Complex co-localization of chromogranins and neurohormones in the human gastrointestinal tract

Co-localization of chromogranin (Cg) A, B, and C has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal tract (corpus, antrum, duodenum, ileum, and colon) using single-, double-, and triple-immunofluorescence stainings. Virtually all enterochromaffin (EC) cells contained CgA, and those in the luminal two thirds of the antral mucosa and villi of small intestine often also contained CgB. A few EC cells in the duodenal crypts contained CgC. Most gastrin cells harbored both CgB and CgA, although rather more CgB than CgA, but some gastrin cells contained all three types, i.e., also CgC. Some CCK cells also contained all three chromogranins. Enteroglucagon cells in the duodenal villi contained CgA and some CgB. CgA (but not B or C) was found in some secretin, GIP, enteroglucagon/peptide YY, and neurotensin cells. A few somatostatin cells contained CgA but neither CgB nor CgC. CgA and C were found mainly in the basal cell region, whereas CgB occurred more diffusely throughout the cytoplasm. This varying distribution suggests that not all secretory granules contain CgA, or that CgB may occur in a nongranular form. The varying composition of the different chromogranins may reflect their complex functional roles in the widespread neuroendocrine system.     

Alloantigen-stimulated anti-HIV activity

A number of studies have suggested that an immune response to human leukocyte antigen (HLA) alloantigens may contribute to protection against HIV infection. In the present study, we examined the effect of alloantigen-stimulated cell lines obtained from peripheral blood mononuclear cells (PBMC) of HIV-uninfected (HIV-) individuals and the soluble factors produced by these cell lines on HIV-1 replication. Multiple in vitro restimulation with irradiated allogeneic PBMC from HIV- donors resulted in the expansion of CD8(+) T-cell lines that inhibited HIV-1 replication when cocultured with either autologous or heterologous in vitro-infected phytohemagglutinin (PHA) blasts. Supernatants from the alloantigen-stimulated cell lines also inhibited HIV replication in both PHA blasts and a chronically infected cell line. The alloantigen-stimulated cell lines and the factors they produced inhibited both T-cell-tropic (T) and macrophage-tropic (M) isolates of HIV-1. Blocking experiments using anti-chemokine antibodies suggested that this inhibition of HIV replication was not due to the beta-chemokines present in cocultures of cell lines with HIV-infected blasts. These results indicate that alloantigen-stimulation of PBMC from HIV- individuals activates CD8(+) T cells that produce soluble factor(s) that inhibit HIV replication of a wide spectrum of HIV-1 isolates through a chemokine-independent mechanism. This is a US government work. There are no restrictions on its use.     

Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer

Fine-needle aspiration cytology (FNAC) is the most useful procedure for the evaluation of thyroid nodules. The requirement for repeated aspirations in the follow-up of benign nodular thyroid disease, however, is controversial. To determine the value of re-aspirations in benign nodular thyroid disease, we studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19 male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151) thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46 were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407 (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change after multiple aspirations in 213 (98.61%) of the cases. Three patients with initial aspirations read as benign had a diagnosis of PC from their second biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC revealed atypical features in 1 of the 3 patients. These 3 patients likely represent a false-negative result of the initial FNAC rather than benign nodular disease transformed to a malignant one during the follow-up period. In conclusion, a second aspiration of clinically suspicious nodules may correct a few initial false-negative results, but routine additional re-aspirations are not useful for clinically stable disease.     

Peripheral benzodiazepine receptor expression on leukocytes and neutrophil function during anticonvulsant monotherapy

AIM: To gain a full understanding of the concept of equity and means of promoting and monitoring a more equitable healthservice. BACKGROUND: With previous policy decisions having sidelined equity, a new government is likely to wish to reverse this trend. ORIGINS OF INFORMATION: Government and expert opinion. DATA ANALYSIS: A critical approach to previous literature. KEY ISSUES: Equity is not a unitary concept and so it is explored and dissected using the framework of: Distribution of Resources, Access and Uptake of Healthcare, Standards and Outcomes of Healthcare, Health Status. Means of improving and monitoring equity in these four areas are suggested. CONCLUSIONS: There are a number of ways of considering the concept of equity and for any fruitful discussion to occur there needs to be an agreed working definition. Specific topics are discussed where equity is lacking and a plan of action is suggested which is likely to improve equity in the areas identified.     

