Candidate loci for Zimmermann-Laband syndrome at 3p14.3

A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.     

Alterations in extracellular tryptophan and dopamine concentrations in rat striatum following peripheral administration of d- and l-tryptophan: An in vivo microdialysis study

Incorporation profiles of d-Trp and l-Trp into the striatum following intraperitoneal (i.p.) administration of d-Trp or l-Trp in male Sprague-Dawley rats (100 mg/kg) were investigated by using a brain microdialysis technique. Alterations in the extracellular dopamine (DA) concentration in the rat striatum were also examined. Incorporation profiles of d-Trp and l-Trp were almost identical; however, transient DA release was only observed 0–30 min following d-Trp administration. Pretreatment with 3-methylpyrazole-5-carboxylic acid, an inhibitor of d-amino acid oxidase (DAAO), significantly suppressed the DA release induced by d-Trp. These findings suggest that d-Trp-induced DA release may be mediated by certain d-Trp metabolites produced by DAAO.     

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type arising in the pleura with pleural fibrous plaques in a lathe worker

Our patient was an 86-year-old man who had worked as a lathe operator for 40 years. He had no history of tuberculosis, pyothorax, or autoimmune disease. He had not been exposed to asbestos. He was asymptomatic, but an imaging study showed gradually increasing pleural plaques. A biopsy specimen of a pleural lesion showed sclerosis of the pleura and diffuse infiltration of small- to medium-sized B lymphocytes. Polymerase chain reaction-based analysis detected monoclonal rearrangement of immunoglobulin heavy-chain genes. Histologic diagnosis was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). The lymphoma was negative for Epstein-Barr virus. We report a rare case of a metal worker with MALT lymphoma arising in the pleura with pleural fibrous plaques. It is speculated that MALT lymphoma might develop in the background of pneumoconiosis. Inflammatory and/or immunologic reactions to metal particles might contribute to the oncogenesis of this tumor.     

Volumetric Analysis of Gallbladder in Extremely Premature Infants

Background

We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants.

Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication

HIV-1 mutants escaping from HLA-A- or HLA-B-restricted CTL have been well studied, but those from HLA-C-restricted CTL have not. Therefore we investigated the ability of HLA-C-restricted CTL to select HIV-1 escape mutants. In the present study, we identified two novel HLA-Cw(*) 1202-restricted Pol-specific CTL epitopes (Pol328-9 and Pol463-10). CTL specific for these epitopes were detected in 25-40% of chronically HIV-1-infected HLA-Cw(*) 1202(+) individuals and had strong abilities to kill HIV-1-infected cells and to suppress HIV-1 replication in vitro, suggesting that these CTL may have the ability to effectively control HIV-1 in some HLA-Cw(*) 1202(+) individuals. Sequence analysis of these epitopes showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was significantly associated with the HLA-Cw(*) 1202 allele and that the V9A mutant was slowly selected in the HLA-Cw(*) 1202(+) individuals. Pol 463-10-specific CTL failed both to kill the V9A virus-infected cells and to suppress replication of the V9A mutant. These results indicate that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTL. The present study strongly suggests that some HLA-C-restricted CTL have a strong ability to suppress HIV-1 replication so that they can select HIV escape mutants as in the case of HLA-A-restricted or HLA-B-restricted CTL.     

Neuropharmacological approach against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine)-induced mouse model of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease that appears essentially as a sporadic condition. PD is well known to be a chronic and progressive neurodegenerative disease produced by a selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. The main clinical features of PD include tremor, bradykinesia, rigidity and postural instability. Most insights into pathogenesis of PD come from investigations performed in experimental models of PD, especially those produced by neurotoxins. The biochemical and cellular alterations that occur after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) treatment are remarkably similar to that observed in idiopathic PD. Furthermore, it is well known that acute treatment with MPTP can cause a severe loss of tyrosine hydroxylase and dopamine transporter protein levels and dopamine contents in the striatum of mice, as compared to continuous MPTP treatment. Thus these findings may support the validity of acute MPTP treatment model for unraveling in the neurodegenerative processes in PD. In this review, we discuss the neuroprotective effects of various compounds against neuronal cell loss in an MPTP model of PD. This review may lead to a much better understanding of PD as well as provide novel clues to new targets for therapeutic interventions in PD patients.     

