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Biomedical subjects

R W Brown

Publications and source records attributed to R W Brown.

At least 73 records · Page 4Linked to original sources
PubMed1996

The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development.

Glucocorticoids play important roles in development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed category of 11 beta-hydroxysteroid dehydrogenase type2 (11 beta-HSD2, which potently inactivates glucocorticoids) and the mineralocorticoid receptor (MR) by in situ hybridisation from embryonic day 9.5 (E9.5, term = E19) until after birth in the mouse. Widespread abundant 11 beta-HSD2 mRNA expression from E9.5-E12.5 changes dramatically at approximately E13 to a limited tissue-specific pattern (kidney, hindgut, testis/bile ducts, lung and a few brain regions (later seen in cerebellum, thalamus, roof of midbrain, neuroepithelial regions in pons and near the subicular hippocampus)). Placenta (labyrinthine zone) and extra-embryonic membranes express abundant 11 beta-HSD2 mRNA until E15.5 but this ceases = E16.5. It is unclear to what extent rodent term placental 11 beta-HSD activity is due to persisting 11 beta-HSD2 protein. Convincing MR mRNA expression is seen from E13.5 and includes pituitary, heart, muscle and meninges with expression later in gut, kidney, thymus, discrete areas of lung and several brain regions (including hippocampus, rhinencephalon and hypothalamus). 11 beta-HSD2 and MR clearly co-localise = E18.5 in kidney and colon and might do so in discrete areas of lung (E14-15) and neuroepithelia near the subicular hippocampus. Probably elsewhere MR are non-selective and 11 beta-HSD2 is involved in protecting glucocorticoid receptors in fetal fetal tissues. Comparison with previous enzymology studies suggest the changing pattern of 11 beta-HSD2 mRNA is likely to be translated into enzyme activity and have significant parallels in human development.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Localization of leukemia inhibitory factor in human endometrium during the menstrual cycle.

Leukemia inhibitory factor (LIF) has been shown to be imperative for the implantation of mouse blastocysts. The objective of this study was to examine the pattern of LIF protein in the human endometrium during the menstrual cycle. A low level of LIF was detected in endometrial glands during the proliferative phase. During the luteal phase, LIF staining in the glands appeared stronger in the mid- and late luteal phase than immediately after ovulation. However, a low level of LIF was detected in the stromal cells during the early and midproliferative phase, while only a minimal level was observed during the late proliferative and luteal phases.

Adult↗
PubMed1996

Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer.

The primary purpose of this study was to evaluate the prognostic significance of Ki-67, a cell proliferation-associated antigen, in a large group (n = 674) of axillary node-negative breast cancer cases with long-term follow-up and to correlate Ki-67 antigen expression with S-phase fraction. Ki-67 immunostaining was assessed both semiquantitatively and quantitatively. The statistical analysis focused on agreement between methods of Ki-67 quantification, agreement between Ki-67 and S-phase fraction, associations between Ki-67 and other clinical variables, and prognostic value of Ki-67. There was excellent agreement between the two methods of Ki-67 assessment (Spearman rank correlation, rsp = 0.91; P = 0.0001; n = 674) but only weak correlation between either semiquantitative or quantitative Ki-67 and S-phase fraction (rsp = 0.12 and rsp = 0.15, respectively). Ki-67 (overall median, 2%) was independent of tumor size and modestly related to other measures of tumor aggressiveness. Using a cutpoint of 5% (percentage of tumor cells), cases with high Ki-67 exhibited a significantly shorter disease-free survival (Padj = 0.004). In multivariate analysis, high Ki-67 was associated with a 1.8-fold increased risk of recurrence (P = 0.001). In the subgroup with S-phase data, the adjusted relative risk (hazard ratio, 1.9; P = 0.02) was unchanged by inclusion of S phase in the model. This suggests that Ki-67 provides significant independent prognostic information in addition to that contained in tumor size and S-phase fraction.

Breast Neoplasms↗
PubMed1995

Leu-7 immunoreactivity in cytologic specimens of thyroid lesions, with emphasis on follicular neoplasms.

