Search PubMed⌕ Search

Biomedical subjects

R W Brown

Publications and source records attributed to R W Brown.

At least 91 records · Page 5Linked to original sources
PubMed1994

High doses of oral contraceptives do not alter endometrial alpha 1 and alpha v beta 3 integrins in the late implantation window.

OBJECTIVE: To assess the effects of an emergency contraceptive agent on the distribution of integrin heterodimers during that part of the implantation window. DESIGN: Prospective, case-controlled study in a university-based Population Program. In the first ovulatory control cycle after the detection of LH surge, patients had endometrial sampling 11 days after the surge. In the next cycle the procedure was repeated 2 days after the administration of a postcoital contraceptive agent on day 9 after LH surge (100 g ethinyl E2 and 2 mg norgestrel). MAIN OUTCOME MEASURES: The effects of postcoital contraceptives on the expression of integrin heterodimers (alpha 1 and alpha v beta 3 subunits) reported to be unique to secretory phase was determined. RESULTS: All six specimens were consistent histologically with days 24 and 25 of the menstrual cycle by light microscopy. Using immunohistochemistry, strong membrane staining of endometrial glandular cells and superficial epithelium for both alpha 1 subunit and vitronectin (alpha v beta 3) receptor was observed in treatment and controls. No diminution of intensity or distribution was observed relative to pretreatment controls. CONCLUSIONS: There is no apparent change in the level of these two integrins in the human endometrium when high-dose oral contraceptives are given in the later stages of the implantation window. This suggests that the high doses of steroids used in emergency contraceptives may exert their effect through more complex mechanisms than endometrial cell surface changes.

Contraceptives, Oral↗
PubMed1994

Isolated vasculitis involving the female genital tract: clinicopathologic spectrum and phenotyping of inflammatory cells.

Isolated vasculitis involving the female genital tract (IVF) is rare. Although both giant cell arteritis (GCA) and polyarteritis nodosa (PAN) types of involvement have been documented, several clinicopathologic features of IVF are not clearly understood. We wish to report two cases of IVF (one GCA and one PAN) and compare them with previously reported cases. Including our two cases, we found a total of 33 reported cases of IVF, which included 18 GCA and 15 PAN. In cases of GCA, all parts of the female genital tract were involved with roughly comparable frequency, whereas in the case of PAN, the cervix is uniformly involved, with the vulva and myometrium being affected once and twice, respectively. In all cases of GCA and most cases of PAN, the vasculitis represented an incidental finding upon microscopic examination of the female genital tract removed for unrelated problems; however, in one case of PAN, vaginal bleeding probably related to vasculitis-induced cervical ulcer was reported. In either category, no clearcut pattern of predisposing factors was identified and, at the time of diagnosis, none of the patients had any diseases known to be associated with vasculitis, such as connective tissue disease, rheumatoid arthritis, or drug hypersensitivity. Although antineutrophilic cytoplasmic antibodies were recently described as sensitive and specific markers for systemic vasculitis, tests for these antibodies were not done on previously reported cases and were negative for both current cases. Long-term follow-up in IVF indicates that even without any specific treatment for vasculitis, systemic involvement did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Assessment of Ki-67-derived tumor proliferative activity in colorectal adenocarcinomas.

Analysis of tumor growth fraction (TGF) has become essential as cell cycle-directed modalities have been increasingly used for the treatment of solid neoplasms. We studied TGF in fresh tissue samples from 74 surgically resected colorectal carcinomas (50 colon and 24 rectum; 44 men and 30 women) by flow cytometry (FCM) and by immunostaining using Ki-67 monoclonal antibody. In 12 cases, samples of uninvolved colonic mucosa adjacent to tumor (transitional mucosa) and samples of normal mucosa (at least 5 cm away from tumor) were available for growth fraction analysis. The mean Ki-67 and S-phase values were 17.1% (range, 0-60%) and 17.5% (range, 3-39%), respectively. The mean percentage of Ki-67 positivity in tumor samples from women was significantly lower than that in samples from men (P = 0.001). Ki-67-derived TGF values, however, did not correlate with patient age, lymph node status, or tumor size, site, stage, degree of differentiation, or DNA ploidy. The correlation between Ki-67-derived and FCM-derived TGF values was statistically significant (P = 0.001) but marginal (R = 0.35). In both transitional and normal colonic mucosa samples, Ki-67 positivity was mainly confined to the lower half of the crypts, and their growth fraction values were significantly lower than those of tumor tissue; however, there was no difference in values between transitional and normal mucosae. Our results indicate that Ki-67-derived TGF does not correlate with known prognostic factors for colorectal carcinoma; however, long-term follow-up information will be necessary to define the clinical value of Ki-67 staining.