A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis

A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.     

The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan

IntroductionAlthough physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear.AimTo investigate the relationship between gait function and ED in a community-dwelling population.MethodsThis cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis.Main Outcome MeasureThe main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction.ResultsOf 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5.Clinical ImplicationsThis study may motivate clinicians to investigate predictive values of physical function for ED.Strengths & LimitationsThe strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study.ConclusionsOf the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED.Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922–1929.     

The Relationships of the Maxillary Sinus With the Superior Alveolar Nerves and Vessels as Demonstrated by Cone‐Beam CT Combined With μ‐CT and Histological Analyses

There are no available detailed data on the three‐dimensional courses of the human superior alveolar nerves and vessels. This study aimed to clarify the relationships of the maxillary sinus with the superior alveolar nerves and vessels using cone‐beam computed tomography (CT) combined with μ‐CT and histological analyses. Digital imaging and communication in medicine data obtained from the scanned heads/maxillae of cadavers used for undergraduate/postgraduate dissection practice and skulls using cone‐beam CT were reconstructed into three‐dimensional (3D) images using software. The 3D images were compared with μ‐CT images and histological sections. Cone‐beam CT clarified the relationships of the maxillary sinus with the superior alveolar canals/grooves. The main anterior superior alveolar canal/groove ran anteriorly through the upper part of the sinus and terminated at the bottom of the nasal cavity near the piriform aperture. The main middle alveolar canal ran downward from the upper part of the sinus to ultimately join the anterior one. The main posterior alveolar canal ran through the lateral lower part of the sinus and communicated with the anterior one. Histological analyses demonstrated the existence of nerves and vessels in these canals/grooves, and the quantities of these structures varied across each canal/groove. Furthermore, the superior dental nerve plexus exhibited a network that was located horizontally to the occlusal plane, although these nerve plexuses appeared to be the vertical network that is described in most textbooks. In conclusion, cone‐beam CT is suggested to be a useful method for clarifying the superior alveolar canals/grooves including the nerves and vessels. Anat Rec, 299:669–678, 2016. © 2016 Wiley Periodicals, Inc.     

Neonatal estrogen treatment with β-estradiol 17-cypionate induces in post-pubertal mice inflammation in the ductuli efferentes,epididymis, and vas deferens,but not in the testis,provoking obstructive azoospermia

Neonatal estrogen treatment (NET) induces morphological changes in male reproductive organs. NET with β-estradiol 17-cypionate is reported to induce inflammation with stromal-epithelial abnormalities in the prostate and seminal vesicles in post-pubertal mice. The aim of this study was to investigate the histopathology of the testis, ductuli efferentes, epididymis, and vas deferens in mice after NET with β-estradiol 17-cypionate. No morphological changes in these organs were observed until 4 weeks after NET. However, some inflammatory cells were found in epididymis and vas deferens 6 weeks after NET. Eight weeks after NET, inflammatory cells spread to the ductuli efferentes and inflammation was severe from 6 to 12 weeks after NET. Inflammatory cells were never seen in the whole testis, but cystic dilatation of the rete testes with spermatogenic disturbance was found around the mediastinum testis. Many inflammatory cells emigrated into the lumen of the epididymis, resulting in complete absence of spermatozoa in the vas deferens. Most of the inflammatory cells penetrating into the epithelial layers of epididymal ducts were neutrophils. These results indicate that in post-pubertal mice, NET with β-estradiol 17-cypionate induces inflammation in the ductuli efferentes, epididymis, and vas deferens, but not in the testis, provoking obstructive azoospermia.