Effect of pindolol on the prolactin response tod-denfluramine

We studied the effect of the 5-HT_1A receptor antagonist, pindolol, on the prolactin (PRL) response to the 5-HT releasing agent,d-fenfluramine (d-FEN), in ten healthy male volunteers. Pindolol pretreatment lowered baseline PRL levels but, when this effect was taken into account, did not significantly attenuate the PRL response tod-FEN. Within the limitations that attend the use of pindolol as a 5-HT_1A receptor antagonist, the data suggest that although 5-HT_1A receptors may play a role in the tonic release of PRL, they are not involved in the release of PRL produced byd-FEN. We propose that the PRL response tod-FEN may involve selective activation of postsynaptic 5-HT₂ receptors.     

Avoidance therapy in reactive dye-induced occupational asthma: long-term follow-up.

BACKGROUND: Previous studies reported that early diagnosis and avoidance therapy are the most important factors for prevention of permanent lung impairment; however, few studies have evaluated the long-term prognosis of reactive dye-induced occupational asthma (RD-OA). OBJECTIVE: To evaluate the long-term outcomes of RD-OA. METHODS: Methacholine airway hyperresponsiveness (AHR) and lung functions were evaluated and compared in 26 patients with RD-OA at the time of diagnosis and after complete avoidance of the causative agents. Patients with continued (n = 13) or remitted (n = 6) AHR were further monitored for up to a mean +/- SD of 8.7 +/- 1.8 years. RESULTS: The AHR resolved in 10 (38%) of 26 patients a mean +/- SD of 2.2 +/- 1.3 years after complete avoidance of RDs; however, prebronchodilator forced expiratory volume in 1 second (FEV1) values were not different. Levels of IgE specific to the RD-human serum albumin complex were markedly decreased at first follow-up in 5 RD-atopic patients from whom paired serum samples were compared (P = .02). The AHR disappeared in an additional 5 patients and improved in 4 by the second follow-up. The FEV1 values also improved compared with diagnosis and first follow-up levels. Favorable prognosis was associated with early diagnosis of RD-OA and complete avoidance of the causative agent. No association was found with smoking history, latent periods, the presence of RD specific IgE, baseline provocation concentration that caused a decrease in FEV1 of 20%, or FEV1. CONCLUSIONS: Early diagnosis and avoidance therapy are the most important prognostic factors in RD-OA. The AHR and lung function of patients with RD-OA can sometimes be recovered steadily and slowly through avoidance measures.     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

New Latex Bead Agglutination Assay for Differential Diagnosis of Cattle Infected with Mycobacterium bovis and Mycobacterium avium subsp. paratuberculosis

Extensive studies have shown that the current assays used to identify cattle infected with Mycobacterium bovis or Mycobacterium avium subsp. paratuberculosis are not sufficiently sensitive and specific to detect all infected animals, especially animals recently infected with the pathogens. In the present report we show that these limitations might be overcome with a latex bead agglutination assay (LBAA). With the specific immunodominant epitope (ESAT6-p) of M. bovis, we developed an LBAA and enzyme immunoassay (EIA) for that purpose and compared them with the “gold standard” culture method and skin test for their efficacy in detecting bovine tuberculosis. When sera from control healthy cows (n = 10), M. avium subsp. paratuberculosis-positive cattle (naturally infected, n = 16; experimentally infected, n = 8), and M. bovis-positive cattle (naturally infected, n = 49;experimentally infected, n = 20) were applied to an EIA and an LBAA developed with ESAT6-p, the two tests showed similar sensitivity (97.1% by EIA, 95.7% by LBAA), high specificity (94.2% by EIA, 100% by LBAA), and a positive correlation (kappa value, 0.85; correlation rate, 93.2%; correlation coefficient, 0.64). Receiver operating characteristic analysis of EIA results and comparison with the culture method determined a suitable cutoff value at 0.469, with an area under the curve of 0.991 (95% confidence interval, 0.977 to 1.0). As LBAA didn't show any positive reactions with sera from uninfected control cows or M. avium subsp. paratuberculosis-infected cattle, which were confirmed to be free of M. bovis by culture or PCR, LBAA using the ESAT6-p can be a rapid and useful M. bovis diagnostic assay. The data suggest that rapid, sensitive, and specific assays can be developed with peptides containing immunodominant epitopes present in proteins uniquely expressed in M. bovis or M. avium subsp. paratuberculosis for differential diagnosis of cattle infected with M. bovis or M. avium subsp. paratuberculosis.     

Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor

Cross-linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand-induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell-specific proteins in mediating these interactions. For this, we expressed mIgM in the non-hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface-expressed IgM to interact with the cytoskeletal matrix upon cross-linking with anti-μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell-specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton-binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin-based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM-cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand-induced mIgM binding to the cytoskeletal matrix.     

Intracranial metastasis from clear cell sarcoma of the kidney--a case report.

Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease.     

Effect of suramin on differentiation of human stomach cancer cell lines.

This study was designed to demonstrate that differentiation of stomach cancer cells can be modified by microenvironmental change and to look for a method inducing or promoting tumor cell differentiation. To evaluate the biomorphological characterization of tumor cell differentiation in suramin-containing in vitro culture of human stomach cancer cell lines, inverted phase-contrast microscopic examination, analysis of growth curves and BrdU-positive S-phase fraction, immunocytochemical study, radioimmunoassay for CEA, transmission electron microscopic examination, DNA flow cytometry, and heterotransplantation in SCID mice were performed. Suramin inhibited tumor cell growth. Development of intracytoplasmic lumina and intercellular lumina was noted in suramin-containing culture with formation of numerous microvilli and frequent desmosomes. The amount of CEA released by a cell was increased in suramin-containing culture. Suramin inhibited heterotransplantation, and a transplant from suramin-containing culture revealed a much higher degree of differentiation than that from suramin-absent culture. Suramin induced no change in DNA ploidy pattern. Elimination of suramin from the culture medium did not reverse the tumor cell differentiation. Each stomach cancer cell line showed a different degree of responsiveness to suramin. In conclusion, this study shows that suramin inhibits growth of SNU-5 and SNU-16 cells and that suramin induces differentiation of SNU-16 cells.