PubMed Health⌕ Search

Biomedical subjects

J Slavin

Publications and source records attributed to J Slavin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nondigestible oligosaccharides.

Dietary carbohydrates range in molecular size from simple sugars to complex polymers with a degree of polymerization (DP) of up to 100,000 or more. Oligosaccharides are generally defined as carbohydrates from 2 to 20 monomeric units long. Oligosaccharides have been dietary staples since antiquity but have received much less attention than other carbohydrates such as simple sugars or dietary fiber. Recently, interest in oligosaccharides has increased not only because of properties that include sweetening ability and fat replacement, but also because of resistance to digestion in the upper gastrointestinal tract and fermentation in the large bowel. Thus, some oligosaccharides have functional effects similar to soluble dietary fiber such as enhancement of a healthy gastrointestinal tract, improvement of glucose control, and modulation of the metabolism of triglycerides. These oligosaccharides are the nondigestible oligosaccharides. These compounds are easily incorporated into processed foods and hold much promise as functional ingredients in nutraceutical products.

Chronic Disease↗
PubMed2000

Carbohydrates, dietary fiber, and incident type 2 diabetes in older women.

BACKGROUND: Dietary carbohydrates may influence the development of type 2 (non-insulin-dependent) diabetes, for example, through effects on blood glucose and insulin concentrations. OBJECTIVE: We examined the relations of baseline intake of carbohydrates, dietary fiber, dietary magnesium, and carbohydrate-rich foods and the glycemic index with incidence of diabetes. DESIGN: This was a prospective cohort study of 35988 older Iowa women initially free of diabetes. During 6 y of follow-up, 1141 incident cases of diabetes were reported. RESULTS: Total grain, whole-grain, total dietary fiber, cereal fiber, and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables. Multivariate-adjusted relative risks of diabetes were 1.0, 0.99, 0.98, 0.92, and 0.79 (P for trend: 0.0089) across quintiles of whole-grain intake; 1.0, 1.09, 1.00, 0.94, and 0.78 (P for trend: 0.005) across quintiles of total dietary fiber intake; and 1.0, 0.81, 0.82, 0.81, and 0.67 (P for trend: 0.0003) across quintiles of dietary magnesium intake. Intakes of total carbohydrates, refined grains, fruit and vegetables, and soluble fiber and the glycemic index were unrelated to diabetes risk. CONCLUSION: These data support a protective role for grains (particularly whole grains), cereal fiber, and dietary magnesium in the development of diabetes in older women.

Aged↗
PubMed2000

Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury.

BACKGROUND: Lung injury manifest clinically as adult respiratory distress syndrome (ARDS) is a common cause of morbidity and mortality following acute pancreatitis (AP). Neutrophils play a critical role in the progression of AP to ARDS. C-x-C chemokines are potent neutrophil chemoattractants and activators and have been implicated in AP. AIMS: To evaluate the effect of blocking the C-x-C chemokine, cytokine induced neutrophil chemoattractant (CINC), in AP on pancreatic inflammation and the associated lung injury in rats. METHODS: AP was induced by hourly intraperitoneal injections of caerulein. Goat anti-CINC antibody was administered either before or after starting caerulein injections to evaluate the prophylactic and therapeutic effects, respectively. Severity of AP was determined by measuring plasma amylase, pancreatic water content, and pancreatic myeloperoxidase (MPO) activity as a measure of neutrophil sequestration in the pancreas. Lung injury was determined by measurement of pulmonary microvascular permeability and lung MPO activity. RESULTS: Treatment with anti-CINC antibody had little effect on caerulein induced pancreatic damage. However, it reduced the caerulein mediated increase in lung MPO activity as well as lung microvascular permeability when administered either prophylactically (lung MPO (fold increase over control): 1.53 (0.21) v. 3.30 (0.46), p<0.05; microvascular permeability (L/P%): 0.42 (0.07) v. 0.77 (0.11), p<0.05) or therapeutically (lung MPO (fold increase over control): 2.13 (0.10) v 4.42 (0.65), p<0.05; microvascular permeability (L/P%): 0.31 (0.05) v 0.79 (0.13), p<0.05). CONCLUSION: Treatment with anti-CINC antibody afforded significant protection against pancreatitis associated lung injury. These results suggest that CINC plays an important role in the systemic inflammatory response in AP.

Acute Disease↗
PubMed2000

Pitfalls in the diagnosis of prostate adenocarcinoma from holmium resection of the prostate.

