Effect of single-dose progesterone administration on estradiol receptor levels in normal human endometrium

The effects of single-dose progesterone administration on cytosolic and nuclear estradiol receptor levels (RCE2, RNE2) in normal human endometrium were studied in a group of 17 women and the results compared to 18 controls. In both groups, RCE2 and RNE2 levels were highest in the mid-cycle phase and lowest in the secretory phase. Although a wide range of values was found in both groups, the levels of RCE2 in the two groups did not differ significantly. It seems that in human endometrium a single progesterone injection does not significantly change RCE2 and RNE2 levels.     

Serological relatedness of mouse-virulent Yersinia enterocolitica.

An antiserum (WA-SAA) was produced which agglutinated specifically with mouse-virulent but not with avirulent strains of Yersinia enterocolitica. Expression of the antigenic determinant(s) reaction with WA-SAA was temperature dependent; for growth temperatures of 20 to 40 degrees C, agglutination titers were lowest for cultures grown at 20 degrees C and highest for cultures grown at 35 to 40 degrees C. Addition of Ca2+ (2.5 to 10 mM) to the growth medium had little effect on the agglutination titer, and gel diffusion studies with monospecific anti-V serum indicated that V antigen was not likely to be the determinant reacting with WA-SAA. Immunohistological studies of Peyer's patches of mice infected with Y. enterocolitica WA revealed that the antigenic determinant(s) reacting with WA-SAA was expressed in vivo. The strong correlation of agglutination titer with mouse virulence and the expression in vivo of the antigenic determinant(s) reacting with WA-SAA suggest that the antigen(s) may be associated with the pathogenicity of Y. enterocolitica.     

Islet amyloidosis in a child with type 1 diabetes

Histopathology based studies of the pancreas obtained from organ donors are increasing our awareness of islet phenotypic heterogeneity during development and aging, as well as in settings of type 1 diabetes, type 2 diabetes, monogenic diabetes or other forms of this metabolic disease. Islet amyloidosis represents a histopathological feature classically ascribed to patients with type 2 diabetes. Herein, the occurrence of islet amyloidosis and its severity are reported in a child with type 1 diabetes along with histological comparisons of islet amyloidosis in two young adults with recent-onset type 1 diabetes. Islet amyloidosis was infrequent yet widely distributed throughout the pancreas in the child with type 1 diabetes and both adults with type 1 diabetes, with no such pathology seen in matched control donors. Analysis of these cases add to the increasing appreciation of islet heterogeneity in children and young adults with type 1 diabetes. Such knowledge also supports a notion that multiple pathophysiological mechanisms underlie the loss of functional β-cell mass in the spectrum of clinical phenotypes in patients with type 1 diabetes.     

Effects of differentiation-inducing agents on purine nucleotide metabolism in an ovarian cancer cell line

The effects of the differentiation-inducing agents sodium butyrate (NaOBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine nucleotide metabolism, was studied in an ovarian carcinoma cell line (GZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and DMSO moderately decelerated purine synthesis de novo, but MA accelerated it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. NaOBt and DMSO did not affect the cellular nucleotide content, but MA caused a 73% decrease in GTP content and about a 50% increase in the cellular content of UTP. The following alterations in cellular enzyme activity were observed 72 h following exposure: NaOBt decreased the activity of hypoxanthine-guanine phosphoribosyltransferase and increased the activity of IMP and of IMP 5-nucleotidases, DMSO increased the activity of IMP 5-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line studied, the differentiation process induced by NaOBt and DMSO may be associated with a general shift in the direction of purine metabolism from anabolism to catabolism, whereas that induced by MA is associated with a specific decrease in the production of GTP.Abbreviations DMSO dimethylsulfoxide - MA mycophenolic acid - PRibPP 5-phosphoribosyl 1-pyrophosphate - NaOBt sodium butyrate - HGPRT hypoxanthine-guanine phosphoribosyltransferase     

Same-sex social behavior in meadow voles: Multiple and rapid formation of attachments

Adult meadow voles (Microtus pennsylvanicus) are solitary in the spring-summer reproductive season, but during winter months, females and males are socially tolerant and aggregate in groups. This behavioral difference is triggered by day length: female meadow voles housed in short, winter-like day lengths form same-sex partner preferences, whereas those housed in long, summer-like day lengths are less social. The present study demonstrates that same-sex social attachments in short day lengths are not exclusive; females formed concurrent attachments with more than one individual, and with non-kin as well as siblings. Partner preferences between females were established within one day of cohousing and did not intensify with greater durations of cohabitation. Males also formed same-sex social attachments, but unlike female affiliative behavior, male partner preferences were not significantly affected by day length. These data are discussed in the context of field behavior and the physiological mechanisms supporting social behavior in voles.     