Anti-Leu-7 (HNK-1, CD 57) antibody, a marker for natural killer lymphocytes, was employed by Ghali et al. (Hum Pathol 1992;23: 21-25) to study surgically resected formalin-fixed, paraffin-embedded thyroid lesions. They demonstrated strong immunoreactivity of this antibody with thyroid carcinomas, both follicular and papillary, and only occasional weak immunoreactivity with colloid goiters and follicular adenomas. We studied cytologic specimens (primarily fine-needle aspiration biopsy specimens) from 44 thyroid lesions, including 10 follicular carcinomas, 14 follicular adenomas, seven adenomatous nodules, six papillary carcinomas, and seven cases of Hashimoto's thyroiditis. All follicular carcinomas exhibited immunoreactivity to anti-Leu-7 antibody, usually of a moderate to strong degree (9/10); however, six of 14 follicular adenomas yielded similar results. The patterns of immunoreactivity in the other lesions were similar to those previously described (Ghali et al., Hum Pathol 1992;23:21-25). It does not appear that anti-Leu-7 antibody can be used as a specific marker of malignancy in the cytologic assessment of follicular neoplasms of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1995

Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy.

We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean +/- SD, 5.1 +/- 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), -45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 mL/cmH2O; 95%CI, -33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cm H2O/mL/s; 95%CI, -42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%CI, -27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRC, 99 vs. 138 mL/s; 95%CI, -54% + 2%; P = 0.04) as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Age Factors↗
PubMed1995

Densities of Ixodes ricinus ticks (Acari: Ixodidae) on moorland vegetation communities in the UK.

Unfed (questing) Ixodes ricinus ticks were collected by blanket dragging on a monthly basis from heather-dominated, Vaccinium-dominated and bracken-dominated vegetation communities from two different biogeographical regions of the UK (the Quantock Hills in Somerset, south west England and the North York Moors, north east England) throughout the spring and summer months of 1991 and 1992. Eighteen sites were monitored across the two regions and a total of 1920 blanket drags were carried out. Vaccinium sites showed high tick densities at all life stages, as did bracken sites. Significantly lower numbers of larval and nymphal ticks per drag were collected on heather sites than were collected on either Vaccinium (bilberry/whortleberry) or bracken sites, while similar numbers of adult ticks per drag were collected from each of the three vegetation communities. There was no significant difference between the mean numbers of any tick life stage collected on the Quantock Hills and those collected on the North York Moors on these vegetation communities or between the mean numbers of any tick life stage collected in 1991 and those collected in 1992 on these vegetation communities.

Animals↗
PubMed1995

Placental 11 beta-hydroxysteroid dehydrogenase and the programming of hypertension.

Excessive foetal exposure to glucocorticoids retards growth and "programmes" adult hypertension in rats. Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which catalyses the conversion of corticosterone and cortisol to inert 11 keto-products, normally protects the foetus from excess maternal glucocorticoids. In both rats and humans there is considerable natural variation in placental 11 beta-HSD, and enzyme activity correlates with birth weight. Moreover, inhibition of placental 11 beta-HSD in the rat reduces birth weight and produces hypertensive adult offspring, many months after prenatal treatment with enzyme inhibitors; these effects are dependent upon maternal adrenal products. These data suggest that placental 11 beta-HSD, by regulating foetal exposure to maternal glucocorticoids, crucially determines foeto-placental growth and the programming of hypertension. Maternal protein restriction during pregnancy also produces hypertensive offspring and selectively attenuates placental 11 beta-HSD activity. Thus, deficiency of the placental barrier to maternal glucocorticoids may represent a common pathway between the maternal environment and foeto-placental programming of later disease. These data may, at least in part, explain the human epidemiological observations linking early life events to the risk of subsequent hypertension. The recent characterization, purification and cDNA cloning of a distinct human placental 11 beta-HSD (type 2) will aid the further study of these intriguing findings.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Verumontanum mucosal gland hyperplasia.

