The relationship between initial clinical manifestation and long-term prognosis of patients with systemic lupus erythematosus

The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.     

The improvement of the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy by the introduction of common database system for tuberculosis

OBJECTIVE: The purpose of this study was to improve the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy. SUBJECTIVE AND METHODS: We introduced the common database system for tuberculosis in three national hospitals in Hokkaido. From January 2002 to December 2003, we collected the anonymous informations of the patients with tuberculosis at the start of treatment, at the discharge and at the end of treatment. Then, we reported the enforcement rate of the standard regimen (A) as a clinical indicator periodically to three hospitals. RESULTS: Four hundred and twenty-nine patients were registered. In patients below 80 years old, the enforcement rate of the standard regimen (A) was 48.5% in 2002. The enforcement rate rose significantly to 62.7% (p = 0.0126) in 2003. In elder smear-positive patients (> or =75) and in elder smear-negative patients (> or =70), the enforcement rate was low (29.1% and 25.0%, respectively). Furthermore in young smear-negative patients (< or =29), the enforcement rate was low (28.0%). As the extent of their disease was minimal, they were treated with other regimens. In patients treated with the standard regimen (A), there were no significant differences in the frequency of adverse effects between elder patients ( 70) and other patients (< or =69). There were also no significant differences in the frequency of changing the regimen between them. Median admission period of 2002 was 114 days. In 2003, it was shortened significantly to 110 days (p = 0.0487). CONCLUSION: By the introduction of the common database system for tuberculosis, the enforcement rate of the standard regimen (A) was improved. Low enforcement rate in young smear-negative patients in an important problem to be improved in the future. The clinical indicator based on the common database system between hospitals, is useful to clarify the problems, and then to improve the quality of medical performance.     

A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility

For normal fertilization in mammals, it is important that functionally mature sperm are motile and have a fully formed acrosome. The glycosyltransferase-like gene, human polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5), belongs to the polypeptide N-acetylgalactosamine-transferase (pp-GalNAc-T) gene family because of its conserved glycosyltransferase domains, but it uniquely truncates the C-terminal domain and is expressed exclusively in human testis. However, glycosyltransferase activity of the human GALNTL5 protein has not been identified by in vitro assay thus far. Using mouse Galntl5 ortholog, we have examined whether GALNTL5 is a functional molecule in spermatogenesis. It was observed that mouse GALNTL5 localizes in the cytoplasm of round spermatids in the region around the acrosome of elongating spermatids, and finally in the neck region of spermatozoa. We attempted to establish Galntl5-deficient mutant mice to investigate the role of Galntl5 in spermiogenesis and found that the heterozygous mutation affected male fertility due to immotile sperm, which is diagnosed as asthenozoospermia, an infertility syndrome in humans. Furthermore, the heterozygous mutation of Galntl5 attenuated glycolytic enzymes required for motility, disrupted protein loading into acrosomes, and caused aberrant localization of the ubiquitin–proteasome system. By comparing the protein compositions of sperm from infertile males, we found a deletion mutation of the exon of human GALNTL5 gene in a patient with asthenozoospermia. This strongly suggests that the genetic mutation of human GALNTL5 results in male infertility with the reduction of sperm motility and that GALNTL5 is a functional molecule essential for mammalian sperm formation.O-glycosylation begins by the addition of N-acetylgalactosamine to the serine or threonine residues in the target protein. This first step occurs in the Golgi apparatus, and is mediated by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-T; EC 2.4.1.41), which transfer GalNAc from the nucleotide sugar to the acceptor residues (1). Polypeptide N-acetylgalactosaminyltransferase-like protein 5 [GALNTL5, also described as pp-GalNac-T19 (2) or GalNac-T20 (3); Refseq accession no.: {"type":"entrez-protein","attrs":{"text":"NP_660335.2","term_id":"281485547","term_text":"NP_660335.2"}}NP_660335.2] is classified as a member of the pp-GalNAc-T family because GALNTL5 possesses highly conserved catalytic domains of pp-GalNAc-T, whereas it uniquely lacks the conserved lectin domain at the C terminus. Thus far, 20 distinct pp-GalNAc-T genes have been identified in the human genome (2, 4–6). The in vitro enzymatic activities as a glycosyltransferase have been confirmed for 14 members of this family using acceptor peptide substrates (2, 7), but not identified for the other 6 members, including GALNTL5. During the preparation of this paper, it was reported that the transferase activity of GALNTL5 (GalNAc-T20) could not be detected using in vitro assays (3). The in vivo functions of these isoforms are poorly understood because of the absence of specific enzymatic activity. Meanwhile, O-fucosyltransferase 1, a member of a fucosyltransferase family, exhibits chaperon activity specific to Notch folding in Drosophila (8). One possibility is that the isoforms lacking enzymatic activities may have functions other than characteristics of glycosyltransferases, despite having typical glycosyltransferase motifs.Spermatogenesis is a complex process in which spermatogonial stem cells form spermatozoa through the proliferative phase (spermatogonia), the meiotic phase (spermatocytes), and the differentiation or spermiogenic phase (spermatids). Spermatids are connected by intercellular bridges, through which cytoplasmic constituents are shared among haploid spermatids (9). In the last spermiogenic phase, the round haploid spermatids differentiate into spermatozoa where acrosomes and tails unique and necessary for fertilization are developed. Spermatozoa are released through the seminiferous lumen into the epididymis, where they undergo further maturation and acquire motility. Sperm motility is an important factor in normal fertilization, whereas over 80% of sperm samples from infertile men demonstrate asthenozoospermia, poor sperm motility (10). Although defects of many potential genes are reported in mouse models exhibiting asthenozoospermia (11), it is rare that mutations in these genes are identified in human patients with asthenozoospermia.To investigate the biochemical machineries and biological functions of glycosylation, we performed comprehensive identification of the mammalian glycosyltransferase genes using various approaches and confirmed their enzymatic activity in vitro using biochemical methods (12). During these studies, we identified a unique isoform of the human GALNTL5 gene restricted to the human testis. However, we could not confirm the glycosyltransferase activity of GALNTL5, including whether it is a functional molecule in spermatogenesis. Therefore, using the mouse Galntl5 gene, we attempted to elucidate the biological role of GALNTL5 in spermatogenesis and found that the heterozygous mutation of Galntl5 causes male infertility by reducing sperm motility, which highly resembles human asthenozoospermia. In reference to the aberrant protein compositions of sperm from the Galntl5 heterozygous mutant mice (Ht mice), we found a patient with asthenozoospermia carrying one heterozygous nucleotide deletion at the sixth exon of the human GALNTL5 gene. Together with these data, we speculate that the function of GALNTL5 is indispensable for mature sperm formation and that GALNTL5 might have a unique role in mammalian spermiogenesis.     

