat osteosarcoma cells.

Animals↗
PubMed1995

Interleukin-3: a putative protective factor against breast cancer which is secreted by male but not female breast fibroblasts.

The enzyme 17 beta-hydroxysteroid dehydrogenase (17-HSD) is a key regulator of intracellular 17 beta-estradiol (E2), which is associated with breast cancer and is influenced by paracrine factors released by breast-cancer fibroblasts. Since the incidence of breast cancer is much higher in females than in males, we have used an in vitro cell culture system to investigate whether male fibroblasts may inhibit breast-cancer genesis by restricting the intracellular accumulation of E2. Fibroblasts were obtained from normal males and females undergoing reduction mammoplasty, and from females with benign or malignant breast lesions. Fibroblast-conditioned medium (CM) was incubated with the established breast-cancer cell line, MCF-7, and its effects on 17-HSD activity were assessed. CM (25% v/v) from male breast fibroblasts had a significant inhibitory effect on reductive 17-HSD, decreasing E2 production. This was in direct contrast to the effects of CM from female breast fibroblasts, which had a powerful stimulatory effect on reductive 17-HSD. RT-PCR allowing simultaneous detection of a range of cytokines was performed on each type of fibroblast. IL-3 mRNA was consistently detected in fibroblasts from male but not female breast tissue. Addition of rhIL-3 to cultures of MCF-7 caused a reduction in 17-HSD activity and addition of a polyclonal antibody directed against IL-3 to male CM completely reversed the inhibitory effects of CM. Thus, male breast fibroblasts may be responsible for secreting IL-3-like factors which, given the considerably lower incidence rates of breast cancer in men, may have a protective effect against breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1995

Effects of urban air pollutants on emergency visits for childhood asthma in Mexico City.

The metropolitan area of Mexico City, Mexico, has serious air pollution problems. Although air contaminants may contribute to clinical asthma, there are at present no data on the relation between air pollution exposure and childhood asthma in Mexico City. The authors reviewed data on emergency visits from January to June 1990 at one major pediatric hospital in Mexico City. They used a Poisson regression model to study the relation between the number of daily emergency visits for asthma and air pollutant levels. The levels of ozone and sulfur dioxide-exposure were significantly associated with the number of emergency visits for asthma. After adjustment for potential confounding factors, the multivariate regression model predicted that an increase of 50 ppb in the 1-hour maximum ozone level would lead to a 43% increase in the number of emergency visits for asthma on the following day. Exposure to high ozone levels (> 110 ppb) for 2 consecutive days increased the number of asthma-related emergency visits by 68 percent. The results of this study suggest that ozone exposure is positively associated with the number of children's emergency visits for asthma in Mexico City.

Adolescent↗
PubMed1995

Isolated adrenocorticotropin deficiency presenting as primary infertility.

A 31 year old female presented with primary infertility and gave a two year history of amenorrhea without symptoms or signs of endocrine dysfunction. Examination was normal and investigation showed low oestradiol and progesterone levels with decreased LH pulsatility. The cortisol responses were impaired following hypoglycaemic stress and a short synacthen test, but the cortisol response to a prolonged synacthen test was normal. An inadequate ACTH response to CRF testing confirmed the diagnosis of isolated ACTH deficiency. Hydrocortisone therapy was followed by an ovulatory menstrual cycle. Amenorrhea again ensued following the reduction of the steroid dose and normal menses resumed on normal steroid replacement therapy. Six hourly gonadotrophin pulsatility showed a significant increase in both pulse amplitude and mean LH and FSH levels following steroid treatment. Isolated ACTH deficiency is a rare but treatable cause of hypogonadism and infertility, and this case gives further insight on the role of cortisol on the hypothalamo-pituitary gonadal axis.

Adrenocorticotropic Hormone↗
PubMed1995

Urinary catheter-related infections among home care patients.

Urinary catheterization is a common indication for home care nursing services among older adults, and catheter-related urinary tract infections commonly occur among these patients. The purpose of this study was to determine the rate of urinary catheter-related infections among a group of elderly adults cared for in the home, the characteristics of those who acquire urinary tract infections as opposed to those who do not become infected, and the influence of the interval between catheter changes on the incidence of urinary tract infections.