Adenocarcinoma↗
PubMed1993

Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer.

BACKGROUND: The p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells. Most p53 mutations result in a nonfunctional protein that accumulates in tumor cell nuclei. These common mutations appear to be involved in the development and/or progression of several neoplastic diseases including human breast cancer. PURPOSE: Our purpose was to investigate the relationships between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer. METHODS: Expression of mutant p53 protein was evaluated by frozen-section immunohistochemistry (IHC) and light microscopy in 700 breast cancers from axillary lymph node-negative patients with long-term follow-up (median, 54 months). The immunostaining signal was expressed as the sum of scores representing the proportion and staining intensity of negative and positive tumor cell nuclei (ranges, 0 and 2-8, respectively). Statistical comparisons were made between levels of p53 protein expression and disease-free survival, overall survival, and tumor proliferation rate expressed as the percentage of cells in the S phase (%S phase) as determined by flow cytometry. RESULTS: Of the 700 tumors, 362 (52%) showed positive nuclear immunostaining (IHC score > 0). Proliferation rates were significantly higher (P = .0001) in positive tumors (median %S phase, 7.1%) than in negative tumors (4.1%). In a univariate cutpoint analysis, negative tumors (n = 388) versus low-positive tumors (IHC score = 2-6; n = 263) versus high-positive tumors (IHC score > 6; n = 99) showed progressively reduced disease-free survival (80% versus 72% versus 58% at 5 years, respectively; P < or = .05 for all pairwise comparisons). Analogous results for overall survival were 88% versus 84% versus 74%; only the result for negative versus high positive tumors was significant (P = .003). In a multivariate analysis, expression of p53 protein and high %S phase were independently associated with reduced disease-free survival (P = .008 and .01, respectively). CONCLUSIONS: Expression of mutant p53 protein was associated with high tumor proliferation rate, early disease recurrence, and early death in node-negative breast cancer. Despite the strong direct correlation between accumulation of p53 protein and tumor proliferation rate, both factors were independently associated with poor prognosis, suggesting that p53 may have other biological functions in addition to cell-cycle regulation. IMPLICATIONS: This test, when combined with other prognostic factors, may enhance our ability to identify node-negative breast cancer patients at high risk for early disease recurrence and/or death, for whom the use of adjuvant chemotherapy is unequivocally justified.

Adult↗
PubMed1993

Predicting RF field penetration in heterogeneous bodies using a 3-D finite element approach: preliminary results.

We present preliminary results for a 3D finite element calculation to evaluate RF penetration in conducting dielectric materials at high field strengths. A tetrahedral mesh is used along with a Coulomb gauge constraint in a finite element method that yields excellent numerical stability at high frequencies. Accuracy is verified by comparisons with analytic solutions for single-layer and multiple-layer heterogeneous systems and for a 3D spherical model. We have also compared the finite element model with experimental results presented by Foo et al., Magn. Reson. Med. 23, (1992). Agreement is very good and argues for the usefulness of the method in the calculation of RF penetration and RF power deposition effects in heterogeneous objects.

Animals↗
PubMed1993

Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma.

The diagnostic distinction between malignant pleural epithelial mesothelioma and pulmonary adenocarcinoma is often difficult and partially reliant on the use of immunohistochemistry (IHC). While there are several available IHC markers preferentially expressed in adenocarcinomas compared with mesotheliomas, there are no readily available or well-validated markers preferentially expressed in mesotheliomas and no markers are absolutely specific for either tumor. Thus, there always will be an element of doubt regarding the identity of lesions diagnosed by IHC using these markers and an undesirable reliance on negative results if the lesion is truly a mesothelioma. To help optimize the ability of currently available but imperfect markers to resolve adenocarcinoma and mesothelioma and to minimize the impact of false-negative results on their diagnosis, a systematic study was undertaken to identify multiple-marker immunostaining phenotypes that are the most specific and sensitive for each type of tumor. The study involved staining a series of malignant epithelial mesotheliomas (n = 34) and pulmonary adenocarcinomas (n = 103) with eight markers that were selected on the basis of previous reports of their relatively restricted specificities for one or the other of these lesions (and included carcinoembryonic antigen [CEA], tumor-associated glycoprotein 72 [B72.3], Leu-M1, vimentin, thrombomodulin, secretory component, carcinoma antigen-125, and periodic-acid-Schiff with diastase [for mucin]. Considering the markers one, two, and three at a time, all possible combinations of results were analyzed by computer to identify the phenotype most sensitive and specific for adenocarcinoma or mesothelioma. The best single marker was CEA (positive: 97% specific and sensitive for adenocarcinoma; negative: 97% specific and sensitive for mesothelioma). However, because examples of both tumor types expressed CEA, none of the study cases were unequivocally resolved and the risk of false-negative results was relatively high. The best two markers were CEA and B72.3 (both positive: 100% specific and 88% sensitive for adenocarcinoma; both negative: 99% specific and 97% sensitive for mesothelioma). The four possible combinations of results for these two markers resolved 68% of cases (93 of 137 cases), with less risk of false-negative results than a single marker. In general, several three-marker panels resulted in sensitivities and specificities similar to the two-marker panel of CEA and B72.3. In particular, the three-marker panel of CEA, B72.3, and Leu-M1 resulted in eight possible phenotypes that resolved 74% of cases (101 of 137 cases), with even further reduced risk of false-negative results.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Amplification of ribulose biphosphate carboxylase/oxygenase large subunit (RuBisCO LSU) gene fragments from Thiobacillus ferrooxidans and a moderate thermophile using polymerase chain reaction.

