Abstract  Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the presence of high immunoglobulin serum titers, but the mechanism by which these arise remains unclear. It has been suggested that the disease is associated with specific antibody features, including variable gene use, the presence of charged complementarity-determining region residues and/or an aberrant process of secondary light chain rearrangement. To study this in more detail, we compared variable, diversity and joining gene segment use, somatic mutation, and heavy and light chain pairings in single peripheral IgG(+) B cells between one normal (209 B cells) and two SLE (156 B cells) donors. In contrast to others, we found no systematic differences, indicating that the memory B cell repertoires in normal and SLE donors are shaped in a similar way.

Abstract  Previously, we reported that perfluorooctanoic acid (PFOA) promotes liver cancer in a manner similar to that of 17β-estradiol (E2) in rainbow trout. Also, other perfluoroalkyl acids (PFAAs) are weakly estrogenic in trout and bind the trout liver estrogen receptor. The primary objective of this study was to determine whether multiple PFAAs enhance hepatic tumorigenesis in trout, an animal model that represents human insensitivity to peroxisome proliferation. A two-stage chemical carcinogenesis model was employed in trout to evaluate PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and 8:2 fluorotelomer alcohol (8:2FtOH) as complete carcinogens or promoters of aflatoxin B(1) (AFB(1))- and/or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced liver cancer. A custom trout DNA microarray was used to assess hepatic transcriptional response to these dietary treatments in comparison with E2 and the classic peroxisome proliferator, clofibrate (CLOF). Incidence, multiplicity, and size of liver tumors in trout fed diets containing E2, PFOA, PFNA, and PFDA were significantly higher compared with AFB(1)-initiated animals fed control diet, whereas PFOS caused a minor increase in liver tumor incidence. E2 and PFOA also enhanced MNNG-initiated hepatocarcinogenesis. Pearson correlation analyses, unsupervised hierarchical clustering, and principal components analyses showed that the hepatic gene expression profiles for E2 and PFOA, PFNA, PFDA, and PFOS were overall highly similar, though distinct patterns of gene expression were evident for each treatment, particularly for PFNA. Overall, these data suggest that multiple PFAAs can promote liver cancer and that the mechanism of promotion may be similar to that of E2.

Abstract  Substantial injury can occur during reoxygenation of previously ischemic tissue in many experimental models, as the result of the generation of oxygen-derived free radicals. To test the antiradical activity of potentially protective compounds in this setting, we developed a simple screening system, applicable to fresh biopsy specimens, in which warm ischemia and reoxygenation of excised tissue are performed in vitro. Tissue production of malondialdehyde (MDA) equivalents is used as a nonspecific-but-sensitive marker of oxygen radical damage. Test compounds with putative antiradical activity are added prior to the reoxygenation phase, and their ability to suppress MDA production is an index of activity in preventing reoxygenation injury. Comparison with ischemic but not reoxygenated controls confirms the oxygen-dependent nature of the effect. Standard positive controls of known effective agents, such as butylated hydroxytoluene or deferoxamine, provide a reference for the activity of the test compound. The method is applicable to surgical biopsy specimens in veterinary and human medicine.

Abstract  Hypoxic hyperventilation in cats is a reflex normally initiated by afferent impulses originating in the carotid body and conducted to the brain stem by the carotid sinus nerves. The reflex response is abolished acutely after section of carotid sinus nerves and excision of the carotid bodies; but, chronically, there is a chemoreflex restoration which is mediated by the aortic body via the aortic depressor nerves. The restoration is associated temporally with changes in efficacy of ventilatory reflexes elicited by electrically stimulating carotid sinus and aortic depressor nerves, and these changes are postulated to reflect a central reorganization of the reflex pathways. In the present study, histological and ultrastructural techniques were used to investigate the neuroanatomical basis of the reorganization. The brain stem of the cat was examined using the Fink-Heimer silver stain to determine if degenerating axons were present following section of the carotid sinus nerve peripheral to its sensory ganglion. Degeneration was found 4-15 days postoperatively and the distribution of the axons corresponded with that reported for central projections of carotid sinus nerves labeled by transganglionic transport of horseradish peroxidase. The fine structure of nerve terminals in nucleus tractus solitarius was then examined with electron microscopy after cutting the vagus and glossopharyngeal nerves unilaterally peripheral to the sensory ganglia. Structural changes consistent with nerve terminal degeneration were observed 4-91 days postoperatively, and presumptive axonal sprouts were seen at 56-91 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  During the course of progressive Friend virus-induced leukemia in Rfv-3r/s mice, antiviral antibody caused a marked reduction in the frequency of leukemic spleen cells releasing infectious virus. We investigated the mechanism of this antibody-induced alteration of leukemia cell phenotype in a series of passive transfer experiments using monoclonal antiviral antibodies. Our results indicated that two IgG2a anti-gp70 cytotoxic antibodies could reduce the frequency of virus-producing cells within the leukemic spleen as well as maintain the virus-nonproducing phenotype once it was established. IgG2a and IgG2b monoclonal anti-p 15 antibodies, IgM, and IgA anti-gp70 antibodies, and an IgG3 anti-p 15(E) antibody were not effective. The mechanism of this phenotypic alteration appeared to involve an antibody-mediated cytostasis of virus-producing leukemia cells with the subsequent over-growth of virus-nonproducing cells. The maintenance of the virus-nonproducing phenotype was dependent on the presence of anti-gp70 antibodies capable of neutralizing and clearing infectious F-MuLV in vivo. The presence of these neutralizing antibodies appeared to prevent reinfection of virus-nonproducing cells and therefore interfered with reversion to the virus-producing phenotype.

