Gastrointestinal upsets and new copper plumbing--is there a connection?

This article summarizes two investigations that examine the health effects of prolonged exposure to copper-contaminated drinking water. The first study was initiated after elevated copper levels were detected in several homes that were either newly constructed or recently remodeled. All of these homes were served by the same municipal water supplier.

Proliferation marker Ki-S5 as a diagnostic tool in melanocytic lesions.

Background: A discrimination between benign and malignant melanocytic lesions is not always possible by conventional histology.

Objective: Our purpose was to determine the proliferative activity in various types of melanocytic neoplasms and to appraise its value as a diagnostic adjunct.

Methods: The growth fraction was assessed immunohistochemically in 398 melanocytic lesions by means of the monoclonal antibody Ki-S5 directed to the Ki-67 antigen.

Immunophenotyping of dermal spindle cell tumors: diagnostic value of monocyte marker Ki-M1p and histogenetic considerations.

Various studies have reported the utility of anti-CD34 staining in the differential diagnosis of dermal spindle-cell tumors. To investigate whether monoclonal antibody Ki-M1p might add practical diagnostic information, we examined a total of 120 cutaneous spindle cell neoplasms using a panel of markers. Anti-CD34 antibody QBEnd/10 consistently stained dermatofibrosarcomas, Kaposi's sarcomas, neurofibromas, and, to a lesser extent, hemangiopericytomas.

Immunizing preschool children: beliefs and practices of pediatric residents.

Immunization practices and knowledge of vaccine contraindications among pediatric residents were assessed at five pediatric training facilities by surveying 227 pediatric residents. Residents administer vaccines even in the presence of an afebrile minor illness. They are less likely to vaccinate if a fever (< 102 degrees F) is present.

Insulin stimulates mitogen-activated protein kinase by a Ras-independent pathway in 3T3-L1 adipocytes.

To characterize tissue-specific differences in insulin signaling, we compared the mechanisms of mitogen-activated protein (MAP) kinase activation by insulin in the mitogenically active 3T3-L1 fibroblasts with the metabolically active 3T3-L1 adipocytes. In both cell lines, insulin significantly increased p21(ras).GTP loading (1.

Role of mitochondria in tributyltin-induced interleukin-1alpha production in murine keratinocytes.

Tributyltin (TBT) salts are well known skin irritants in rodents and humans. TBT induced both the intracellular production of interleukin-1alpha (IL-1alpha) and its release into culture medium in a murine keratinocyte cell line (HEL30). Here, we report that mitochondria are important for TBT-induced IL-1alpha production.

Estimation of ozone with total ozone portable spectroradiometer instruments. II. Practical operation and comparisons.

We used a microcomputer-controlled total ozone portable spectroradiometer instrument #21 (MTOPS21) to measure solar radiation at 298, 304 and 310 nm in Greenbelt, Md., during 1995. One day's ozone measurements from a Brewer instrument (B105) were used to calibrate the 304- and 310-nm channel ratios to a theoretical model.

The antiovulatory activity of progesterone antagonists is not correlated to their antiprogestational potency in the rat.

Progesterone antagonists often differ in regard to their potency to block ovulation in rats although they may possess similar 'antiprogestational' (abortive) activity. Therefore, the questions arose as to: (a) whether antiovulatory and antiprogestational effects (on endometrial and mammary gland parameters) of antiprogestins correlate at all; and (b) which mechanism(s) may be responsible for their ability to abolish ovulation. To answer these questions we set out to compare the influences of two progesterone antagonists, Onapristone (ON) a very potent and ZK 136798 only a weak inhibitor of ovulation, to assess changes on the one hand on typical progestational actions and on the other hand on factors known to regulate ovulation.

Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance.

Inhibition of protein kinase C (PKC) is discussed as a new approach for overcoming multidrug resistance (MDR) in cancer chemotherapy. For evaluation of this concept we applied the bisindolylmaleimide GF 109203X, which shows a highly selective inhibition of PKC isozymes alpha, beta 1, beta 2, gamma, delta and epsilon in vitro. The efficacy of this compound in modulation of MDR was examined using several P-glycoprotein (P-gp)-overexpressing cell lines including a MDR1-transfected HeLa clone, and was compared with the activities of dexniguldipine-HCI (DNIG) and dexverapamil-HC1 (DVER), both of which essentially act via binding to P-gp.

The PIE-1 protein and germline specification in C. elegans embryos.

Totipotent germline blastomeres in Caenorhabditis elegans contain, but do not respond to, factors that promote somatic differentiation in other embryonic cells. Mutations in the maternal gene pie-1 result in the germline blastomeres adopting somatic cell fates. Here we show that pie-1 encodes a nuclear protein, PIE-1, that is localized to the germline blastomeres throughout early development.

Interactions of protein kinase C with insulin signaling. Influence on GAP and Sos activities.

In this study, we investigated the influence of the protein kinase C (PKC)-dependent system upon the ability of insulin to stimulate p21(ras).GTP loading in 3T3-L1 adipocytes. Activation of PKC by 12-0-tetradecanoylphorbol-13-acetate (TPA) did not affect the basal amount of p21(ras).

Physician beliefs and knowledge about vaccinations. Are Cincinnati doctors giving their best shot?

The purpose of this study was to examine the immunization beliefs and practices of physicians in our community. A two-page descriptive survey of immunization practices and knowledge of vaccine contraindications was sent to all community physicians on the staff of Children's Hospital Medical Center in Cincinnati, Ohio. More than 90% of practitioners used well-child visits for immunization, even if the child was ill.

