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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 559 records · Page 31Linked to original sources
PubMed1996

Gas chromatographic determination and negative-ion chemical ionization mass spectrometric confirmation of 4,4'-methylenebis(2-chloroaniline) in urine via thin-layer chromatographic separation.

An analytical method for monitoring 4,4'-methylenebis(2-chloroaniline) (MOCA) in urine was developed. The MOCA extract from a urine sample was derivatized with pentafluoropropionic anhydride and subsequently cleaned-up via TLC before being analysed by a gas chromatograph equipped with an electron capture detector. Heptafluorobutyric anhydride derivatized MOCA was used as the internal standard during quantification. The method showed that the analytical interferences are effectively minimized by using the TLC technique for sample clean-up. Recoveries of spiked MOCA in urine at levels of 7.5, 22 and 62.5 micrograms dm-3 were all over 90% with the limit of detection determined to be 1 microgram dm-3. Confirmation of MOCA in a urine sample was performed by using a gas chromatograph mass spectrometer in negative-ion chemical ionization mode.

Chromatography, Thin Layer↗
PubMed1996

Subcutaneously administered recombinant human beta-interferon in the treatment of chronic hepatitis B virus infection.

BACKGROUND: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. beta-Interferon treatment has been less well studied than alpha-interferon. METHODS: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant beta-interferon (rINF-beta ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24-54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6 x 10(6) U/dose and the high-dose group received 30 x 10(6) U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. RESULTS: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-beta ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P = N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P = N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an antihepatitis B 'e' antigen at the end of 18 months. CONCLUSION: This study shows that subcutaneously administered rINF-beta ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.

Adult↗
PubMed1996

Rapid review.

Explore the source record for details and available documents.

Female↗
PubMed1996

Virus-like particles as a rotavirus subunit vaccine.

Rotavirus subunit vaccines are being evaluated for use in humans. The virus-like particles (VLPs) for these vaccines are produced in insect cells coinfected with combinations of baculovirus recombinants expressing bovine RIF VP2 and simian SA11, VP4, VP6, or VP7 rotavirus proteins. VLPs were administered parenterally to mice and rabbits, and the immunogenicity and protective efficacy of the vaccines were evaluated. Rabbits vaccinated with VP2/4/6/7 or VP2/6/7 VLP combinations developed high levels of rotavirus-specific serum antibody and fecal IgG but not fecal IgA. The induction of fecal IgG was associated with total or partial protection from oral challenge with ALA rotavirus. Heterotypic serum and fecal neutralizing antibody was induced in mice vaccinated parenterally with G1 VP2/6/7 or VP2/4/6n VLPs. VLPs were highly immunogenic when administered in QS21 adjuvant, inducing serum neutralizing antibody titers comparable to those induced by SA11 virus. VLPs are effective immunogens when administered parenterally and may be an effective subunit vaccine.

Animals↗
PubMed1996

Magnetic resonance imaging in alcoholic Korsakoff's syndrome: evidence for an association with alcoholic dementia.

A magnetic resonance imaging study of 19 alcoholic Korsakoff patients, 17 non-amnesic alcoholics and 23 non-alcoholic controls was undertaken. Several measures of ventricular size and interhemispheric area were significantly greater in the Korsakoff patients. Interhemispheric fissure size was greater in the non-amnesic alcoholics than the non-alcoholic controls. Cortical grey matter T1 values were essentially the same for the three groups, whereas the deep grey and the white matter T1 values for the Korsakoff patients were significantly greater than the non-alcoholic controls. These results indicate widespread cerebral atrophy in alcoholic Korsakoff patients, which is largely subcortical and does not develop independently of the diencephalic pathology. Alcoholic dementia may be a more severe form of alcoholic Korsakoff syndrome, aetiologically related to the nutritionally-induced diencephalic pathology, rather than the neurotoxic effects of alcohol on the cortex.

Adult↗
PubMed1996

Total antioxidant capacity of human seminal plasma.

Although the importance of seminal plasma in the protection of spermatozoa against reactive oxygen species is well known, only a few studies have investigated its antioxidative properties and the possible relationship between infertility and plasmatic antioxidant defences. The aim of the present study was to assess the status of the total non-enzymatic antioxidant defences of human seminal plasma. Semen samples were obtained from 101 patients consulting for infertility and 15 fertile donors. A total reactive antioxidant potential (TRAP) in seminal plasma was determined by luminol-chemiluminescence. The relationship of seminal TRAP values to lipid peroxidation was also evaluated. Our results show that semen samples from fertile controls show total antioxidant capacity at higher frequency and value than equivalent samples from suspected subfertile men. This fact as well as the inverse relationship observed between antioxidant capacity and lipid peroxidation potential strongly suggest that impaired antioxidant defences may play a role in infertile disorders.

Antioxidants↗
PubMed1996

Fibrodysplasia (myositis) ossificans progressiva: clinicopathological features and natural history.