PURPOSE: Holmium laser resection of the prostate (HoLRP) provides tissue for histologic analysis that was not possible using previous coagulative laser prostatectomies. It was assumed that these tissue specimens would yield the same histologic information as specimens obtained by transurethal resection of the prostate and would be adequate for diagnosis of cancer. However, tissue subjected to laser treatment may sustain thermal injury, resulting in artifactual change. The aim of this study was to define the histologic characteristics of prostate tissue after holmium laser prostatectomy and the influence of thermal change on diagnosis of malignancy. MATERIALS AND METHODS: All prostate tissue was examined after HoLRP. Examination included prostate-specific antigen (PSA) staining and immunostaining for high-molecular-weight cytokeratins. Histologic features are described. RESULTS: Thermal injury after HoLRP was more extensive than previously believed. Artifacts observed under low power consisted of glandular distortion and contraction with crowding. Higher magnification revealed clumping of the chromatin of the nucleus, resulting in hyperchromasia and irregularity of the nucleus and loss of polarity. These changes may be mistaken for malignant change. It will be difficult to detect malignancy in areas involved by thermal injury. When prostate cancer exists, grading of cancer will be affected by these artifacts. Uptake of immunohistochemical staining with PSA and high-molecular-weight cytokeratins is nonspecific in areas of injury, reducing their usefulness in these cases. CONCLUSIONS: Detection of malignancy may be compromised by thermal injury occurring after HoLRP. Preliminary preoperative transrectal ultrasound-guided biopsies may still be necessary for diagnosis of malignancy.

Adenocarcinoma↗
PubMed1999

A novel orthotopic model of breast cancer metastasis to bone.

Breast cancer affects approximately one woman in twelve and kills more women than any other cancer. If detected early, patients have a five year survival rate of 66%, but once metastatic disease has developed, there is no effective treatment. About 70% of patients with metastatic disease have bone involvement, while lungs and liver are the other common targets. Bone metastases cause severe pain, pathological fractures and hypercalcaemia and thus are a significant clinical problem. The development of new therapies for metastatic breast carcinoma depends on a better understanding of the mechanism of homing of the tumour cells to bone, liver and lungs and the factors required for their growth in these organs. Research on mechanisms of breast cancer metastasis, particularly to bone, has relied on in vitro studies or on tumour models in which the inoculation route is designed to promote delivery of tumour cells to a specific organ. Metastases in bone are achieved by inoculation into the right ventricle of the heart. To our knowledge there has been no report of a model of metastatic spread from the mammary gland to distant sites which reliably includes bone. In this paper, we describe our recent development of a novel murine model of metastatic breast carcinoma. The new model is unique in that the pattern of metastatic spread closely resembles that observed in human breast cancer. In particular, these murine breast tumours metastasise to bone from the primary breast site and cause hypercalcaemia, characteristics not normally found in murine tumours, but common in human disease. Furthermore, in a preliminary characterisation of this model, we show that secretion of parathyroid hormone-related protein, a role for which has been implicated in breast cancer spread to bone, correlates with metastasis to bone. This model therefore provides an excellent experimental system in which to investigate the factors that control metastatic spread of breast cancer to specific sites, particularly bone. The special advantage of this system is that it involves the whole metastasis process, beginning from the primary site. Existing models consider mechanisms that pertain to growth of tumour once the site has been reached. An understanding of the regulation of these factors by potential therapeutic agents could lead to improvement in therapies designed to combat metastatic disease. For the first time, this development will allow exploration of the molecular basis of site-specific metastasis of breast cancer to bone in a clinically relevant model.

Animals↗
PubMed1999

Cytokines and acute pancreatitis.

Cytokines have been shown to play a pivotal role in multiple organ dysfunction, a major cause of death in severe acute pancreatitis. Moreover, the two-hit hypothesis of the cytokine-induced systemic inflammatory response syndrome explains the variable individual response to severe acute pancreatitis and the impact of secondary events such as sepsis or therapeutic intervention. Many experimental anti-cytokine therapies have been administered following induction of experimental pancreatitis, and have proved to be therapeutic. Patients with severe pancreatitis present early because of pain. Clearly then a window for therapeutic intervention is available between onset of symptoms and peak pro-inflammatory cytokine expression. It is this fundamental observation that convinces many in the field that the treatment of AP will be one of the first clinical successes for novel drugs or therapy that seek to modulate the inflammatory response.

Acute Disease↗
PubMed1999

Standard Kausch-Whipple pancreatoduodenectomy.

