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Biomedical subjects

S Law

Publications and source records attributed to S Law.

At least 73 records · Page 4Linked to original sources
PubMed1997

The roles of multimodality treatment and lymphadenectomy in the management of esophageal cancer.

PURPOSE: To review the current status of multimodality treatment and lymphadenectomy in the management of esophageal cancer. DATA SOURCES: Literature review. STUDY SELECTION: Multimodality treatment and lymphadenectomy in esophageal cancer. DATA EXTRACTION: Results in research papers published selected by literature search. RESULTS: Numerous studies have been carried out attempting to define the roles of various neoadjuvant or adjuvant regimens in the treatment of esophageal cancer. These included the use of radiotherapy or chemotherapy alone or in different combinations, with or without surgical resection. Randomized trials have failed to show significant improvement compared with surgical resection alone, although downstaging of disease and benefits on subgroups of patients could be demonstrated. Whether the extent of resection can influence outcome was tested by varying the surgical approach, and by increasing the extent of lymphadenectomy. Although indirect evidence exists suggesting more extensive resection may improve long term prognosis, definitive proof is lacking. CONCLUSIONS: More well organized randomized controlled trials are needed to further elucidate the roles of these approaches in the treatment of esophageal cancer.

Combined Modality Therapy↗
PubMed1995

Interaction of somatostatin receptors with G proteins and cellular effector systems.

Somatostatin induces its multiple biological actions by interacting with a family of receptors, referred to as sstr1-sstr5. To determine the molecular mechanisms of action of somatostatin, we have investigated the interaction of the different cloned receptors with G proteins and cellular effector systems. sstr2, sstr3 and sstr5 associate with pertussis toxin-sensitive G proteins and are able to mediate the inhibition of adenylyl cyclase activity by somatostatin. Two forms of sstr2, sstr2A and sstr2B, are generated by alternative splicing and differ in their C-terminal amino acid sequence. sstr2B couples to adenylyl cyclase whereas sstr2A does not. To investigate the basis for the differential coupling to adenylyl cyclase, we truncated sstr2B to the point of amino acid sequence divergence from sstr2A. The truncated sstr2B mediated the inhibition of cAMP formation by somatostatin, indicating that the C-terminus is not needed for coupling sstr2 to adenylyl cyclase. It is likely that the C-terminus of sstr2A hinders coupling to adenylyl cyclase. sstr2A associates with Gi alpha 3 and G(o) alpha but does not effectively interact with Gi alpha 1, a G protein that is necessary for coupling somatostatin receptors to adenylyl cyclase. The differential association of the splice variants with Gi alpha 1 may explain their contrasting effects on adenylyl cyclase activity. sstr3 also couples to adenylyl cyclase. Gi alpha 1 links sstr3 to adenylyl cyclase and mutagenesis studies have shown that the C-terminus of Gi alpha 1 is necessary for this coupling. The C-terminus of the Gi alpha proteins differ by only a few amino acid residues and only Gi alpha 1 couples sstr3 to adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Regional variation in content, composition and organization of porcine epithelial barrier lipids revealed by thin-layer chromatography and transmission electron microscopy.

Epidermis and oral epithelia provide permeability barriers that limit penetration of potentially harmful agents. Barrier function is determined by lipids in the superficial epithelial layers and varies regionally by more than 10-fold. The purpose of this study was to determine whether differences in lipid content, composition or organization could account for this variation in barrier function. Stratum corneum from skin, gingiva and palate and superficial layers from buccal regions and the floor of the mouth were isolated, and lipids were extracted and analysed by thin-layer chromatography. Tissue from each region was examined by electron microscopy. There was an inverse correlation between permeability and ceramide content and a direct correlation with triglyceride content. Electron microscopy revealed that the intercellular space in epidermal stratum corneum contained multiple lipid lamellae displaying an alternating broad-narrow-broad spacing. In palatal and gingival stratum corneum, uniformly spaced lamellae were present at the periphery of dilations of the intercellular space, but the interiors of the dilations contained disorganized lamellae and electron-dense material. In the non-keratinized barriers, there was a single, broad lamella at the cell periphery and occasional short stacks of lamellae traversing the intercellular space. These intercellular lamellae may be derived from a population of membrane-coating granules that contain internal lamellae. The results suggest that ceramides may be important barrier components, even in non-keratinizing epithelia where they are very minor components. Regional differences in the physical organization of barrier lipids may also contribute to differences in barrier function.

Animals↗
PubMed1995

Positive and negative neuropsychiatric features in Alzheimer's disease.

