Outbreak of Listeria monocytogenes infections linked to a pasteurized ice cream product served to hospitalized patients.

Two cases of hospital-acquired listeriosis were linked to a commercially produced, pasteurized ice cream mix. Manufacturers should implement safety measures from the Food Safety Modernization Act to minimize the risk of Listeria contamination. Dietary guidelines for persons at high risk of listeriosis may need revision to recognize the potential risk from pasteurized products.

Toxicological evaluation of brominated vegetable oil in Sprague Dawley rats.

Brominated vegetable oil (BVO) has been approved by the US Food and Drug Administration on an interim basis as a food additive. Past studies have raised concerns about potential toxicities from consuming BVO. To investigate further these toxicities, we conducted a 90-day dietary exposure study in Sprague Dawley rats and analyzed tissue distribution of the main metabolites. Six-week-old male and female rats were fed diets containing 0 (control), 0.002%, 0.02%, 0.1%, or 0.5% BVO by weight. Statistically significant increases were observed in the serum bromide in the high-dose group of both sexes and in the incidence of thyroid follicular cell hypertrophy in the two highest dose groups of males and the high-dose group of females. An increase in serum TSH was observed in the high-dose group for both sexes, as well as a decrease in serum T4 in the high-dose males. A clear dose-response was observed in di- and tetra-bromostearic acid levels in the heart, liver, and inguinal fat. These data expand upon previous observations in rats and pigs that oral exposure to BVO is associated with increased tissue levels of inorganic and organic bromine, and that the thyroid is a potential target organ of toxicity.

Abnormalities of in vitro lymphocyte responses during rubella virus infections.

In vitro rubella virus infections of lymphocytes from normal adult humans impaired their responsiveness to phytohemagglutinin (PHA) stimulations; a situation which seemed analogous to the PHA unresponsiveness of peripheral lymphocytes from babies with the congenital rubella syndrome. Such in vitro viral infection of normal cells also decreased the synthesis of normal nucleic acids and structural proteins, and abrogated the enhanced DNA synthesis induced by pokeweed and specific antigen stimulations. Furthermore, it was shown that live rubella virus, but not ultraviolet-irradiated virus, was necessary for the impaired mitogenic responses of normal leukocytes. These observations are interpreted to favor the view that the virus achieves its inhibitory effect on the action of mitogens by interference either directly or indirectly at an intracellular site. Such an action could reduce the functional potential of lymphocytes and impair their effectiveness as immunologically competent cells or as effectors in immunologic reactions.

Induction of arthritis in monkeys by immunization with type II collagen.

Immunization of two cynomolugus and three rhesus monkeys with purified type II collagen resulted in the development of polyarthritis. Arthritis first became clinically apparent 7 wk after primary immunization and persisted for 16 mo. Radiologic examination of the limbs demonstrated soft tissue swelling with severe joint destruction including loss of cartilage and bone. Involved joints eventually became ankylosed with permanent loss of some motion. All of the monkeys developed a response to the immunizing collagen as determined by ELISA of serum for antibodies. Arthritis was associated with weight loss and constitutional symptoms, including lethargy and refusal to eat. One monkey became so debilitated that it was necessary to euthanize it. Histologic examination of the joints showed synovial hypertrophy with pannus formation. A control monkey immunized with type I collagen suffered no apparent ill effects.

Characterization of maturation-dependent extrinsic proteins of the rat sperm surface.

Mammalian spermatozoa must mature in the epididymis before they can fertilize an egg. It is known that modification of the protein composition of the sperm surface is an important part of the maturation process. In this paper, we present data on two related glycoproteins that can be extracted from mature but not immature spermatozoa. Cell surface radioiodination has shown that these proteins are on the sperm surface, and immunofluorescence microscopy, by use of monospecific antibodies to the proteins, has indicated that their localization is restricted to the periacrosomal region of the sperm head. We have also shown that in vitro, these proteins will bind to the identical region of immature sperm. Immunohistochemical localization of the proteins in the epididymis shows that they are produced and secreted by the cauda region. The significance of the addition of these proteins to the sperm surface in both maturation and fertilization is discussed.

Arrangement of tubulin subunits and microtubule-associated proteins in the central-pair microtubule apparatus of squid (Loligo pealei) sperm flagella.

This study provides a comprehensive, high-resolution structural analysis of the central-pair microtubule apparatus of sperm flagella. It describes the arrangement of several microtubule-associated "sheath" components and suggests, contrary to previous thinking, that microtubules are structurally asymmetric. The two microtubules of the central pair are different in several respects: the C2 tubule bears a single row of 18-nm-long sheath projections with an axial periodicity of 16 nm, whereas the C1 tubule possesses rows of 9-nm globular sheath components with an axial repeat of 32 nm. The lumen of the C2 tubule always appears completely filled with electron-dense material; that of the C1 tubule is frequently hollow. The C2 tubule also possesses a series of beaded chains arranged around the microtubule; the beaded chains are composed of globular subunits 7.5-10 nm in diameter and appear to function in the pairing of the C1 and C2 tubules. These findings indicate: that the beaded chains are not helical, but assume the form of lock washers arranged with a 16-nm axial periodicity on the microtubule; and that the lattice of tubulin dimers in the C2 tubule is not helically symmetric, but that there are seams between certain pairs of protofilaments. Proposed lattice models predict that, because of these seams, central pair and perhaps all singlet microtubules may contain a ribbon of 2-5 protofilaments that are resistant to solubilization; these models are supported by the results of the accompanying paper (R. W. Linck, and G. L. Langevin. 1981. J. Cell Biol. 89: 323-337.