Abstract  Milk formation in the breast during breastfeeding is a complex hormonally regulated process, potentially sensitive to the effects of endocrine-disrupting chemical exposures. The environmental chemicals, per- and polyfluoroalkyl substances (PFAS) are known endocrine disruptors. PFAS exposure have been associated with insufficient mammary gland development in mice and reduced breastfeeding duration in humans. The aim of this review was to gather the epidemiological evidence on the association between PFAS exposure and breastfeeding duration. Using PubMed and Embase, we performed a systematic literature search (on 23 January 2023) to identify epidemiological studies examining the association between maternal PFAS exposure and breastfeeding duration. Animal studies, reviews, and non-English studies were excluded. The risk of bias was assessed using the risk of bias in non-randomized studies of exposures tool. Estimates describing the association between PFAS exposure and the duration of breastfeeding were identified, and the data were synthesized separately for each type of PFAS and for the duration of exclusive and total breastfeeding. Six studies with between 336 and 2374 participants each were identified. PFAS exposure was assessed in serum samples (five studies) or based on residential address (one study). Five out of six studies found shorter total duration of breastfeeding with higher PFAS exposure. The most consistent associations were seen for perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). The finding of a potential causal association between PFAS exposure and breastfeeding duration is in agreement with findings from experimental studies.

Abstract  Correlation is a statistical method used to assess a possible linear association between two continuous variables. It is simple both to calculate and to interpret. However, misuse of correlation is so common among researchers that some statisticians have wished that the method had never been devised at all. The aim of this article is to provide a guide to appropriate use of correlation in medical research and to highlight some misuse. Examples of the applications of the correlation coefficient have been provided using data from statistical simulations as well as real data. Rule of thumb for interpreting size of a correlation coefficient has been provided.

Abstract  The study of intrahepatic bile duct epithelial cells (i.e., cholangiocytes) has been limited by the lack of a polarized in vitro model that allows easy access to both apical and basolateral cell surfaces. Therefore, we developed a cell line of polarized normal rat cholangiocytes (NRCs) and established conditions that produced a confluent monolayer of cells grown on collagen-coated filters of tissue culture inserts. We passaged NRCs at high density to collagen-coated, tissue-culture inserts and measured transepithelial electrical resistance. We evaluated ultrastructural features by transmission and scanning electron microscopy. gamma-glutamyl-transpeptidase (gamma GT) was visualized in cultured cells by enzyme histochemistry, and cytokeratin (CK)-7, CK-19, vimentin, and desmin staining was done by immunohistochemistry. We studied the biologic responsiveness and functional polarity of NRCs by measuring their levels of cyclic AMP after addition of forskolin with or without somatostatin to either the apical or basolateral chambers. When seeded with approximately 1 x 10(5) cells/cm2, the NRCs formed a confluent monolayer in 72 hr. Transepithelial electrical resistance increased over time, achieving a maximum of 625 (+- 25) ohms.cm2 by 1 week after confluence. Transmission and electron microscopy scanning showed the apical cell surface to be tightly packed with microvilli with a heterogeneous display of cilia ranging from none to 20 to 30 cilia/cell. On transmission, apically positioned tight junctions and vesicles were apparent; nuclei were oriented basally and the basolateral surface was characterized by membrane interdigitations. NRCs stained positively for the cholangiocyte marker proteins, gamma-glutamyl-transpeptidase, CK-7, and CK-19, and negative for the mesenchymal markers, vimentin, and desmin. Exposure of the basolateral (but not the apical) cell surface to somatostatin caused a 60% inhibition of forskolin-induced increases in intracellular levels of cyclic AMP, suggesting the presence of somatostatin receptors exclusively on the basolateral plasma membrane domain. We have developed a unique model of primary cultures of normal rat cholangiocytes in which the apical and basolateral surfaces are easily accessible; the cells develop intermediate-strength tight junctions, retain their cholangiocyte phenotype, display morphologic and functional polarity, and are responsive to hormones. This model should be useful for the assessment of vectorial transport of solutes and other constituents of blood and bile, as well as for studying growth regulation of cholangiocytes.