Prostatic adenocarcinoma of the small acinar type can be mimicked by benign proliferative lesions, such as atypical adenomatous hyperplasia (adenosis), sclerosing adenosis, nodular hyperplasia (cellular areas), lobular hyperplasia, basal cell hyperplasia, mesonephric hyperplasia, and nephrogenic adenoma. In our study, we describe another microacinar proliferation, which we have termed verumontanum mucosal gland hyperplasia (VMGH) because it occurs exclusively in the verumontanum and adjacent posterior urethra where the ejaculatory ducts and utricle empty into the urethra. We reviewed 341 radical prostatectomies and cystoprostatectomies done from 1988 through 1993 for prostate and bladder carcinoma, respectively. Forty-nine prostates (14%) from patients aged 47 to 87 contained foci of VMGH. Of a total of 88 foci, a single lesion was present in 19 cases and multiple lesion in 30 cases. Fifty-nine of the foci arose around the ejaculatory or prostatic ducts, 17 from around the utricle, and 13 from adjacent posterior urethral mucosa. Individual lesions were quantified as to the number of acini per focus as follows: 6 to 10 in 28 (1+), 11 to 25 in 29 (2+), 25 to 50 in 16 (3+), and more than 50 in 15 (4+). No crystalloids or intraluminal mucin were seen, but; intraluminal corpora amylacea, usually numerous, were present in 57 of the 88 voci. The microacini were frequently "back to back" architecturally. The lining epithelium consisted of bland cuboidal to columnar luminal cells with underlying basal cells. VMGH, a previously undescribed benign microacinar proliferation, occurs in a very restricted and specific location and appears to be unrelated to other lesions with which it may be confused.

Aged↗
PubMed1995

Bronchiolitis obliterans in recipients of single, double, and heart-lung transplantation.

Thirty-two recipients of single, double, or heart-lung transplantation followed-up for at least 3 months posttransplant were retrospectively reviewed to assess the frequency, predictors, and risk factors associated with the development of bronchiolitis obliterans (BO). A clinical definition for the diagnosis of BO was made using the following criteria: persistent and progressive decline in FEF25-75, associated with normal results of cytologic and microbiologic studies for significant pathogens in bronchoalveolar lavage fluid, with a normal chest radiograph. This was correlated with histologic diagnosis and patient outcome. Sixteen (50%) of the patients developed BO, and this was associated with a 56% mortality. All but 1 patient with histologic BO had a clinical diagnosis of BO made (often months) prior to diagnostic biopsy. No patients with normal histologic findings had a clinical diagnosis of BO. More than 3 episodes of histologically documented acute rejections in any 12-month period were eventually associated with a 100% incidence of BO. Cytomegalovirus occurred with greater frequency in patients with BO, and in most cases, preceded or occurred concomitantly with the diagnosis of acute rejection or BO.

Adolescent↗
PubMed1995

p53 immunostaining in the differentiation of inflammatory pseudotumor from sarcoma involving the lung.

Inflammatory pseudotumor (IPT) of the lung is a non-neoplastic process that consists of proliferating spindle cells (fibroblasts and myoblasts), with variable numbers of mitoses, and inflammatory cells, particularly plasma cells. These lesions clinically, radiographically, and grossly mimic malignant neoplasms but are usually easily distinguished from malignancy on routine histopathology. However, in occasional cases the proliferating spindle cells may histopathologically mimic sarcoma, particularly on small biopsies and needle aspirates. Strong intranuclear immunopositivity for p53 protein is presumed to be indirect evidence of mutation of the p53 tumor suppressor gene and can be detected in many malignancies. In order to determine the utility of p53 immunostaining in differentiating IPT occurring in the lung from sarcoma involving the lung, we immunostained eight solitary IPTs, one IPT that recurred repeatedly over a 10-year period, six sarcomas (two malignant fibrous histiocytomas, two metastatic high-grade sarcomas, one metastatic alveolar soft part sarcoma, and one fibrosarcoma) involving the lung, and one IPT from which a sarcoma arose 10 years after radiation therapy. Immunohistochemistry was performed on 5-microns formalin-fixed sections using a commercially available antibody to the p53 protein (Biogenex, monoclonal 1:200) and a standard antigen retrieval technique. Weak intranuclear staining occurring in less than 10% of proliferating cells was not considered a true immunopositive. All eight of the solitary IPTs were immunonegative for p53 protein by our criteria. The IPT that recurred a number of times and the IPT from which a sarcoma later developed were also immunonegative for p53 protein. Four of the six sarcomas were immunopositive, as was the postradiation sarcoma arising from a p53-immunonegative IPT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Utility of microwave-citrate antigen retrieval in diagnostic immunohistochemistry.