Cellular signalling as a target in cancer chemotherapy. Phospholipid analogues as inhibitors of mitogenic signal transduction.

Mitogenic signalling mechanisms emerged as novel targets for tumor chemotherapy. Current strategies for pharmacological interventions are briefly discussed. Phospholipid analogues are treated in greater detail.

Diagnostic assessment of two novel proliferation-specific antigens in benign and malignant melanocytic lesions.

The aim of this study was to gain a thorough insight into the proliferative activity of benign and malignant melanocytic tumors. A total of 314 cases were examined by immunohistochemistry on paraffin-embedded material. The growth fraction was assessed by means of two monoclonal antibodies, Ki-S1 and Ki-S5, which react with two different proliferation-specific nuclear antigens.

The prevalence of sexually transmitted diseases in children and adolescents evaluated for sexual abuse in Cincinnati: rationale for limited STD testing in prepubertal girls.

Objective: To determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, syphilis, and human immunodeficiency virus (HIV) infection in sexually abused children and to develop selective criteria for sexually transmitted disease (STD) testing in these children in our community.

Design: Prospective.

Setting: University-affiliated children's hospital in Ohio.

Interference of new alkylphospholipid analogues with mitogenic signal transduction.

The interference of several new hexadecylphosphocholine analogues with mitogenic signal transduction was investigated in NIH3T3 fibroblasts by studying the effects of these agents on thrombin-induced inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) formation and the subsequent Ca2+ release, on protein kinase C (PKC) in cell-free extracts, on the PKC-mediated activation of the Na+/H+ antiporter and on c-fos induction. The compounds investigated include hexadecylphosphocholine (HePC), octadecyl-[2-(N-methyl-piperidinio)-ethyl]-phosphate (D20133), octadecyl-(N,N-dimethyl-piperidinio-4-yl)-phosphate (D21266); octadecyl-[2-(trimethyl-arsonio)-ethyl]-phosphate (D21805) and hexadecylphospho-L-serine (HePS). The data indicate that (i) all compounds inhibit the thrombin-induced progression of growth-arrested NIH3T3 cells into S phase with similar IC50 values; (ii) the common denominator of all compounds is a reduction of Ins(1,4,5)P3 formation, resulting in an attenuation of Ca2+ release; (iii) the direct interaction with PKC does not significantly contribute to the antitumor activity of these agents; (iv) the new HePC congeners D21266, D21133 and D21805 affect the same targets as HePC, i.

Disturbance of follicular development and endocrine reactions induced by the antiovulatory effective progesterone antagonist Onapristone.

The present study was undertaken to investigate whether inhibition of ovulation, which is known to occur after treatment with progesterone antagonists, is due to the effect of high levels of prolactin. Therefore, rats with 4-day cycles were treated with the antiprogestin, Onapristone (ON), once daily starting on the evening of estrus. It was detected that the profile of peripheral prolactin levels during the treatment with ON was not remarkably different from that found in the controls.

Neopterin derivatives together with cyclic guanosine monophosphate induce c-fos gene expression.

We have previously shown that neopterin enhances hydrogen peroxide and chloramine T activity in a luminol-dependent chemiluminescence assay and strengthens toxicity of these agents against bacteria at slightly alkaline pH (pH 7.5), while 7,8-dihydroneopterin was shown to be a scavenger independent of the pH value. Besides various oxidants, phenolic antioxidants were shown to specifically induce expression of the c-fos and c-jun mRNAs.

[Multiple melanoma in xeroderma pigmentosum].

Xeroderma pigmentosum comprises a heterogeneous group of autosomal recessive hereditary diseases, which are characterized by a number of clinical characteristics and an abnormal DNA repair mechanism. Patients affected show a high frequency of mucocutaneous malignant tumors, especially squamous cell carcinomas and basal cell carcinomas. We report on a 65-year-old patient who successively developed a total of 15 malignant melanomas, 1 squamous cell carcinoma and 1 lymph node metastasis of a malignant melanoma.

The last deglaciation event in the eastern central arctic ocean.

Oxygen isotope records of cores from the central Arctic Ocean yield evidence for a major influx of meltwater at the beginning of the last deglaciation 15.7 thousand years ago (16,650 calendar years B.C.

The protein kinase C inhibitor ilmofosine (BM 41 440) arrests cells in G2 phase and suppresses CDC2 kinase activation through a mechanism different from that of DNA damaging agents.

The thioether phospholipid derivative ilmofosine (BM41440), a selective inhibitor of protein kinase C, is a new anticancer drug presently undergoing Phase II clinical trials. We have examined the influence of the compound on cell cycle progression. Ilmofosine was found to induce a dose-dependent accumulation of CA46 cells in G2-phase of the cell cycle.

[Presence of alternatively spliced messenger RNA for HLA-A, -B and -C in platelets].

Recently we demonstrated that platelets contain specific messenger RNA (mRNA) encoding for the transmembrane HLA class I molecule (44 kDa). In this study we analyzed lymphocytes as well as platelets for the presence of alternatively spliced mRNA with deleted transmembrane domain resulting in soluble HLA class I antigens (39 kDa). PCR amplification of lymphocyte RNA led to a product specific for alternatively spliced cDNA corresponding to the presence of soluble HLA in plasma, while this product could not be obtained from platelet mRNA.