Patients with fibrodysplasia (myositis) ossificans progressiva (FOP) (n = 28) were studied for up to 24 years. All had characteristic short big toes potentially recognizable at birth; there were radiographic changes in the toes, thumbs, cervical spine and metaphyses of the long bones, including exostoses. Ossification in the large skeletal muscles began from birth to 16 years (mean age 4.6 years) initially in 25 patients in the neck and upper spinal muscles, and later around the hips, major joints and jaw. The rate and extent of disability was unrelated to the time of onset. There was no evidence that any form of treatment produced consistent benefit. Despite the unique combination of skeletal abnormalities and ectopic ossification, the first diagnosis in patients with FOP was often wrong and usually delayed after ectopic ossification began (mean 2.7 years, range 0-14). Except where presentation was unusual, such as progressive stiffness, this delay was mainly due to failure to recognize the significance of the abnormal toes. The most frequent erroneous histological diagnoses were soft tissue sarcoma or fibromatosis. This series emphasizes the usually incorrect initial diagnosis, the misinterpretation of the histology, the unpredictable prognosis and the failure of current treatment. Despite its extreme rarity, there is a need for wider knowledge of this condition both to avoid clinical errors and to stimulate research.

Abnormalities, Multiple↗
PubMed1996

Trophoblast proliferation rate does not predict progression to persistent gestational trophoblastic disease in complete hydatidiform mole.

Persistent gestational trophoblastic disease (PGTD) is a significant complication of complete hydatidiform mole. There are, however, no reliable clinical or pathological parameters to predict the development of PGTD following the evacuation of a complete mole. In this study we examined the value of Ki67 expression in the prediction of PGTD following complete mole. Immunohistochemistry for Ki67 was performed on 21 cases of complete mole complicated by PGTD and 17 cases that resolved spontaneously after evacuation. Strong Ki67 expression was seen in both villous cytotrophoblast and extravillous trophoblast of the complete moles. The Ki67 index of extravillous trophoblast was significantly higher than that of villous cytotrophoblast. There was no significant difference in Ki67 index of either villous cytotrophoblast or extravillous trophoblast between cases of complete mole complicated by PGTD and those that resolved spontaneously. Trophoblast proliferation rate does not predict outcome following complete hydatidiform mole. Other factors involved in myometrial invasion may be of importance in the development of this complication, but serum chorionic gonadotrophin level is the only reliable predictor of the development of persistent gestational trophoblastic disease.

Biomarkers↗
PubMed1996

99Tcm-IMMU4 imaging in recurrent colorectal cancer: efficacy and impact on surgical management.

The aims of this study were to evaluate the efficacy of scintigraphy with the 99Tcm-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody Fab' fragment (IMMU4) in the diagnosis of recurrent colorectal carcinoma and to investigate its usefulness in the intraoperative surgical management of patients undergoing re-operation because of a rising serum CEA. We evaluated 24 patients prospectively who had rising serum CEA 6-19 months after initial surgery for colorectal carcinoma. Ten patients had lesions confirmed by computed tomography, ultrasound, magnetic resonance imaging, endoscopic examination or barium enema. Fourteen patients had negative findings on one or more of the above studies, but were suspected of having occult disease from their rising serum CEA. All patients were scheduled for surgery for restaging during a "second look' procedure. Planar and single photon emission tomography (SPET) imaging was performed in all patients. All scintigraphic findings were correlated with surgical and histopathological results. The overall sensitivity, specificity and accuracy were 81, 90 and 86% respectively when analysed by lesion, and 95, 60 and 88% respectively when analysed by patient. Ten of 14 (71%) patients with occult disease were correctly diagnosed as having recurrent disease. The SPET images were shown to have superior detectability (80%) compared with the planar images (35%). The surgeon judged the study to have had a neutral impact in 75% of the patients, but to have been helpful in 25%. We conclude that this antibody is potentially useful in detecting recurrent colorectal carcinoma in patients with rising serum CEA, especially when conventional imaging is negative or equivocal. It can also be helpful in altering planned surgery.

Adenocarcinoma↗
PubMed1996

Tissue reactions to biodegradable and non-degradable membranes placed transcutaneously in rats, observed longitudinally over a period of 4 weeks.

The aim of this study was to observe the tissue responses to a number of membrane materials processed for use in guided tissue regeneration at different time periods. Non-degradable Gore-Tex PTFE membrane and degradable polylactic acid (PLA) membranes were placed transcutaneously in surgical incisions made in the dorsum of rats. The tissue responses to these materials were observed histologically at 3 days, 1 week and 4 weeks after placement. A wide variation in the tissue responses to both materials was evident at each time period. These variations could not be attributed to different rates of healing over time, but rather to more complex factors. These factors may include differences in host responses between different animals, local factors pertaining to specific site variations, physical characteristics of the materials like surface texture, and contamination from the wound surface. Neither membrane material was found to be totally satisfactory. The PLA membranes were well tolerated by the tissues but they were unevenly absorbed within 2 weeks of placement. The Gore-Tex PTFE membranes, however, were associated with prolonged acute inflammatory infiltrate throughout the duration of the study, indicating that they were less well tolerated by the tissues than the PLA materials. As the healing characteristics of tissues are complex and highly variable, and as neither the non-degradable PTFE or degradable PLA membranes demonstrated ideal tissue responses, it is concluded that variations in clinical responses to these materials used in regeneration techniques must be anticipated.