Microwave heating of formalin-fixed, paraffin embedded tissue sections in citrate buffer (MHC) has been shown recently to enhance the antigenicity of a number of formalin-sensitive epitopes. To assess the practical utility of this technique in diagnostic immunohistochemistry, we evaluated the effect of MHC on the immunoreactivity of routinely processed tissue from the surgical pathology laboratory with 30 commonly applied, commercially available epithelial, mesenchymal, lymphoid, neuroendocrine, tumor, and prognostic markers. Paired tissue sections from a variety of normal and neoplastic tissues expected to contain the target antigen were immunostained in parallel following both the routine laboratory protocol, including protease digestion if indicated, and microwave heating for 10 min at maximum output in 10 mM citrate buffer without digestion. Slides were scored for intensity (1+ to 3+) and extent (1+, < 1/10; 2+, 1/10 to 1/3; 3+, 1/3 to 2/3; 4+, > 2/3) of immunostaining, and combined staining scores (intensity + extent) were calculated. Enhanced immunoreactivity compared to the routine protocol was observed with MHC for all 30 antibodies tested. The percentage of cases improved ranged from 38% to 100%, with a mean of 82%. The mean increase in staining score was 2.1. We concluded that MHC facilitates the recognition of diagnostically important antigens in formalin-fixed, paraffin-embedded tissue and can be applied routinely without adverse affects.

Antigens, Neoplasm↗
PubMed1995

Quantitative image analysis of MIB-1 immunoreactivity. A comparison with flow cytometric assessment of proliferative activity in invasive carcinoma of the breast.

Proliferative activity, especially flow cytometrically determined S-phase fraction, is generally accepted as an important prognostic indicator in carcinoma of the breast. We studied cellular proliferation in 53 breast carcinomas using quantitative image analysis of immunoreactivity to a recently available monoclonal antibody, MIB-1, which is applicable to formalin-fixed, paraffin-embedded tissues. MIB-1 is a murine monoclonal antibody that reacts with the Ki-67 nuclear antigen expressed by proliferating cells in the late G1, and G2/M phases of the cell cycle. These results were compared to flow cytometric determinations of S-phase and S + G2/M phase fractions obtained from corresponding fresh tissue samples. There was a good correlation between quantitative immunoreactivity to MIB-1 as measured by image analysis and flow cytometric S-phase and S + G2/M phase fractions (r = .63, P < .00001; r = .607, P < .00001, respectively). Immunoreactivity to MIB-1 and flow cytometric S-phase and S + G2/M phase fractions were significantly increased in aneuploid tumors as compared to diploid tumors. Histologic grade correlated with flow cytometric S-phase and S + G2/M phase fractions and MIB-1 immunoreactivity as determined by image analysis. There was a correlation between tumor size and MIB immunoreactivity. No proliferative parameters significantly correlated with lymph node status. Assessment of proliferative activity by quantitative image analysis of immunoreactivity to monoclonal MIB-1 antibody may be employed in cases of invasive carcinoma of the breast in which flow cytometric analysis fails to result in quantitative proliferative values, or it may be used as an alternative measurement of such proliferative activity.

Adenocarcinoma↗
PubMed1995

Diagnosis of chronic lung transplant rejection by transbronchial biopsy.