Oxytocin and same-sex social behavior in female meadow voles

The neuropeptide oxytocin (OT) has been implicated in a range of mammalian reproductive and social behaviors including parent-offspring bonding and partner preference formation between socially monogamous mates. Its role in mediating non-reproductive social relationships in rodents, however, remains largely unexplored. We examined whether OT facilitates same-sex social preferences between female meadow voles—a species that forms social nesting groups in short, winter-like day lengths. In contrast to results from studies of opposite-sex attachment between prairie vole mates, we found that neither OT nor dopamine neurotransmission was required for baseline levels of social partner preference formation or expression. OT enhanced preference formation beyond baseline levels—an effect that was counteracted by treatment with an oxytocin receptor antagonist (OTA). Oxytocin receptor (OTR) density correlated with social behavior in brain regions not known to be associated with opposite-sex affiliation, including the lateral septum and central amygdala. In addition, voles housed in short day lengths (SD) exhibited higher levels of OTR binding in the central amygdala, and voles exposed to high concentrations of estradiol exhibited less binding in the nucleus accumbens (NAcc) and increased binding in the ventromedial nucleus of the hypothalamus. These results suggest that same-sex social behavior shares common elements with other mammalian social behaviors affected by OT, but that the specific neural pathways through which OT exerts its influence are likely distinct from those known for sexual attachments.     

Effect of inflammation on the ventilatory function of the eustachian tube

In an attempt to determine the effect of an upper respiratory tract infection on the ventilatory function of the Eustachian tube, 20 children who had recurrent acute or chronic middle ear effusions were studied. Baseline Eustachian tube function testing was obtained when there were no signs or symptoms of upper respiratory infection. These tests were repeated at six-week intervals and whenever an upper respiratory tract infection supervened. The results of this study were the following:

• 1 In the absence of an upper respiratory tract infection, the Eustachian tube function tests indicated that all 20 children had a persistent function al obstruction of the Eustachian tube, which was attributed to an inefficient active tubal opening mechanism or increased tubal compliance, or both.
• 3 During periods of upper respiratory tract infection, Eustachian tube function became worse, which was attributed to intrinsic mechanical obstruction.
• 3 During the course of the study, middle ear effusion or atelectasis recurred in some of the children, which was not necessarily in association with an upper respiratory tract infection.

The basic problem in all of the children was functional obstruction of the Eustachian tube that could result in a middle ear effusion; however, in the absence of an effusion, their poor Eustachian tube function would place them at particularly high risk for developing one, especially during periods of upper respiratory infection. Since management of the functional Eustachian tube obstruction remains obscure at present, therapy should be directed toward alleviating the transient or persistent middle ear negative pressure or the intrinsic mechanical Eustachian tube obstruction when an upper respiratory infection is present     

Rapid ubiquitination of Syk following GPVI activation in platelets

Spleen tyrosine kinase (Syk) activation is a key intermediate step in the activation of platelets by the physiologic agonist collagen. We have found that Syk is rapidly ubiquitinated upon activation of platelets by collagen, collagen-related peptide (CRP), and convulxin. The Src family kinase inhibitors prevented Syk phosphorylation and its ubiquitination, indicating that the process is downstream of Src kinases. The ubiquitination of Syk did not cause degradation of the protein as evidenced by the lack of effect of proteasomal and lysosomal inhibitors. We separated ubiquitinated Syk from its nonubiquitinated counterpart and used an in vitro kinase assay to compare their activities. We found that the ubiquitinated Syk appeared to be about 5-fold more active. Using a phosphospecific antibody to Syk (Tyr525/Tyr526) that measures activated Syk, we found that most (60%-75%) of the active Syk is in the ubiquitinated fraction. This result explains the apparent high specific activity of ubiquitinated Syk. In c-Cbl-deficient mice, Syk is not ubiquitinated, implicating c-Cbl as the E3 ligase involved in Syk ubiquitination. Furthermore, Syk is not dephosphorylated in these mice. We propose that c-Cbl plays a regulatory role in glycoprotein VI (GPVI)/Fc receptor gamma (FcRgamma)-chain-dependent platelet activation through its interaction with Syk.