Southern blot analysis of DNA from an iron-oxidising moderate thermophile NMW-6 and from Thiobacillus ferrooxidans strain TFI-35 demonstrated sequences homologous to the RuBisCO LSU gene of Synechococcus. DNA fragments (457 bp) encoding part of the RuBisCO LSU gene (amino acids 73-200) were amplified from the genomic DNA of Thiobacillus ferrooxidans and the moderate thermophile NMW-6 using the polymerase chain reaction (PCR) technique (Saiki et al. (1985) Science 233, 1350-1354). A comparison with the LSU sequences from T. ferrooxidans, Alcaligenes eutrophus, Chromatium vinosum, Synechococcus and Spinacea oleracea, which all have RuBisCOs with a hexadecameric structure, showed that the RuBisCO LSU gene sequence from NMW-6 appeared to be most closely related to that of the hydrogen bacterium A. eutrophus which showed 71.9% homology at the amino acid level. Despite its physiological similarity, T. ferrooxidans showed only 64.1% homology to the amino acid sequence from NMW-6 and had the lowest DNA homology (60.9%) of the hexadecameric type RuBisCOs. In the region sequenced, T. ferrooxidans and the RuBisCOs of the phototrophs C. vinosum, Synechococcus and S. oleracea, had 17 residues that were completely conserved which were substituted in both NMW-6 and A. eutrophus, 11 of these being identical substitutions. Comparison of the nucleotide and derived amino acid sequences of the RuBisCO LSU fragment from T. ferrooxidans with other RuBisCO sequences indicated a closer relationship to the hexadecameric type LSU genes of photosynthetic origin than to that of A. eutrophus. The T. ferrooxidans amino acid sequence showed 93.8%, 78.9% and 77.3% homology, respectively, to the C. vinosum, Synechococcus and S. oleracea (spinach) sequences but only 56.2% to A. eutrophus. The DNA sequence from Rhodospirillum rubrum, which has the atypical large subunit dimer RuBisCO structure with no small subunit, showed 39.2% and 42.7% homology, respectively, with the sequences of NMW-6 and T. ferrooxidans, and 25.0% and 29.7% amino acid homology, indicating that the DNA homology was substantially random in nature. PCR fragments (126 bp) that overlaped the last 15 codons of the fragments above were also amplified and sequenced. They showed incomplete homology with the larger fragments, supporting evidence obtained from Southern hybridizations that T. ferrooxidans and the moderate thermophile NMW-6 have multiple copies of RuBisCO LSU genes.

Amino Acid Sequence↗
PubMed1993

Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life.

The relationship between initial level of lung function and subsequent wheezing, lower respiratory illness (LRI) was studied in 97 infants in whom the first measurement of pulmonary function (PFT) was made before 6 months of age. Occurrence of LRI was evaluated by standardized questionnaires at each well-baby visit, biweekly telephone calls to mothers, and review of all visits to physicians. Infant PFT was assessed by partial expiratory flow-volume curves and helium-dilution measurement of functional residual capacity (FRC). Maternal, prenatal smoking was assessed by urine cotinine and standard questionnaires. Infants who developed an LRI during the first year of life had lower preillness length-corrected forced expiratory flow at FRC (VFRC) than those who did not experience an LRI (males, 2.06 +/- 0.20 versus 2.32 +/- 0.29 ml/s/cm; females, 2.38 +/- 0.20 versus 2.91 +/- 0.26 ml/s/cm). Similar results were observed with FRC-corrected VFRC. No differences were observed for FRC. Differences in lung function were greatest in female infants whose mothers did not smoke during pregnancy (VFRC 2.67 +/- 0.25 versus 3.49 +/- 0.26 ml/s/cm for those with and without LRI, respectively; p = 0.03). History of maternal wheezing was more common in infants who experience an LRI, independent of maternal smoking. The results were not influenced by exposure to nonmaternal sources of environmental tobacco smoke in the postnatal period. Regression analyses that included data for multiple measurements of VFRC over the first year and took account of duration of follow-up demonstrated that lower levels of VFRC were associated with an increased frequency of LRI, especially in female infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1993

Giant cell interstitial pneumonitis. Disease recurrence in the transplanted lung.