Positive neuropsychiatric features (paranoia, delusions, hallucinations) and negative features (disinterest/withdrawal, apathy, reduced speech output, reduced physical activity) occur in Alzheimer's disease (AD), although most studies have focused on positive features alone. Positive features may be associated with a more severe and rapidly progressive subtype of AD. A retrospective analysis of prospectively obtained research data (101 probable AD patients) revealed that patients with positive features had been ill longer but were otherwise similar to patients with negative features. Patients with any neuropsychiatric features had more rapid progression and more severe cognitive and comprehension deficits than patients without such features. Neuropsychiatric features in AD likely reflect variations in mesocortical and mesolimbic degeneration rather than an etiologic or prognostic subtype.

Aged↗
PubMed1995

Validation of a French version of an informant-based questionnaire as a screening test for Alzheimer's disease.

BACKGROUND: Development of informant-based screening tests for dementia is an emerging field. The reliability and validity of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), an instrument that screens for dementia in general, have been established. We conducted a study to validate a French version of the IQCODE as a screening test for Alzheimer's dementia in the elderly living in the community. METHOD: In the Canadian Study of Health and Aging, subjects were screened in their own homes using the modified Mini-Mental State Exam (3-MS). Those who screened positive, along with a sample of subjects who screened negative, were referred for a complete clinical examination. In Quebec, an informant was asked to complete the French version, IQCODE(F), at that time. Based on the final clinical diagnoses, performances of the IQCODE(F) and Mini-Mental State Examination (MMSE, converted from 3-MS) in screening for Alzheimer's disease were evaluated. RESULTS: Of the 237 subjects, the mean IQCODE (F) score was 3.4 (s.d. = 0.6), on a 5-point scale (1 = improvement in condition over the past 10 years, 5 = marked deterioration, 3 = no change). The mean MMSE score was 23.1 (s.d. = 4.5). The scores on the two scales were correlated (r = -0.44, P < 0.001). The IQCODE(F) scores were unrelated to education (r = -0.07, P > 0.3) in contrast to the MMSE scores (r = 0.28, P < 0.001). With respect to a diagnosis of probable Alzheimer's disease, the IQCODE(F) (cut-off point 3.6) had a sensitivity of 75% and a specificity of 95.6%. The sensitivity and specificity of the MMSE (cut-off point 23) were 70% and 82.3% respectively. CONCLUSION: The findings of the IQCODE(F) are consistent with those of the English version in correlation with the MMSE and apparent freedom from educational bias. The IQCODE is superior to the MMSE as a screening test for probable Alzheimer's disease in the elderly living in the community. It may be a useful addition to the screening tests already available, especially for the less well educated.

Aged↗
PubMed1994

Case report: lymphangiomyomatosis with spontaneous peritoneal rupture.

Radiological appearances of pulmonary and retroperitoneal lymphangiomyomatosis in a 47-year-old Chinese woman are described. Onset of abdominal symptoms and development of ascites heralded spontaneous rupture of retroperitoneal lymphangiomyomatosis, which is illustrated on computed tomography.

Ascites↗
PubMed1993

A comparison of transhiatal and transthoracic resection for oesophageal carcinoma.

We compared the results of 327 transthoracic (TT) resections and 82 transhiatal (TH) resections for carcinoma of the oesophagus operated on between July 1982 and June 1991. Significantly more patients with carcinoma of the lower third of the oesophagus (54% versus 28%) and with increased pulmonary risks for surgery (61% versus 22%) were selected for the TH approach as compared with the TT approach. Results showed comparable intraoperative complications between the two groups. 5% of patients in the TH group required a thoracotomy for control of haemorrhage (3 patients) and repair of bronchial tear (1 patient) which occurred during the transmediastinal dissection. Postoperatively, mechanical ventilation requirement and complications involving the cardio-pulmonary systems were similar between the two groups. Anastomotic leakage occurred in 3% and 4%, respectively for the TH and TT patients (p = NS), whereas hoarseness occurred in 16% and 5%, respectively (p = 0.001). The 30-day mortality rates and hospital mortality rates were comparable between the two groups as were the overall survival rates. Our results suggested that while TH resection did not diminish the operative morbidity and mortality rates overall, it is appropriate for patients with increased pulmonary risks to be preferentially selected for this approach, and for tumours located in the upper and lower portion of the thoracic oesophagus where dissection of the tumour can be carried out mostly under vision.

Aged↗
PubMed1992

Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.

Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.

Animals↗
PubMed1992

Chronic naltrexone treatment of rats: effects on gastrointestinal opioid peptide content.

