Expression of estrogen receptor alpha (ER alpha) in the rat temporomandibular joint

Numerous epidemiological studies have pointed out a higher frequency of temporomandibular disorder (TMD) in women than in men, which indicates the involvement of a sex hormone, such as estrogen, in the pathogenesis of TMD. Although estrogen is known to play pivotal roles in osteoarthrosis or rheumatoid arthritis in systemic joints, there have been few reports about the role of estrogen in the temporomandibular joint (TMJ). The effect of estrogen is generally mediated by the estrogen receptors (ERs) ER alpha (the predominant type) and ER beta. In this study we examined the expression of ER alpha protein and mRNA in the TMJ of adult male rats by immunocytochemistry and in situ hybridization histochemistry. Intense ER alpha immunoreactivity was localized in the synovial lining cells, stromal cells in the articular disc, and chondrocytes in the TMJ. These ER alpha-immunopositive synovial lining cells are characteristic of cytoplasmic processes identified with confocal and immunoelectron microscopy, which indicates that they are synovial type B cells. In situ hybridization histochemistry confirmed intense signals for ER alpha in the synovial lining cells and the sublining fibroblasts at mRNA levels. The nuclei of chondrocytes showed an intense immunoreaction for ER alpha in the maturative and hypertrophic layers of the articular cartilage. In addition to the nuclear localization of ER alpha, a weak immunoreaction appeared in the cytoplasm of some ER alpha-positive cells. These findings support the hypothesis that TMJ tissue-at least in the male rat-has the potential to be an estrogen target tissue.     

Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels

The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8–153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29%; vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10^6.4±1.1 vs. 10^6.5±0.7 copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers. © 1996 Wiley-Liss, Inc.     

No associations found between the genes situated at 6p22.1, HIST1H2BJ, PRSS16, and PGBD1 in Japanese patients diagnosed with schizophrenia

Recent GWAS demonstrated an association between candidate genes located at region 6p22.1 and schizophrenia. This region has been reported to house certain candidate SNPs, which may be associated with schizophrenia at HIST1H2BJ, PRSS16, and PGBD1. These genes may presumably be associated with pathophysiology in schizophrenia, namely epigenetics and psychoneuroimmunology. A three-step study was undertaken to focus on these genes with the following aims: (1) whether these genes may be associated in Japanese patients with schizophrenia by performing a 1st stage case-control study (514 cases and 706 controls) using Japanese tagging SNPs; (2) if the genetic regions of interest for the disease from the 1st stage of analyses were found, re-sequencing was performed to search for new mutations; (3) finally, a replication study was undertaken to confirm positive findings from the 1st stage were reconfirmed using a larger number of subjects (2,583 cases and 2,903 controls) during a 2nd stage multicenter replication study in Japan. Genotyping was performed using TaqMan PCR method for the selected nine tagging SNPs. Although three SNPs situated at the 3' side of PGBD1; rs3800324, rs3800327, and rs2142730, and two-window haplotypes between rs3800327 and rs2142730 showed positive associations with schizophrenia, these associations did not have enough power to sustain significance during the 2nd stage replication study. In addition, re-sequencing for exons 5 and 6 situated at this region did not express any new mutations for schizophrenia. Taken together these results indicate that the genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia.     

The effect of pre-operative developmental delays on the speech perception of children with cochlear implants

Objective

The objective of this study was to evaluate the relationship between developmental delays and speech perception in pre-lingually deafened cochlear implant recipients.

Methods

This study was a retrospective review of patient charts conducted at a tertiary referral center. Thirty-five pre-lingually deafened children underwent multichannel cochlear implantation and habilitation at the Kyoto University Hospital Department of Otolaryngology-Head and Neck Surgery. A pre-operative cognitive–adaptive developmental quotient was evaluated using the Kyoto scale of psychological development. Post-operative speech performance was evaluated with speech perception tests two years after cochlear implantation. We computed partial correlation coefficients (controlled for age at the time of implantation and the average pre-operative aided hearing level) between the cognitive–adaptive developmental quotient and speech performance.

Results

A developmental delay in the cognitive–adaptive area was weakly correlated with speech perception (partial correlation coefficients for consonant–vowel syllables and phrases were 0.38 and 0.36, respectively).

Conclusion

A pre-operative developmental delay was only weakly associated with poor post-operative speech perception in pre-lingually deafened cochlear implant recipients.     

Evaluation of genetic counselling: recall of information, post-counselling reproduction, and attitude of the counsellees

Of the families who had received genetic counselling between 1972 and 1981, 791 replied to a questionnaire which covered recall of information, post-counselling reproduction and attitudes towards counselling and prenatal diagnosis. Eighty percent had adequate knowledge of mode of inheritance and 74% of recurrence risk. Knowledge of mode of inheritance was poorest in multifactorial transmission (63%) and knowledge of recurrence risk in X-chromosomal disorders (61%). Forty-five per cent of the families had started a pregnancy after the counselling. 25%). Early lethality of the disorder and feasibility of a prenatal study contributed to positive reproductive decisions. Nine per cent of the children born after the counselling were affected by the disorder in question. The observed risks tended to match well with the expected ones. Sixty-two per cent of the respondents felt that the counselling had had a great or moderate impact on their reproductive plans. Forty-two per cent expressed a wish to hear the counsellor's opinion in addition to the facts. This was more common when the disorder was severe. Although most couples (53%) wished to have a prenatal study, if feasible, and abort an affected foetus, 16% were against abortion in such a case and 31% wished to have the study but were ambiguous about an abortion.     