Aged↗
PubMed1995

Effects of quinagolide (CV 205-502), a selective D2-agonist, on vascular reactivity in patients with a prolactin-secreting adenoma.

BACKGROUND: Quinagolide (CV 205 502) is a dopamine D2-receptor agonist which has proved effective in the treatment of prolactinomas, reducing both serum PRL and tumour size. Some of its D2-receptor effects are mediated via alpha-adrenoceptors, which have a major influence on the control of vascular tone. The aim of this study was to examine the influence of quinagolide on in-vivo dorsal hand vein vascular responses to noradrenaline in patients with a prolactinoma. DESIGN AND PATIENTS: Seven female patients with prolactinomas (age 37 (28-46) years), intolerant of bromocriptine, were studied before and after 3 months treatment with quinagolide (0.75-1.5 mg/day). Patients were otherwise disease free, were taking no other medication, and had been on no other medication (including bromocriptine) for at least 3 months prior to enrollment into the study. MEASUREMENTS: Vascular responses to locally infused noradrenaline were measured in dorsal hand veins using an established technique. PRL, oestradiol, FSH, LH, blood pressure and body mass index were also measured before and after 3 months treatment. RESULTS: Quinagolide significantly reduced PRL in all 7 patients (1795 (696-4680) (mean (range)) vs 488 (290-868) mU/l, P = 0.001), with no effect on the other parameters, including mean arterial pressure (88 (2) vs 87 (4) mmHg, P = 0.6). Vascular reactivity to noradrenaline was significantly increased after 3 months therapy: log10 dose estimated to cause 50% vasoconstriction (ED50) 1.37 (0.12) vs 0.85 (0.12) ng/min (P = 0.003; a lower ED50 indicates less noradrenaline is required to constrict the vein by 50%). CONCLUSIONS: Vasoconstrictor responses to noradrenaline were increased in all patients after 3 months treatment with quinagolide. Peripheral veins carry alpha-adrenoceptors analogous to those of systemic resistance vessels. If this increased vasoconstrictor response in patients with prolactinomas was occurring in hypophyseal vessels, it would lead to reduced tumour blood supply. Quinagolide may therefore reduce tumour blood flow, which may be one factor responsible for its effectiveness in these patients.

Adult↗
PubMed1995

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Adenoma↗
PubMed1995

Effect of glycoprotein and protein hormones on human meningioma cell proliferation in vitro.

Speculation that meningiomas are subject to female hormone influence is supported by their higher incidence in women and reports of exacerbation of symptoms during pregnancy and the luteal phase of the menstrual cycle. Previous reports have concentrated on the effects of the steroid hormones oestradiol and progesterone on meningioma proliferation. In this study we have investigated the roles of the glycoproteins LH, FSH and human chorionic gonadotrophin (hCG), and the protein hormones prolactin (PRL) and human placental lactogen (hPL) on the proliferation of human meningiomas in vitro. The three glycoproteins had an inhibitory effect on meningioma proliferation ranging from 5.0-50.0%, 10.0-63.0% and 2.4-34.0% at the highest concentrations of LH (25 mIU/ml), FSH (15 mIU/ml) and hCG (30 IU/ml) respectively. Cultures were also treated with PRL (100 and 200 ng/ml) and hPL (5 and 10 ng/ml) and the protein hormones had a stimulatory effect on cell proliferation of 12.0-55.5% and 11.4-73.6% when treated with 200 ng/ml PRL and 10 micrograms/ml hPL respectively. Our data suggest that increasing levels of the protein hormones PRL and hPL, falling levels of hCG and the absence of LH and FSH in the second and third trimesters of pregnancy may play a role in the acceleration of meningioma growth in these stages of pregnancy.

Adult↗
PubMed1995

Angina, functional impairment and physical inactivity among Mexican-American women with depressive symptoms.