The gastrointestinal tract contains immunoreactive enkephalins and beta-endorphin. The objective of the current study was to determine whether chronic treatment of rats with naltrexone altered the gastrointestinal tissue content of these opioid peptides. Opioid activity measured by radioreceptor assay was detectable throughout the gastrointestinal tract. There were regional differences in the [Met5]enkephalin: [Leu5]enkephalin-immunoreactivity (IR) ratios, possibly due to cell specific differential processing of precursor molecules or degradation of the peptides. Chronic naltrexone treatment increased opioid activity in the duodenum and jejunum, decreased [Met5]enkephalin-IR in the duodenum and [Leu5]enkephalin-IR in the gastric corpus, and increased beta-endorphin-IR in the duodenum. However, the changes were small, and it is unlikely that any functional changes resulting from naltrexone treatment can be reliably ascribed to such changes in tissue content.

Animals↗
PubMed1992

Regulation of hepatic growth hormone receptors in coho salmon (Oncorhynchus kisutch).

Factors potentially regulating hepatic growth hormone (GH) receptors in coho salmon (Oncorhynchus kisutch) have been investigated. From December to June of the first year, relative changes in hepatic 125I-sGH binding and 35SO4 incorporation by ceratobranchial cartilage were similar. Stunted salmon, which in seawater have elevated plasma GH yet fail to grow, showed lower hepatic 125I-sGH binding than did normally growing seawater salmon. However, MgCl2 treatment of stunts' membranes to reveal total specific binding of 125I-sGH indicated receptor occupation by endogenous sGH. Total specific 125I-sGH binding was low in seawater stunts and remained low if these fish remained unfed after return to fresh water, but increased approximately twofold upon feeding. Total specific binding in fasted salmon in fresh water showed a trend toward decreased levels by 1 week; by 3 weeks, binding was 40% lower than in fed fish. There was a positive correlation (r = 0.600) between condition factor and total specific binding in fed and fasted salmon in fresh water. Two weeks after hypophysectomy total specific binding was 50% lower than in sham-operated control salmon, indicating pituitary regulation of GH receptors. GH treatment reduced both free and total 125I-sGH binding in salmon examined 24 hr after treatment. Treatment with recombinant bovine insulin-like growth factor I, thyroxine, or cortisol did not affect free 125I-sGH binding. Both the pituitary and nutrition appear to be prime regulators of hepatic GH receptors in coho salmon.

Analysis of Variance↗
PubMed1989

Prediction of persistent immunodeficiency in the DiGeorge anomaly.

To assess the natural history of the immune defect in DiGeorge anomaly, we reviewed serial immunologic studies in 18 patients. The diagnosis was made with criteria based on the concept of the DiGeorge anomaly as a field defect. Initial or early follow-up laboratory examination suggested moderate to normal T cell function in 14 patients. None of these patients have lost T cell capability; they have never had infections characteristic of T cell deficiency. Four patients had clinical and laboratory evidence of profound immunodeficiency. A decreased number of CD4+ cells (less than 400/microliters) and a decrease in phytohemagglutinin responsiveness (stimulation index less than 10) may be useful in discriminating patients with immunodeficiency; absolute lymphocyte count and immunoglobulin values were not informative. At the time of surgery, the thymus was not found in 11 of 14 patients; however, only two of these patients had immunodeficiency. Patients with a persistently low number of CD4+ cells and decreased phytohemagglutinin response are candidates for immunologic reconstitution.

Aging↗
PubMed1987

Intermediate filaments cytokeratin and vimentin in ovarian sex cord-stromal tumours with correlative studies in adult and fetal ovaries.

The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.

Adult↗
PubMed1986

Expression of low molecular weight cytokeratin proteins in cervical neoplasia.

CAM 5.2 is a monoclonal antibody which identifies lower molecular weight cytokeratin proteins (50, 43 and 38 kD). It is an antibody which works reliably on formalin-fixed, paraffin-embedded tissues. In this study, using CAM 5.2 in the indirect immunoperoxidase method we have examined ectocervical epithelium ranging from normal, through metaplasia and cervical intraepithelial neoplasia to invasive squamous carcinoma. CAM 5.2 is demonstrated to be a useful indicator of changes associated with malignant transformation in the ectocervix.

Antibodies, Monoclonal↗
PubMed1986

Hypotension-induced hypokalaemia in sheep.

Plasma K+ was measured in Merino ewes during 50-90 min periods of hypotension induced by sodium nitroprusside, isoprenaline, verapamil or nifedipine. Doses were adjusted to produce falls in systemic blood pressure of approximately 20 mmHg. All of these drugs caused decreases in plasma K+ which could not be attributed to increased urinary excretion of K+. In all cases plasma renin activity increased during the hypotension. Plasma aldosterone concentration which was measured in some sodium nitroprusside experiments also increased during the hypotension. However, enhancement of the plasma renin activity and plasma aldosterone concentration responses by prior sodium depletion of the sheep by furosemide administration or suppression of the plasma renin activity and plasma aldosterone concentration responses by prior salt loading did not influence the magnitude of the hypotension-induced hypokalaemia.

Adrenergic beta-Agonists↗