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Biomedical subjects

D Simmons

Publications and source records attributed to D Simmons.

At least 19 recordsLinked to original sources
PubMed1995

Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon.

Adhesion molecules are involved in facilitating cell-mediated immune events. Because lymphocyte-epithelial cell interaction has been implicated in the pathogenesis of colonic inflammation, we analysed expression of a range of adhesion molecules on colonic epithelium in vitro and in vivo using flow cytometry, immunohistochemistry and in situ hybridization. Expression of ICAM-1 by cell lines HT29 and int407 was increased by proinflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1 but not by IL-6. Vascular cell adhesion molecule (VCAM) and E-selectin were not expressed. Immunohistochemistry using sections of inflamed colon from 16 patients with ulcerative colitis (UC), five patients with Crohn's disease (CD) and seven patients with normal colonoscopic biopsies, showed no expression of ICAM-1 on colonic epithelium. VCAM was seen in isolated lymphoid aggregates and E-selectin was expressed on endothelium. In situ hybridization showed no ICAM-1 or ICAM-3 mRNA in colonic epithelium. B7, the ligand for CD28, was not found on normal or inflamed colonic epithelium. The adhesion molecules ICAM-1, ICAM-3 and B7 are not involved in lymphocyte-epithelial cell interaction in the normal or inflamed colon. This may have implications for the development of T cell tolerance to intestinal luminal antigens.

Antigen-Presenting Cells↗
PubMed1994

CD44H expression by human neuroblastoma cells: relation to MYCN amplification and lineage differentiation.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment, and tumor metastasis. Due to the alternative splicing of the single gene, a large family of different variants or isoforms is generated. Several reports have indicated an up-regulation of CD44 variant (v) isoforms in malignant process, conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor characterized by an aggressive and metastatic behavior in advanced stages with amplification of the MYCN protooncogene. In this report we show that the CD44 standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no expression of CD44 was detected on MYCN amplified stage IV tumors, thus demonstrating a highly significant negative relationship between MYCN amplification and CD44 expression in neuroblastoma. The expression of CD44 on neuroblastoma cultured cell lines was not shown to be related to MYCN amplification but rather linked to the S-type, schwann/glial differentiation lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6 antibodies and Northern blot analysis of mRNA from cell lines with probes spanning exons 4-10 did not reveal any expression of splice variants on neuroblastomas of all stages and cell lines, thus ruling out a major role of these isoforms in neuroblastoma progression and metastasis.

Blotting, Northern↗
PubMed1994

Carboplatin and granulocyte colony-stimulating factor as first-line treatment for epithelial ovarian cancer: a phase I dose-intensity escalation study.

A phase I study of frequently administered carboplatin with recombinant human granulocyte colony-stimulating factor (filgrastim) has been performed in patients with newly diagnosed epithelial ovarian cancer. Recombinant human granulocyte colony-stimulating factor was administered at a dose of 5 micrograms/kg/d for days 1 through 12 after carboplatin treatment. Carboplatin doses were calculated using a pharmacokinetic formula on an area under the curve (AUC) basis. Four doses of carboplatin were planned for each patient. The first cohort of patients received an AUC of 5 mg/mL x min every 3 weeks. Subsequently four additional cohorts received AUCs of 5, 7, 9, and 8 every 2 weeks. Non-hematologic toxicities were mild and not significant. The dose-limiting toxicity was thrombocytopenia and occurred at an AUC of 9. Most patients could complete treatment at an AUC of 7. Results for AUC 8 are awaited. Complete and partial responses were seen in most patients at all dose levels.

Adenocarcinoma↗
PubMed1992

Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide.

Two forms of cyclooxygenase are known to be present in eukaryotic organisms: a cyclooxygenase (COX-1) first purified from ram seminal vesicles encoded by a 2.8-kilobase mRNA, and a newly discovered mitogen-inducible cyclooxygenase (COX-2) encoded by a 4-kilobase mRNA. Expression of these two forms of the enzyme in rat alveolar macrophages stimulated with lipopolysaccharide was investigated by 1) determining the activity of newly synthesized enzyme after inactivating the endogenous enzyme with aspirin; 2) comparing levels of newly synthesized enzyme proteins in cells treated with or without lipopolysaccharide; and 3) assessing the expression of the mRNAs encoding COX-1 and COX-2. Levels of enzyme proteins were assessed by Western blot analysis and immunoprecipitation of 35S-labeled enzyme using two different antibodies, one specific for COX-2 and the other recognizing both forms of the enzyme but preferentially recognizing COX-1. We report here that the enhanced cyclooxygenase activity induced by the bacterial lipopolysaccharide in rat alveolar macrophages is caused by selective expression of the COX-2. Expression of COX-2 in macrophages stimulated by lipopolysaccharide was completely inhibited by dexamethasone, whereas COX-1 was unaffected. In resting unstimulated macrophages, only COX-1 but not COX-2 was detected. Levels of mRNA for the COX-2 in macrophages were increased, but those of the COX-1 were not affected by lipopolysaccharide as assessed by reverse transcription coupled with polymerase chain reaction. These results indicate that increased synthesis of prostaglandins and thromboxanes in lipopolysaccharide-stimulated macrophages results from selective expression of COX-2.