Despite the increasing number of clinical trials in pancreatic cancer there are no widely accepted definitions of different types of resection for pancreatic cancer. An agreed definition of the standard Kausch-Whipple pancreatoduodenectomy was derived by a group of international experts at a meeting in Castelfranco Veneto, Italy, in May 1998. The lymph node groups to be removed en bloc with the pancreatoduodenectomy and described using the Japanese Pancreas Society classification were as follows: 13a and 13b; 17a and 17b; 12b1, 12b2 and 12c; and 14a and 14b. Limited segmental major venous resection and adjacent organ resection, if required, may be included as part of a standard pancreatoduodenectomy. The pylorus-preserving procedure also may be included as part of standard resection, but not for tumours of the anterior-superior part of the head of the pancreas. Wider adoption of the definition of standard Kausch-Whipple resection will enable a more objective comparative analysis of the radicality of resection between institutions and permit a more coherant analysis on the type of surgery undertaken in multicentre adjuvant studies.

Combined Modality Therapy↗
PubMed1999

Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer.

Bone sialoprotein (BSP) and osteopontin (OPN) are secreted glycoproteins with a conserved Arg-Gly-Asp (RGD) integrin-binding motif and are expressed predominantly in bone. The RGD tripeptide is commonly present in extracellular attachment proteins and has been shown to mediate the attachment of osteosarcoma cells and osteoclasts. To determine the origin and incidence of BSP and OPN mRNA expression in primary tumor, a cohort of archival, primary invasive breast carcinoma specimens was analyzed. BSP transcripts were detected in 65% and OPN transcripts in 77% of breast cancers examined. In general, BSP and OPN transcripts were detected in both invasive and in situ carcinoma components. The transcripts were not detected in surrounding stromal cells or in peritumoral macrophages. Despite its abundance in carcinomas, BSP expression was not detected in a panel of 11 human breast cancer cell lines (MCF-7, T47D, SK-Br-3, MDA-MB-453, MDA-MB-231, MDA-MB-436, BT549, MCF-7ADR, Hs578T, MDA-MB-435, and LCC15-MB) and OPN expression was detected only in two of these (MDA-MB-435 and LCC15-MB). To examine the possibility that expression of these genes was down-regulated in cell culture, several cell lines were grown as nude mouse xenografts in vivo; however, these tumors also failed to express BSP. OPN expression was identified in all cell lines grown as nude mouse xenografts. Our data suggest that in human primary breast tumors, the origin of BSP and OPN mRNA is predominantly the breast cancer cells and that expression of these transcripts is influenced by the tumor environment.

Animals↗
PubMed1999

The future of surgery for pancreatic cancer.

Carcinoma of the pancreas has a grim prognosis even following surgical resection. Only a relatively small proportion of patients have a resectable tumour at presentation. At the present time it is uncertain whether the use of radical forms of surgery, or adjuvant therapy improve survival. It is however unlikely that either of these approaches will greatly increase the number of long term survivors. Earlier diagnosis particularly in individuals who are at greater risk of developing carcinoma of the pancreas is one way in which results might be improved. Unfortunately current imaging techniques are inadequate for the diagnosis of early disease. New molecular diagnostics techniques that can identify example mutations in oncogenes such as K-ras or deletions of tumour suppressor genes such as P53 or P16 are being developed. These tumour specific abnormalities are also a target for gene therapy. Surgery alone cannot cure any patient with pancreatic cancer but may in the future in conjunction with these new approaches.

Genetic Therapy↗
PubMed1998

Whole-grain intake and cancer: an expanded review and meta-analysis.

Whole grains are nutrient rich and may protect against chronic disease. To study this, we previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found consistently lower risk in those with high than in those with low whole-grain intake. Questions remained concerning other cancers, dietary assessment, quantity consumed, confounding, and differential study quality. Here we expand the review to 40 case-control studies of 20 cancers and colon polyps. Odds ratios are < 1 for 46 of 51 mentions of whole-grain intake and for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low intake. The pooled odds ratio for high vs. low whole-grain intake among the 45 mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to 0.78 across four types of dietary questionnaires. Odds ratios were < 1 in 9 of 10 mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone-related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8 other cancers. Most pooled odds ratios for specific cancers were in the range of 0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled odds ratio was similar in studies that adjusted for few and many covariates. Dose-response associations were stronger in studies using food-frequency questionnaires than in more quantitative questionnaires. The case-control evidence is supportive of the hypothesis that whole-grain intake protects against various cancers.