Abstract  Protease of carp retina were examined by electrophoresis and fluorogenic assays. A 70 kD serine protease with an alkaline pH optimum was detected in gelatin-containing polyacrylamide gels. A similar enzyme was found in carp brain and muscle, but not in lens. Using aminomethylcoumarin (MCA) substrates, activities that hydrolysed Z-Phe-Arg-MCA, Boc-Ala-Gly-Pro-Arg-MCA and various aminoacyl-MCAs were detected. The Z-Phe-Arg-MCA hydrolase was an acidic cysteine protease, whereas the Boc-Ala-Gly-Pro-Arg-MCA hydrolase was an alkaline cysteine protease. All aminoacyl hydrolase activities tested were inhibited by bestatin and o-phenanthroline, but not by inhibitors of serine, cysteine and aspartic proteases, suggesting they are metalloaminopeptidases. Of the substrates tested, Tyr-MCA was the most readily hydrolysed aminoacyl substrate. Preliminary evidence was obtained suggesting that levels of these activities do not differ between light- and dark-adapted retinae. The proteases have a potential involvement in retinal functioning and show similarities to other proteases known to act in the central nervous system. In particular, the Tyr-MCA hydrolase may be related to an enzyme known to remove the N-terminal tyrosine residue from enkephalin.

Abstract  We have previously demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces hemoglobin synthesis in human K562 erythroleukemia cells. The present study extends these findings by demonstrating that ara-C treatment of K562 cells results in both increased heme synthesis and accumulation of alpha-, gamma-, epsilon-, and zeta-globin RNA. The results also demonstrate that ara-C enhances K562 cell surface expression of glycophorin. Furthermore, we demonstrate that phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) inhibits the effects of ara-C on heme production, accumulation of globin RNA, and glycophorin expression. The inhibitory effect occurs maximally when K562 cells are treated with TPA before undergoing ara-C-induced commitment to erythroid differentiation. These findings suggest that TPA inhibits an early step in the process required for ara-C to enhance expression of genes involved in the erythroid program.

Abstract  One thousand five hundred and fourteen Auckland school girls in the age range 13 to 17 were given an eating attitudes test. Fourteen percent of this large population produced a score on that test of greater than 30 which has been claimed to be indicative of potential eating disorder. We view this incidence with alarm and make commentary on the social process of coupling the thin feminine body ideal with success.

Abstract  A case of arthrogryposis multiplex complex involving the temporomandibular joints is reported. The anatomy and physiopathology of the arthrogrypotic articulation are reviewed. The role of biomechanical factors in the development and maintenance of joint surfaces is discussed. Treatment modalities are proposed.

Abstract  Fifteen male schizophrenic patients between the ages of 18 and 40 were compared with 15 matched control subjects on their performance on the Facial Affect Recognition Task and on the O'Brien-Epstein Sources of Self-Esteem Inventory. As has been previously reported, schizophrenic subjects score significantly lower than normals in the recognition of emotion in the human face, particularly on the 'negative' emotions of anger, fear and disgust. Significant differences were found between groups on self-esteem domains of 'competence' and 'personal power', with normal subjects scoring higher. However, on the self-esteem scale of 'defensive self-enhancement', schizophrenic patients scored higher than the control group. Thus, the schizophrenic patients do not have uniformly lower self-esteem than normals but, rather, specific domains of self-esteem are affected. In addition, a significant negative correlation was found between affect recognition and defensive self-enhancement. The clinical-theoretical implications of working with schizophrenia are discussed in the light of these findings.

Abstract  A prospective double-blind study was carried out to compare the efficacy of intermittent versus continuous levels of beta-lactam antibiotics. Two hundred and ninety-eight patients attending their general practitioner and requiring treatment for respiratory tract infections were randomly allocated to receive either 250 mg cefaclor 3-times daily (intermittent) or 500 mg amoxycillin 3-times daily (continuous). By most of the parameters used to assess outcomes, the group on cefaclor did better than the group on amoxycillin, although in no case was the difference statistically significant. This result confirms previous studies which have shown that the maintenance of continuous levels of antibiotic is not a necessary objective when using beta-lactam antibiotics.