Chronic rejection in the form of obliterative bronchiolitis (OB) associated with chronic inflammation and fibrosis of bronchi (CIB) is a significant cause of morbidity and mortality in long-term heart-lung and single-lung transplant recipients. To determine the utility of transbronchial biopsy in diagnosing chronic rejection, we reviewed 24 transbronchial biopsies (TBBs) performed at the time of, or subsequent to, a clinical diagnosis of OB of chronic rejection in eight heart-lung and single-lung transplant recipients at the Methodist Hospital, Houston, Texas. These were compared with 36 randomly selected control TBBs from 14 patients without a clinical or histopathologic diagnosis of OB of chronic rejection at any time in their course. In the former group of TBBs, nine (38%) were diagnostic of OB and seven (29%) showed CIB suspicious for chronic rejection. TBBs diagnosed as negative had significantly fewer samples of tissue (1.0 versus > 3) and significantly smaller size of tissue (1.44 mm versus > 4.5 mm) than did TBBs in the OB or CIB categories. When strict criteria were used, no false diagnoses of OB of chronic rejection were made on control TBBs. However, OB associated with bronchiolitis obliterans organizing pneumonia of viral pneumonitis was present in three (8%) and CIB in 15 (42%) of control TBB associated with acute rejection and infection. This finding emphasizes the nonspecificity of CIB. We conclude that TBB is potentially useful in diagnosing OB of chronic rejection in some cases and in suggesting chronic rejection in other cases. Inadequate sampling by the bronchoscopist was the major reason for a negative biopsy.

Adolescent↗
PubMed1995

Quality of care for preschool children with asthma: the role of social factors and practice setting.

OBJECTIVE: To determine whether patient race or source of payment is associated with differences in the quality of inpatient and outpatient treatment for young children with asthma. DESIGN: Structured medical record review. SETTING: Tertiary care pediatric hospital. PATIENTS: We studied 354 patients aged 1 to 6 years discharged with asthma between October 1, 1989 and September 30, 1990. MEASURES: We developed indicators of the quality of asthma care provided before and during hospitalization and planned after discharge. Outpatient indicators were the use of inhaled beta-agonists and the use of preventive anti-inflammatory medications (inhaled steroids or cromolyn sodium) before admission. In-hospital indicators were the intensity of inhaled beta-agonist therapy in the emergency department and length of stay. Planning for post-hospital care was assessed by the prescription of a nebulizer for home use. We examined associations between these indicators and patient race and source of payment, and explored the influence of primary-care practice type on these associations. RESULTS: After adjustment for potential confounders, we found that Hispanic patients were less likely than white patients to have taken inhaled beta-agonists before admission. Both black and Hispanic patients were less likely than white patients to have taken anti-inflammatory medications. When we adjusted for the patients' primary-care practice type, the effect of patient race did not persist for these indicators of outpatient care. We found no differences by patient race in emergency department care or length of hospital stay. However, black and Hispanic patients were much less likely to be prescribed a nebulizer for home use upon discharge. After adjustment for confounders, there were no differences in the quality of asthma care by source of payment. CONCLUSIONS: We found that young children of racial minorities admitted for an asthma exacerbation were less likely to have received maximally effective preventive therapy. We also identified marked differences in the quality of care planned after hospital discharge for black and Hispanic patients, compared with white patients. Particularly in an era of health reform, attention should focus on barriers to high-quality care for underserved children, who are already at high risk for asthma-related morbidity.

Adrenergic beta-Agonists↗
PubMed1994

p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens.

To determine the utility of positive p53 protein immunostaining as an adjunct in the diagnosis of malignancy in pleural biopsy specimens, we reviewed 73 recently obtained pleural biopsy specimens that represented the typical range of diagnoses encountered in the evaluation of a proliferative pleural process. Immunohistochemistry was performed on paraffin sections of each biopsy specimen using a monoclonal antibody to the p53 suppressor gene product clone BP53-12 (BioGenex, San Ramon, CA) and a standard capillary gap (Microprobe, Fischer Scientific, Pittsburgh, PA) avidin-biotin complex technique with a citrate buffer antigen retrieval solution. Of the pleural biopsy specimens with unequivocal malignancy, 19 of 40 mesotheliomas and nine of 18 metastatic adenocarcinomas were immunopositive for p53 protein. All 13 of the biopsy specimens with reactive mesothelial hyperplasia or organizing pleuritis were negative. Two pleural biopsy specimens, which were interpreted as suspicious but inconclusive for malignancy, were positive for p53 protein and subsequent pathology specimens confirmed the presence of metastatic carcinoma in both of these biopsy specimens. Our findings suggest that p53 protein immunostaining is relatively sensitive and highly specific in differentiating reactive processes from primary or metastatic malignancies in histopathologically equivocal pleural biopsy specimens.

Adenocarcinoma↗