Absorption↗
PubMed1996

Cyclic AMP-dependent anion secretion in human small and large intestine.

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.

Adolescent↗
PubMed1996

Social support as road map and vehicle: an analysis of data from focus group interviews with a group of African American women.

As part of a larger study of the impact of a social support intervention on pregnancy outcome for lower-income African American women, 6 African American women (a medical social worker, a physician's assistant, 2 community outreach workers, a lactation consultant, and a health project representative) participated in focus group discussions concerning the unique social support needs of lower-income African American women during pregnancy. Transcripts of focus group interviews were analyzed using qualitative content analysis. Emergent themes included strengths of African American communities, deficiencies in social support for many lower-income African American women, the meaning of pregnancy for African American women, the ability of many pregnant women to "make it" without visible means of support, young women's locations "inside" and "outside" of "mainstream" life, and the importance of social support as a mechanism for guiding and transporting "lost souls" back into the mainstream.

Black or African American↗
PubMed1996

Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence.

p16CDKN2 specifically binds to and inhibits the cyclin-dependent kinases CDK4 and CDK6, which function as regulators of cell cycle progression in G1 by contributing to the phosphorylation of the retinoblastoma protein (pRB). Human cell lines lacking functional pRB contain high levels of p16 RNA and protein, suggesting a negative feedback loop by which pRB might regulate p16 expression in late G1. By a combination of nuclear run-on assays and promoter analyses in human fibroblasts expressing a temperature-sensitive simian virus 40 T antigen, we show that p16 transcription is affected by the status of pRB and define a region in the p16 promoter that is required for this response. However, the effect is not sufficient to account for the differences in p16 RNA levels between pRB-positive and -negative cells. Moreover, p16 RNA is extremely stable, and the levels do not change appreciably during the cell cycle. Primary human fibroblasts express very low levels of p16, but the RNA and protein accumulate in late-passage, senescent cells. The apparent overexpression of p16 in pRB-negative cell lines is therefore caused by at least two factors: loss of repression by pRB and an increase in the number of population doublings.

Base Sequence↗
PubMed1996

Surface expression of the Chicxulub crater

Analyses of geomorphic, soil, and topographic data from the northern Yucatan Peninsula, Mexico, confirm that the buried Chicxulub impact crater has a distinct surface expression and that carbonate sedimentation throughout the Cenozoic has been influenced by the crater. Late Tertiary sedimentation was mostly restricted to the region within the buried crater, and a semicircular moat existed until at least Pliocene time. The topographic expression of the crater is a series of features concentric with the crater. The most prominent is an approximately 83-km-radius trough or moat containing sinkholes (the Cenote ring). Early Tertiary surfaces rise abruptly outside the moat and form a stepped topography with an outer trough and ridge crest at radii of approximately 103 and approximately 129 km, respectively. Two discontinuous troughs lie within the moat at radii of approximately 41 and approximately 62 km. The low ridge between the inner troughs corresponds to the buried peak ring. The moat corresponds to the outer edge of the crater floor demarcated by a major ring fault. The outer trough and the approximately 62-km-radius inner trough also mark buried ring faults. The ridge crest corresponds to the topographic rim of the crater as modified by postimpact processes. These interpretations support previous findings that the principal impact basin has a diameter of approximately 180 km, but concentric, low-relief slumping extends well beyond this diameter and the eroded crater rim may extend to a diameter of approximately 260 km.

Carbonates↗
PubMed1996

A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth.

The family of tissue inhibitors of metalloproteinases (TIMPs) presently numbers four distinct gene products that are specific inhibitors of the matrix metalloproteinases (MMPs). The local balance between MMPs and TIMPs is believed to play a major role in extracellular matrix (ECM) remodeling during development and in diseases such as cancer and arthritis. Unlike the other TIMPs, which are soluble. TIMP-3 is unique in being a component of ECM. Mutations in the human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus dystrophy or SFD). In this article, we summarize what is currently known about TIMP-3, discuss possible mechanisms leading up to SFD, and investigate the effect of TIMP-3 on tumor growth. Breast carcinoma and malignant melanoma cell lines were transfected with TIMP-3 expression plasmids and injected subcutaneously into nude mice. Growth curves of the resulting tumors over a period of 6 to 8 weeks demonstrated that increased expression of TIMP-3 resulted in a statistically significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding ECM by tumor cells may inhibit tumor growth by preventing local expansion of tumor, retarding the release of growth factors sequestered in ECM, or inhibiting angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, we believe that the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action.

Animals↗