Animals↗
PubMed1992

Has the process causing noninsulin dependent diabetes start at birth? Evidence in neonates from a population with a high prevalence of diabetes.

AIMS: to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes. METHODS: fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers. RESULTS: the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies. CONCLUSIONS: the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation.

Adult↗
PubMed1992

Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen.

Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable degree of molecular mimicry to the extracellular matrix protein elastin. It contains both repetitive motifs PGVGV and VGVAPG. Immunofluorescence using a monoclonal antibody against VGVAPG confirmed that this peptide is expressed on sporozoites as predicted. The presence of VGVAPG is particularly interesting since this is the ligand for elastin receptors on a range of cell types, including macrophages/monocytes which are a major class of host target cells. It is proposed that this antigen represents the ligand whereby T. annulata recognises its host cells.

Amino Acid Sequence↗
PubMed1992

Gender issues and borderline personality disorder: why do females dominate the diagnosis?

There are significantly more females with the diagnosis of borderline personality disorder than males. This article explores the developmental factors that place females at a greater risk to develop the disorder. Societal expectations that increase the emerging of borderline symptoms are also discussed. Gender differences of "normal" behavior that effect the assigning of the diagnosis are explained. The theory that borderline personality disorder has become the "virus" of psychiatry is presented.

Adult↗
PubMed1992

A phase II trial of goserelin (Zoladex) in relapsed epithelial ovarian cancer.

Thirty patients with advanced epithelial ovarian cancer were treated with the luteinising hormone releasing agonist, goserelin. There were two partial responses lasting 40 and 105 weeks respectively. In addition five patients had disease stabilisation lasting 25, 35, 40, 66 and 70 weeks respectively and 23 patients had progressive disease. No significant or unexpected toxicities occurred. This minimally toxic therapy halted disease progression for 6 months or more in 23% of patients, the majority of whom were heavily pretreated. There were five early deaths due to disease progression. The use of goserelin in patients with epithelial ovarian cancers resistant to or relapsing soon after first line platinum based chemotherapy needs to be further evaluated.

Adult↗
PubMed1992

Prevalence of diabetes in different regional and religious south Asian communities in Coventry.

The prevalence of Type 2 (non-insulin-dependent) diabetes in different South Asian (Asian) communities was compared during the Coventry Diabetes Study, a cross-sectional house to house screening programme for diabetes. Screening was by capillary whole blood glucose measurement with oral glucose tolerance tests when concentrations were greater than or equal to 6.0 mmol l-1 within 2 h of a meal or greater than or equal to 5.0 mmol l-1 2 h or more after a meal and a random 10% of others. Of the 4395 resident Asians, 94% were represented by five communities: Punjabi Sikhs, Punjabi Hindus, Gujerati Moslems, Gujerati Hindus, and Pakistani Moslems. Response to screening was 77-89% and to glucose tolerance test was 59-79%. Differences in anthropometry, socioeconomic circumstances, and migratory patterns were found, but all groups had a higher prevalence of Type 2 diabetes than Europeans. Gujerati Moslems had the highest age-adjusted prevalence (per 1000) of Type 2 diabetes (males: 160 (95% CI 107-228), females: 204 (95% CI 144-283)) when compared with the other Asian groups (males: Punjabi Sikhs 89(72-110), Pakistani Moslems 91(67-120), Gujerati Hindus 84(57-120), Punjabi Hindu 113(74-171); females: Punjabi Sikhs 75(60-94), Pakistani Moslems 103(78-133), Gujerati Hindus 88(62-122), Punjabi Hindu 116(77-174)). That all the Asian groups had a high prevalence of diabetes, in spite of their known dietary, cultural, and socioeconomic differences, suggests that the Asian predisposition to Type 2 diabetes is inherited although environmental factors may be necessary for this to be expressed.

Adult↗
PubMed1992

Parity, ethnic group and the prevalence of type 2 diabetes: the Coventry Diabetes Study.