IMMUNOHISTOCHEMICAL DEMONSTRATION OF PEPTIDE YY IN GASTROINTESTINAL ENDOCRINE TUMORS

Fourteen cases of gastrointestinal endocrine tumors were examined im-munohistochemically for peptide YY, pancreatic polypeptide, glucagon, and somatostatin. Peptide YY cells were present in seven tumors, pancreatic polypeptide cells in eight tumors, glucagon cells in six tumors, and somatostatin cells in nine tumors. All 7 rectal endocrine tumors examined were found to contain peptide YY, while in the tumors of the other sites peptide YY cells were not detected. Peptide YY cell population in the rectal tumors was small to moderate in comparison with pancreatic polypeptide and glucagon cell population. This study suggests that peptide YY cells may be a common constituent of rectal endocrine tumors together with pancreatic polypeptide and glucagon cells, and that the peptide YY spectrum of gastrointestinal endocrine tumors may be closely related to the location of the tumors. Moreover, it can also be said that peptide YY may be used as one of the markers of rectal endocrine tumors.     

The effect of extracellular Ca2+ concentration on the negative staircase of Ca2+ transient in field-stimulated rat ventricular cells

We performed experiments using the Ca²⁺ indicator dye, fura-2 to investigate the effect of extracellular Ca²⁺ concentration ([Ca²⁺]_o) on sarcoplasmic reticulum (SR) Ca²⁺ release and loading in single rat ventricular cells. In normal Tyrode solution (1.8 mM [Ca²⁺]_o) repetitive stimulation (0.5 Hz) resulted in a gradual decrease in calcium transients (the negative staircase phenomenon) without being accompanied by a gradual decrease in diastolic intracellular Ca²⁺ concentration. The rate of the slow decline in calcium transient was faster in lower [Ca²⁺]_o. However, the peak of the first calcium transient was relatively invariant over a wide range of [Ca²⁺]_o (0.5–5 mM). The size of the calcium transient elicited by field stimulation was proportional to that induced by 10 mM caffeine, applied following the field stimulation. These results suggest that the size of calcium transients depends mainly on the Ca²⁺ content of the SR. The quiescent period favoured the replenishment of the SR and this effect was promoted further by increasing the driving force for Ca²⁺ entry across the sarcolemma during this period. We conclude that in low [Ca²⁺]_o, short stimulation interval may limit Ca²⁺ influx across the sarcolemma during the quiescent period to cause a gradual reduction in calcium content of the SR and thus the calcium transient.     

Correlation between regular mouthing movements and heart rate patterns during non-rapid eye movement periods in normal human fetuses between 32 and 40 weeks of gestation

Background

Regular mouthing movements (RMMs) are observed during fetal non-rapid eye movement (NREM) periods.

Aim

To determine the correlation between RMM and fetal heart rate (FHR) patterns during NREM periods.

Study design

Fetal eye and mouth movements and FHR patterns were observed and recorded.

Subjects

50 normal singleton pregnancies between 32 and 40 weeks of gestation.

Outcome measures

Changes in the power spectrum ratio of 3-minute blocks of RMM clusters, FHR with RMM clusters (HR +), and FHR without RMM clusters (HR −) were calculated at a frequency band of 0.02 Hz among 3 gestational age groups: group 1, 32–34 weeks gestation; group 2, 35–37 weeks gestation; group 3, 38–40 weeks gestation. We calculated the percentage of cases showing dominant peak ratios of RMM and HR + in the same frequency band, the maximum correlation coefficient, and its lag time.

Results

In group 3, the dominant peaks of both RM and HR + were present at the same frequency band, 0.06–0.08 Hz; this was not seen in the other groups' relative power spectral patterns. The percentage of cases showing dominant peaks of RMM and HR + in the same frequency band increased with advancing gestational age. The maximum correlation coefficient in groups 1 (0.28 ± 0.11) and 3 (0.45 ± 0.14) differed significantly (p < 0.05).

Conclusions

The correlation between RMM and FHR patterns became stronger, and their rhythmicity was similar, from 38 to 40 gestational weeks, suggesting that a common center starts to govern both patterns at approximately 38 weeks gestation.     

Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: Single-institute experience

Abstract:  We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m²), CY (200 mg/kg IV), and fludarabine (180 mg/m² IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21–25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.     

Combination therapy of cyclosporine with steroid inhibits γ-interferon and interleukin-1 gene expression at the level of mRNA synthesisin vivo

The present study examined the effect of cyclosporine (CsA) administered with steroidin vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to generate cytokines and their gene expression at the level of messenger RNA (mRNA). PBMC from CsA-prednisolone (Pred)-treated recipients displayed 66.9% inhibition (54.3±12.4 IU/ml;N=42;P<0.01) of -interferon (-IFN) production compared with normal individuals (134.6±18.6 IU/ml;N=23). Azathioprine (Az)-Pred-treated recipients displayed significantly less inhibition of -IFN generation (96.0±16.1 IU/ml;N=22;P<0.05) than CsA-treated patients. Macrophages (m) from CsA-Pred-treated recipients displayed 60.0% inhibition (5.1±0.7 U/ml;N=20;P<0.01) of interleukin-1 (IL-1) production compared with normal individuals (13.0±2.9 U/ml;N=21). These results were confirmed by the experiments using cDNA probe for -IFN or IL-1 (, ). High levels of -IFN mRNA in phytohemagglutinin (PHA)-stimulated PBMC or IL-1() mRNA in lipopolysaccharide (LPS)-stimulated m were present in normal individuals but not in CsA-treated recipients as judged by hybridization to a cloned human -IFN or IL-1() cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both -IFN and IL-1 gene expression at the level of mRNA at physiological concentrations.