Scan–rescan and inter-vendor reproducibility of neurite orientation dispersion and density imaging metrics

The reproducibility of neurite orientation dispersion and density imaging (NODDI) metrics in the human brain has not been explored across different magnetic resonance (MR) scanners from different vendors. This study aimed to evaluate the scan–rescan and inter-vendor reproducibility of NODDI metrics in white and gray matter of healthy subjects using two 3-T MR scanners from two vendors. Ten healthy subjects (7 males; mean age 30 ± 7 years, range 23–37 years) were included in the study. Whole-brain diffusion-weighted imaging was performed with b-values of 1000 and 2000 s/mm2 using two 3-T MR scanners from two different vendors. Automatic extraction of the region of interest was performed to obtain NODDI metrics for whole and localized areas of white and gray matter. The coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated to assess the scan–rescan and inter-vendor reproducibilities of NODDI metrics. The scan–rescan and inter-vendor reproducibility of NODDI metrics (intracellular volume fraction and orientation dispersion index) were comparable with those of diffusion tensor imaging (DTI) metrics. However, the inter-vendor reproducibilities of NODDI (CoV = 2.3–14%) were lower than the scan–rescan reproducibility (CoV: scanner A = 0.8–3.8%; scanner B = 0.8–2.6%). Compared with the finding of DTI metrics, the reproducibility of NODDI metrics was lower in white matter and higher in gray matter. The lower inter-vendor reproducibility of NODDI in some brain regions indicates that data acquired from different MRI scanners should be carefully interpreted.     

Kimura Disease of the Epiglottis: A Case Report and Review of Literature

Kimura disease (KD) affecting an unusual site is a diagnostic challenge. We report herein the case of a 62-year-old Japanese woman who presented with swelling of the epiglottis, resulting in airway narrowing. Microscopically, biopsied and resected specimens both revealed lymphoid proliferation of a reactive immunophenotype, accompanied by vascular proliferation, eosinophilic infiltration, and stromal sclerosis. Adjunctive immunohistochemistry with immunoglobulin E in addition to laboratory and histological findings led us to seriously consider a diagnosis of KD. The patient underwent surgical removal with postoperative steroid therapy and has no evidence of recurrence. Our experience suggests that KD is potentially fatal as well as showing difficulty in the histological diagnosis when occurring in the upper respiratory tract, such as the epiglottis. A literature review disclosed that our case is the 11th case so far reported in this location, and that KD of the epiglottis did not show any male preponderance, as seen in other places.