The prevalence of Type 2 (non-insulin-dependent diabetes) in relation to parity was compared among South Asian (Asian) and European women during a cross-sectional house-to-house screening programme for diabetes in Foleshill, Coventry, UK. The parity of female residents was ascertained in 8 of the 12 areas visited. These areas contained 2096 European (68 with diabetes diagnosed) and 1148 Asian women (95 with diabetes diagnosed). Crude prevalence of Type 2 diabetes was 3.2% and 14.7% in Europeans aged 30-64 years and > or = 65 years, respectively, and 10.9% and 36.5% in similarly aged Asians, respectively. In those aged 30-64 years, the age and body mass index adjusted prevalence of Type 2 diabetes was highest among nulliparous (Europeans 4.4%, Asians 16.3%) and grand multiparous (parity > or = 5: Europeans 6.3%, Asians 16.5%) women when compared with women who had had 1 or 2 deliveries (Europeans 0.9%, Asians 3.3%, p < 0.001, both ethnic groups). However, parity had no effect among women aged > or = 65 years.

Adult↗
PubMed1992

Diabetes self help facilitated by local diabetes research: the Coventry Asian Diabetes Support Group.

Diabetic South Asians know less about the nature of diabetes than Europeans. In view of the difficulties in communicating with diabetic South Asians in a clinical environment, a 'self help group' was established. The group was initially resourced by the Coventry Diabetes Study, became independent after 2 years and has met monthly for 4 years. Meetings are led and organized by local diabetic South Asians and include invited speakers and discussions. All meetings are held in one of the South Asian languages, particularly Punjabi. Attendance has ranged from 15 to 50, almost exclusively from the surveyed diabetic population of one electoral ward. Those with a high glycated haemoglobin (HbA1 > 9.5%) were assessed 12 months after invitation to the group, 44% (22/51) of whom attended at least twice. Those living over 1 mile from the meeting place and those speaking a minority language were least likely to attend. Those who attended the group had a greater drop in HbA1 and increase in 'knowledge score' than those not attending (both p < 0.01). The continued existence of the group illustrates the ability of local health workers to facilitate and empower local communities to become more responsible for their own health.

Adolescent↗
PubMed1992

Abnormal myoinositol influx in human leucocytes in diabetes but not specifically in diabetic neuropathy.

Abnormal myoinositol metabolism has been implicated as a contributor to the development of diabetic neuropathy. Furthermore, in vitro glucose inhibits animal and human myoinositol transporters. To investigate whether myoinositol transport is abnormal in diabetic subjects with and without neuropathy, we used a triple-isotope technique to measure [14C]myoinositol uptake in leucocytes from 23 insulin-dependent diabetic subjects and 13 matched nondiabetic subjects. All subjects with diabetes underwent neurophysiological studies, and subjects without neuropathy were compared with those with various degrees of neuropathy. The relationship between glycemia and flux was also studied. Diabetic subjects had similar intracellular and plasma myoinositol concentrations but had higher rates of uptake of myoinositol over the extracellular concentrations of myoinositol studied. Although the derived Km, Vmax, and passive components were not significantly different, the Vmax:Km ratio was significantly higher in diabetic subjects compared with nondiabetic subjects (0.25 [0.17-0.32] vs. 0.16 [0.13-0.19], respectively (P = 0.006). In diabetic subjects, the rate of myoinositol uptake correlated with HbA1c, particularly at 3 microM extracellular myoinositol where active uptake was a high proportion of the total influx (P less than 0.005). No difference in myoinositol uptake was found among diabetic subjects with various degrees of neuropathy. We conclude that although myoinositol transport is abnormal in diabetes, it is not specifically abnormal in diabetic neuropathy. Prolonged hyperglycemia is associated with higher myoinositol flux.

Biological Transport↗
PubMed1991

Serological response to measles revaccination in a highly immunized military dependent adolescent population.

In the spring of 1986, there was a measles outbreak in the city of El Paso, Texas, with 92 cases reported to the City-County Health Department. Of those 92 cases, 31 (32%) occurred within a public high school's student population of 2524. A mass measles vaccination program was undertaken at that high school in order to limit the outbreak. The student enrollment included a military dependent population of 368 students. Despite documented histories of prior measles immunizations in this military dependent subgroup, three individuals contracted the disease. Since this subgroup of students represented a highly immunized adolescent population, it was of interest to serologically determine their immune status prior to and following reimmunization with the expectation that such a study would provide information relating to the level of "protective" immunity. Prevaccination and postvaccination sera were obtained from 95 students. Results of measuring anti-measles antibody activity by ELISA indicate that 13 (14%) students responded to revaccination and experienced a fourfold or greater rise in IgG antibody levels. There were no detectable IgM responses. All of the students who responded to revaccination produced an anamnestic response (IgG boost only). Since most of these individuals had received first immunizations at 15 months of age or older, these findings suggest that secondary vaccine failure (waning immunity) was responsible for the putative "lowered" immunity in these individuals, instead of primary vaccine failure (maternal antibody suppression). These findings support current recommendations for measles booster revaccination of school-age children and adolescents.

Adolescent↗