There has been a long-standing interest in the relationship between cardiovascular disease (CVD) and psychiatric morbidity, specifically depressive symptoms. The aims of this study were to determine the following: 1. The relationship between the presence of angina and depressive symptoms; 2. The influences of sociodemographic covariates on this relationship; and 3. The effects of functional impairment or inactivity level in mediating the relationship between angina and depressive symptoms. The data utilized for this study was from the Hispanic Health and Nutrition Examination Survey (HHANES) on 1,558 Mexican American women. The survey was cross sectional, conducted in 1982-84. The dependent variable was depression as measured by the Center for Epidemiologic Depression Scale (CES-D). The independent variable was the presence of angina as measured by the Rose Questionnaire. Covariates included functional impairment, physical activity, age, education, acculturation, poverty level, marital status, and work status. The findings suggest that functional impairment has a stronger association with depressive symptoms than angina or physical inactivity. Significant sociodemographic variables include single marital status and poverty. Comorbidity has been a neglected area of research for Mexican American women, but this study suggests that functional impairment is a more important factor associated with depressive symptomatology than angina.

Activities of Daily Living↗
PubMed1994

Interleukin-6 (IL-6) production and cell growth of cultured human ameningiomas:-interactions with interleukin-1 beta (IL-1 beta) and interleukin-4 (IL-4) in vitro.

We examined the production of interleukin (IL)-6 by human meningioma cells in vitro, and the effects of IL-1 beta and IL-4 on IL-6 production and meningioma cell growth. The histological classification of the tumours studied included transitional, syncytial, fibroblastic and atypical. All 10 meningiomas studied produced IL-6 (range 0.22-7.6 ng/ml/10(6) cells/24 h). Separate addition of IL-1 beta or IL-4 to cultures increased IL-6 production up to ten fold, and two to three fold, respectively. Growth studies with IL-6 indicated that this cytokine significantly increased terminal cell density at a concentration greater than 1 ng/ml in 60% of the meningioma cultures studied. IL-1 beta caused a significant decrease in the terminal cell density in 25% of the meningioma cultures studied whereas IL-4 had a tendency to significantly inhibit growth in 16.6% of the cultures. These data suggest that IL-6 production by meningiomas can be modified by other cytokines and secondly, that IL-6, IL-1 beta and IL-4 can modify growth in vitro and may act as autocrine factors in vivo. By further determining the cytokine profiles within meningiomas and their effects, a better understanding of meningioma growth characteristics may be obtained.

Cell Division↗
PubMed1994

Exacerbations of childhood asthma and ozone pollution in Atlanta.

Asthma prevalence and mortality due to asthma have been increasing during the last decade, and both the rates and the increases in rates have been higher for blacks than whites and higher for children than adults. Whether environmental factors such as air pollution contribute to these increases is unknown. The purpose of this study was to examine the relationship between emergency visits to a hospital for childhood asthma and exposure to ozone in an indigent, predominantly black population. Data were collected by abstracting clinical records for all children with asthma or reactive airway disease in one public hospital during the summer of 1990. From June 1, 1990, to August 31, 1990, 609 visits were made by children aged 1 to 16 years to an emergency clinic for treatment of asthma or reactive airway disease. Monitoring data indicated that maximum ozone levels equalled or exceeded 0.11 ppm on 6 days during the study period. The average number of visits for asthma or reactive airway disease was 37% higher on the days after those 6 days (from 6:00 PM to 6:00 PM the next day) than on other days (95% CI, RR = 1.02-1.73). The results of the study suggest that among black children from low-income families, asthma may be exacerbated following periods of high ozone pollution.

Adolescent↗
PubMed1994

Surveillance of intravenous catheter-related infections among home care clients.

BACKGROUND: Infection control in home care is an important area of study, and infection related to home infusion therapy is one component. METHODS: According to billed supplies from a 6-month period, we identified clients receiving intravenous care and conducted a chart review to determine characteristics and infection status. We reviewed each client from the start of a continuous home care period through April 30, 1992. RESULTS: Care of the catheters was done by nurses, family care givers, or the clients themselves. Intravenous catheter-related infections-site infections and bacteremia-occurred in three (4.5%) of the sample of 67; bacteremia occurred in one (1.5%). Incidence density was 12.5 infections per 10,000 catheter days (4.2 bacteremias per 10,000 days). Among those with central lines who remained without infection, 22.9% had the same line in place for 90 days or more. Among those with peripheral lines who remained without infection, 14.3% had a peripheral line, which was changed during home care, for 30 days or longer. CONCLUSIONS: Home care agencies seeking accreditation from the Joint Commission on the Accreditation of Healthcare Organizations need to establish surveillance systems; this may be one method to monitor device-related infections and to determine baseline rates.

Adolescent↗