First principles determination of the effects of phosphorus and boron on iron grain boundary cohesion.

Toward an electronic level understanding of intergranular embrittlement and its control in steels, the effects of phosphorus and boron impurities on the energy and electronic properties of both an iron grain boundary and its corresponding intergranular fracture surface are investigated by the local density full potential augmented plane wave method. When structural relaxations are taken into account, the calculated energy difference of phosphorus in the two environments is consistent with its measured embrittlement potency. In contrast to the nonhybridized interaction of iron and phosphorus, iron-boron hybridization permits covalent bonding normal to the boundary contributing to cohesion enhancement. Insights into bonding behavior offer the potential for new directions in alloy composition for improvement of grain boundary-sensitive properties.

Ingested mineral fibers: elimination in human urine.

Sediment in human urine examined by transmission electron microscopy contains amphibole fibers which originate from the ingestion of drinking water contaminated with these mineral fibers. The ingestion of filtered water results in the eventual disappearance of amphibole fibers from urine. These observations provide the first direct evidence for the passage of mineral fibers through the human gastro-intestinal mucosa under normal conditions of the alimentary canal.

Tonic immobility produces hyperalgesia and antagonizes morphine analgesia.

Hyperalgesia was demonstrated during and immediately after termination of tonic immobility in the lizard Anolis carolinensis. Additionally, tonic immobility antagonized morphine-induced analgesia. In conjunction with other research, these data suggest that the response is accompanied by a reduced availability of serotonin, possibly at postsynaptic receptors of raphe neurons.

Effect of amantadine hydrochloride on the response of human lymphocytes to phytohemagglutinin.

Amantadine hydrochloride (Symmetrel), which is an antiviral agent marketed for the prevention of infection by influenza virus, inhibits the mitogenic response of human lymphocytes stimulated with phytohemagglutinin. The concentrations which effectively inhibited the response to phytohemagglutinin were similar to those which maximally inhibit virus replication. The drug inhibited the mitogenic response without affecting the ability of phytohemagglutinin to agglutinate leukocytes. The data suggest that phytohemagglutinin, amantadine, and certain lipid-containing RNA viruses take part in cell-membrane interactions of common nature.

Viral inhibition of lymphocyte response to phytohemagglutinin.

The response to phytohemagglutinin by lymphocytes from eight of fourteen patients with congenital rubella was inhibited, whereas that of lymphocytes from patients with other diseases was not. The response of normal lymphocytes infected in vitro was also inhibited. The results suggest that early association of lymphocytes with virus inhibits the function of the cell and contributes to persistent carrying of virus in congenital rubella. This phenomenon may be a means of detecting viruses not now recognizable by routine methods of tissue culture.

A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results.

We report the data from the guideline-compliant two-year toxicology study conducted as part of the Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA). BPA (0, 2.5, 25, 250, 2,500, and 25,000 µg/kg body weight (bw)/day) was administered daily by gavage in 0.3% carboxymethylcellulose vehicle to NCTR Sprague-Dawley rats from gestation day 6 through the start of parturition and then directly to pups from the day after birth until postnatal day 21 (stop-dose arm) or continuously until termination at one or two years. The stop-dose arm was included to assess the potential for any BPA effects that were due to developmental exposure. No BPA-related effects were evident in the in-life and non-histopathology data. Neoplastic and nonneoplastic lesions diagnosed in both females and males were common age-associated lesions that were variable across control and BPA-treated groups. The lack of consistent responses within the continuous- and stop-dose arms within and across tissues brought into question the plausible relationship of most of these lesions to BPA treatment. There was a possible relationship between the increased incidences of lesions in the female reproductive tract and the male pituitary and exposure to the 25,000 µg BPA/kg bw/day dose level.

Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules.

We have identified a heptapeptide with high affinity to rheumatoid arthritis-associated class II major histocompatibility (MHC) molecules. Using a model of its interaction with the class II binding site, a variety of mimetic substitutions were introduced into the peptide. Several unnatural amino acids and dipeptide mimetics were found to be appropriate substituents and could be combined into compounds with binding affinities comparable to that of the original peptide. Compounds were designed that were several hundred-fold to more than a thousand-fold more potent than the original peptide in inhibiting T-cell responses to processed protein antigens presented by the target MHC molecules. Peptidomimetic compounds of this type could find therapeutic use as MHC-selective antagonists of antigen presentation in the treatment of autoimmune diseases.