Recurrence of the original disease in the transplanted organ is well reported in renal transplant recipients. There have been no previously fully documented cases of recurrence of the original disease after lung transplantation. We report a patient who underwent single-lung transplant in 1990 for end-stage respiratory failure secondary to biopsy-proved giant cell interstitial pneumonitis (GIP). There was no further industrial exposure. Surveillance bronchoscopies and biopsies post-transplant demonstrated eosinophils and giant cells in the bronchoalveolar lavage of both lungs, and in biopsies of the transplanted organ. Two years after successful transplantation the patient deteriorated and underwent open lung biopsy, which demonstrated not only bronchiolitis obliterans but also the classic features of GIP. There was no evidence of inorganic particles in the transplanted lung. Autopsy confirmed the presence of numerous giant cells characteristic of GIP with associated fibrosis throughout the transplanted lung. Although tungsten and other inorganic particles were again demonstrated in the native lung, there was no evidence of tungsten particles in the transplanted lungs. We believe that this case documents recurrence of the original disease after lung transplantation. The absence of unusual inorganic particles in the transplanted lung in the face of the classic picture of GIP is highly suggestive of an autoimmune mechanism for this occupation-associated disease. The appropriateness of transplant in the management of this lung disease should be reviewed further.

Adult↗
PubMed1993

Human placental 11 beta-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform.

Excess glucocorticoids impair fetal growth and cause teratogenesis. Placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the inactivation of cortisol to cortisone, preventing the high maternal cortisol levels from reaching the fetal circulation and thus preserving the low cortisol fetal environment. In previous work, an NADP-dependent isoform of 11 beta HSD has been purified from rat liver, a cDNA isolated, and the human homolog cloned. However, much evidence suggests tissue-specific 11 beta HSD activities that cannot be explained by the liver-type isoform. Therefore, we have partially purified human placental 11 beta HSD and compared it to the enzyme in rat liver. Human placental subcellular fractions exhibited NAD-dependent 11 beta HSD activity, but showed little activity with NADP. The enzyme had a pH optimum of 7-8.5 (peak, 7.7), was only sparingly soluble in detergents (solubility with Triton X-100 was very poor), and exhibited little latency or change in pH profile in detergent solution. By contrast, rat liver 11 beta HSD was exclusively NADP dependent and was easily solubilized by a wide range of detergents (including Triton X-100), revealing substantial latency and altered pH profile [optimum of 10, becoming 7-10 (peak, 9.5) in detergent]. These data do not merely reflect species differences, as rat placental 11 beta HSD was similar to the human placental isoform. AMP affinity chromatography, which was completely without affinity for rat liver 11 beta HSD, achieved a 1000-fold purification of human placental 11 beta HSD. This had Km values for corticosterone (mean +/- SE, 14 +/- 1 nM) and cortisol (approximately 55 nM) that were over 100 times lower than that for liver 11 beta HSD. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed identification of a band (apparent mol wt, 40,000) that correlated consistently with human placental 11 beta HSD activity (contrasting with a mol wt of 34,000 for rat liver 11 beta HSD). Thus, the NAD-dependent human placental 11 beta HSD is distinct from the previously characterized rat liver isoform and may be the product of a separate gene.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

Angiosarcoma arising from malignant schwannoma in a patient with neurofibromatosis.

A 20-year-old man with von Recklinghausen disease had a right neck mass. Pathologic examination at excision showed angiosarcoma arising in a malignant schwannoma of the cervical brachial plexus. Comparison with previous reports revealed that angiosarcoma is a rare, highly aggressive sarcomatous element in malignant schwannoma arising in patients with neurofibromatosis (NF).

Adolescent↗
PubMed1991

The influence of lower respiratory illness on childhood asthma: defining risk and susceptibility.

This article reviews the role of lower respiratory illness as a risk factor for the development of asthma in childhood. Lower respiratory illness may influence the natural course of lung-function growth and decline directly or indirectly promoting the development of asthma symptoms in susceptible individuals. The authors discuss the current definitions of lower respiratory illness and asthma and the characteristics of the individuals most prone to their effects. Last, they review how socioeconomic status and race affect the lower respiratory illness-asthma relationship.

Asthma↗