Adult↗
PubMed1998

Induction of a multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein.

Myelin oligodendrocyte glycoprotein (MOG) is postulated to be a target autoantigen in multiple sclerosis (MS). Here we investigated the encephalitogenicity of an immunodominant epitope of MOG, peptide 35-55, in various strains of mice. An MS-like disease was induced in NOD/Lt mice (H-2g7) and C57BL/6 mice (H-2b) by a single injection of MOG35-55 in CFA. The disease followed a relapsing-remitting course in NOD/Lt mice, whereas C57BL/6 mice developed a chronic paralytic disease. Histologically, the disease in both strains was characterized by cellular infiltration and multifocal demyelination in the CNS. Significant DTH type reactions to MOG35-55 were only seen in MOG-susceptible animals, with the NOD/Lt mice showing the strongest responses. Susceptible mice also showed specific antibody responses to MOG35-55 but not to a panel of other MOG peptides. These results provide further evidence for the role of MOG as a highly autoantigenic molecule capable of inducing severe demyelinating disease.

Animals↗
PubMed1998

Parathyroid-hormone-related protein in sarcoidosis.

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

Adult↗
PubMed1998

Endoscopic sphincterotomy for acute pancreatitis: arguments in favour.

Pathogenetic factors of acute biliary pancreatitis include persistent or transient, absolute or relative, obstruction of Vater's ampulla or the main pancreatic duct and reflux of bile into the pancreatic ducts or of pancreatic juice into the bile ducts. There is an increasing incidence of persisting common bile duct stones in the more severe forms of acute biliary pancreatitis, in patients who die, and in patients with pancreatic necrosis. All these findings provide a rational basis for the use of early biliary decompression in patients with acute biliary pancreatitis. Endoscopic sphincterotomy offers a cost-effective and safe alternative to surgical biliary decompression with an overall morbidity rate of 8% and mortality rate of 2.4%. Randomized clinical trials showed that endoscopic sphincterotomy is useful in patients with predicted severe attack of acute biliary pancreatitis and is clearly indicated in all patients who are jaundiced or who have associated cholangitis. In addition, the procedure is valid in preventing recurrent attack of acute biliary pancreatitis in high risk elderly patients with gallstones, unfit for any kind of cholecystectomy.

Acute Disease↗
PubMed1997

Whole-grain consumption and chronic disease: protective mechanisms.

Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable.

Acute Disease↗
PubMed1996

A primary intraosseous carcinoma of the anterior maxilla. Report of a new case.

The case of a primary intraosseous carcinoma occurring in the maxilla is presented. The classification; clinical, radiologic, and light microscopic features; and treatment are described. These rare lesions should be considered among the diagnostic possibilities when patients present with atypical cysts of the jaws.

Diagnosis, Differential↗
PubMed1996

The quantitation of metabolites of quercetin flavonols in human urine.

The flavonoid quercetin, or its metabolites, inhibit chemical carcinogenesis in rodents and may have a role in the prevention of human cancers. Quercetin exposure in human populations results from the dietary intake of various plant foods; high concentrations of quercetin are found in apples, onions, tea, and red wine. Determination of the relationship between dietary intake and cancer risk depends on the characterization of quercetin intake. The development and use of biomarkers for quercetin intake may provide a basis for the objective classification of this exposure. One possible biomarker is metabolic products of quercetin. We report the development of a high-performance liquid chromatography (HPLC)-based assay for quantitation of quercetin metabolites in human urine. The metabolites include 3,4-dihydroxyphenylacetic acid (homoprotocatechuic acid), metahydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid). The assay has only two major steps, ether extraction and HPLC analysis, and is suitable for analysis of large sample numbers. Analytical characteristics of the assay include a sensitivity of less than 1 microgram, precision with coefficients of variation < 10%, and metabolite recoveries > 90%. The mean concentrations of 3,4-dihydroxyphenylacetic acid, metahydroxyphenylacetic acid, and homovanillic acid in two human urine samples are approximately 0.7, 4.8, and 2.8 micrograms/ml, respectively. The identification of each metabolite is confirmed by HPLC, UV absorbance scans, and gas chromatography-mass spectrometry analysis. These results verify the occurrence of quercetin metabolites in human urine and the feasibility of quercetin metabolite quantitation, by the assay described herein, for epidemiological studies. Development of the analytical procedure is an essential first step for validation of the metabolites as biomarkers of quercetin intake.

3,4-Dihydroxyphenylacetic Acid↗