Dental observations of hyper IgE disorder.

Recognition of "Jobs Syndrome" disorder may lead to better care. One of the dental manifestations reported is a high arched palate. Measurements of the maxillary arch were made to compare affected Job's patients, unaffected family members, and controls. Measurements of the palate found little difference between the three groups. DMFS, periodontal disease, and oral hygiene were evaluated with little difference between groups.

A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off.

We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma". Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was "papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant" with positive lymph nodes (2+/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare "papillary thyroid carcinoma" with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma.

Cell division in Agmenellium quadruplicatum: evidence for the negative control by a protein.

A high temperature conditional snake mutant, strain D1, of Agmenellum quadruplicatum was isolated which immediately stopped dividing following a shift to 41 degrees C following treatment with nitrosoguanidine. This mutant was stimulated to divide at 41 degrees C by the addition of inhibitors of RNA or protein synthesis: rifampicin, streptomycin, puromycin and chloramphenicol. Each of these inhibitors exhibited a discrete concentration optimum. The optimal concentration of chloramphenicol for cell division corresponded to the minimal concentrations necessary for the rapid inhibition of protein synthesis. The ability of chloramphenicol and other inhibitors to induce cell division in filaments decayed rapidly upon shifting to 30 degrees C. These results are interpreted as evidence for a protein acting as a negative regulator late in the cell cycle. At 41 degrees C, DNA was found distributed as a continuous zone throughout the length of the filaments. The addition of inhibitors of protein or RNA synthesis resulted in a rapid condensation of this nuclear material into multiple discrete nuclear regions suggesting that the negative control may be at the level of nuclear compartmentalization.

Isolation and molecular characterization of AKAP110, a novel, sperm-specific protein kinase A-anchoring protein.

Agents that increase intracellular cAMP are potent stimulators of sperm motility. Anchoring inhibitor peptides, designed to disrupt the interaction of the cAMP-dependent protein kinase A (PKA) with A kinase-anchoring proteins (AKAPs), are potent inhibitors of sperm motility. These data suggest that PKA anchoring is a key biochemical mechanism controlling motility. We now report the isolation, identification, cloning, and characterization of AKAP110, the predominant AKAP detected in sperm lysates. AKAP110 cDNA was isolated and sequenced from mouse, bovine, and human testis libraries. Using truncated mutants, the RII-binding domain was identified. Alignment of the RII-binding domain on AKAP110 to those from other AKAPs reveals that AKAPs contain eight functionally conserved positions within an amphipathic helix structure that are responsible for RII interaction. Northern analysis of eight different tissues detected AKAP110 only in the testis, and in situ hybridization analysis detected AKAP110 only in round spermatids, suggesting that AKAP110 is a protein found only in male germ cells. Sperm cells contain both RI, located primarily in the acrosomal region of the head, and RII, located exclusively in the tail, regulatory subunits of PKA. Immunocytochemical analysis detected AKAP110 in the acrosomal region of the sperm head and along the entire length of the principal piece. These data suggest that AKAP110 shares compartments with both RI and RII isoforms of PKA and may function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction.

Maternal morbid obesity: financial implications of weight management.

The objective of this study was to evaluate health outcomes and costs of pregnancies complicated by extreme maternal obesity (class III obesity, body mass index ≥ 40). We conducted a retrospective case-control descriptive study comparing extremely obese women (cases) and their infants with randomly selected controls. Health outcomes were obtained from the medical records and costs from billing data. Total costs for each mother-infant dyad were calculated. Compared with 85 controls, the 82 cases experienced higher morbidity, higher costs and prolonged hospital stay. However, 26% of cases maintained or lost weight during pregnancy, whereas none of the controls maintained or lost weight during pregnancy. When mother/infant dyads were compared on costs, case subjects who maintained or lost weight experienced lower costs than those who gained weight. Neonatal intensive care consumed 78% of total hospital costs for infants of the obese women who gained weight, but only 48% of costs for infants of obese women who maintained or lost weight. For extremely obese women, weight management during pregnancy was achievable, resulted in healthier neonatal outcomes and reduced perinatal healthcare costs.

The Tyr-MIF-1 family of peptides.

A review of research on the Tyr-MIF-1 family of peptides is presented with emphasis on Tyr-MIF-1 and its structure, passage through the blood-brain barrier, and both opiate antagonist and agonist properties. Family members MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1 are also included.

Behavioral effects of melanocyte stimulating hormone release-inhibiting factor-1 (MIF-1).

Consideration of the isolation, structure, localization, and behavioral effects of melanocyte stimulating hormone release inhibiting factor (MIF-1) is followed by a review of its opiate antagonistic and clinical effects. Evidence pertaining to various hypotheses offered in explanation of these behavioral effects is examined and evaluated. It is concluded that MIF-1 affects behavior in many instances with possible antagonistic effects as well as clinical possibilities.