Variations of the frontal exit of the supraorbital nerve: an anatomic study

Meningeal worm (Parelaphostrongylus tenuis) is a neurotropic nematode of ungulates in eastern North America. Lack of an effective diagnostic test increases the concern of translocating potentially infected ungulates into western North America, where P. tenuis does not occur naturally. In an attempt to identify serodiagnostic molecules, we determined (1) whether elk (Cervus elaphus) experimentally infected with P. tenuis produce antibodies against infective larvae or adult worms, and (2) if sera consistently recognize antigens that distinguish P. tenuis from a common nematode parasite of elk, the lungworm Dictyocaulus viviparus. Each of 10 elk were exposed to 15 or 300 infective P. tenuis larvae. Serum was collected (0, 41, and 83 days post-exposure and at necropsy) and monitored for antibodies using the enzyme-linked immunosorbent assay (ELISA) and immunoblot. When reactivity of sera with larval P. tenuis protein was compared (day 0 versus 83), ELISA values were significantly higher on day 83 for elk exposed to 15 or 300 parasites. Likewise, ELISA values using protein of adult P. tenuis were higher for elk exposed to 300 larvae. Immunoblots showed that sera from elk, with adult worms in the central nervous system, consistently recognized the 25-27, 28-30, and 34-36 kDa antigens of infective larvae after 83 days. However, many D. viviparus molecules were found to cross-react with antibodies formed against meningeal worm antigens. Use of adult worm proteins for serodiagnosis appears limited, because no protein was consistently recognized by sera collected from elk exposed to 15 larvae. We believe that development of a reliable diagnostic test for meningeal worm requires more research addressing cross-reactivity and detection of P. tenuis during the incubation stage.     

Daily subcutaneous injection of low-dose interleukin 2 expands natural killer cells in vivo without significant toxicity

We aimed to determine the toxicity and immunological effects of daily s.c. administered low-dose interleukin (IL) 2. Adult cancer patients received a single daily s.c. injection of IL-2 as outpatients for 90 consecutive days. Cohorts of four to nine patients were treated at escalating IL-2 dose levels until the maximum tolerated dose (MTD) was defined. Peripheral blood mononuclear cell phenotyping, IL-2 serum levels, and the presence of anti-IL-2 antibodies were investigated. Thirty-eight patients were treated at seven IL-2 dose levels ranging from 0.4 to 1.75 million International Units (mIU)/m2 daily. The MTD was 1.25 mIU/m2, with constitutional side effects, vomiting, and hyperglycemia dose limiting. Severe toxicity did not occur at or below the MTD, although mild local skin reaction and mild constitutional side effects were common. Objective tumor regressions were not observed during this Phase I trial. Low-dose IL-2 resulted in natural killer (NK) cell (CD3(-) CD56(+)) expansion at all dose levels. This effect was dose dependent (P < 0.01), ranging from a 154 to 530% increase over baseline. Peak NK levels were achieved at 6-8 weeks and sustained through 12 weeks of therapy. As predicted by in vitro studies of IL-2 receptor structure-activity relationships, the subset of NK cells that constitutively express high-affinity IL-2 receptors (CD3(-)CD56(bright+)) showed more profound dose-dependent expansion, with increases ranging from 368 to 2763% (P = 0.015). NK expansion occurred at peak IL-2 levels <10 pM (2.3 IU/ml). Three patients developed nonneutralizing anti-IL-2 antibodies. Thus, we concluded that selective expansion of NK cells may be achieved in vivo with daily s.c. injections of low-dose IL-2 with minimal toxicity.     

Patients' experiences of patient-controlled analgesia

We examined patients' experiences of patient-controlled analgesia by the use of semistructured interviews in 26 patients shortly after discontinuation of the device. The options expressed by the patients were examined qualitatively to identify recurring themes in their experience of patient-controlled analgesia. The areas of interest were analgesia, factors influencing whether the patient pressed the button or not, whether they felt in control and side effects. Negative as well as the expected positive evaluations were found. The negative evaluations reflected problems with nausea and vomiting and inadequate analgesia. No clear strategy for pressing, or not pressing, the button emerged and the principle of control by the patient over their pain relief was not considered important.