Histamine ameliorates anti-glomerular basement membrane antibody-induced glomerulonephritis in rats

Anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis involves T-helper type 1 (Th1) responses leading to rapid crescent formation. As many inflammatory and immune responses in general are affected by histamine, we examined the effects of histaminergic ligands on immune renal injury in the rat. Female Wistar-Kyoto rats were injected intraperitoneally with an antibody against the GBMs. Histaminergic ligands were then injected twice daily for 5 days after which renal function was assessed by proteinuria. Treatment with histamine led to significant dose-dependent reductions in proteinuria compared to the control antibody-injected group and markedly decreased the number of crescentic glomeruli and macrophage infiltration of the glomeruli. Furthermore, histamine significantly decreased the plasma concentration of interleukin-12, a Th1-type cytokine compared to the antibody-injected control animals. Dimaprit, an H(2)/H(4) agonist, mimicked the effects of histamine on proteinuria and crescent formation. Clozapine, an H(4) agonist, tended to mimic the effects of histamine, whereas an H(1), mepyramine, or an H(2) antagonist, ranitidine, did not reverse the protective effect of histamine. We suggest that histamine may alleviate renal injury in anti-GBM glomerulonephritis by suppressing the immune response.     

Idiopathic nodular glomerulosclerosis: three Japanese cases and review of the literature

Idiopathic nodular glomerulosclerosis (ING) is characterized as diffuse nodular glomerulosclerotic lesions, closely resembling Kimmelstiel-Wilson lesions without diabetic mellitus. We report here three Japanese cases of ING and discuss the previous reports. The patients were 75-, 48- and 84-year-old males with a history of long-term hypertension. Laboratory examination revealed moderate proteinuria and mild renal dysfunction. Diabetes mellitus was excluded by repeated clinical and laboratory investigations. Renal histology revealed nodular glomerulosclerosis, and both afferent and efferent arteriolosclerosis in all patients. In electron microscopy, the glomerular basement membrane was markedly thick in all patients. A low-protein diet and potent anti-hypertensive treatment using angiotensin-converting enzyme inhibitors were initiated in all patients and urinary protein excretion significantly reduced without the progression of renal dysfunction. We reviewed 42 previously reported cases and our three cases. The analysis revealed that common clinical features of ING are being male (82.2%) of relatively advanced age (mean age 61.3 years), with hypertension (82.2%), mild renal dysfunction (mean serum creatinine 2.9 mg/dl) and moderate urinary protein excretion (mean 4.05 g/day). Common histopathological findings of ING are nodular glomerulosclerosis (100%), arterio-arteriolosclerosis (91.2 and 89.7%) and glomerular basement membrane thickening (85.7%). In conclusion, ING is one of the phenotypes of arteriosclerotic renal disease without diabetes mellitus. Severe arterio-arteriolosclerosis may contribute to the progression to glomerular nodular formation in ING. The combination of renin-angiotensin system inhibition and a low protein diet can be beneficial for the reduction of urinary protein excretion.     

Clinical features and outcome of T-lineage acute lymphoblastic leukemia in adults: a low initial white blood cell count, as well as a high count predict decreased survival rates

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.     

SCCmec typing and detection of VISA-related genes in methicillin-resistant Staphylococcus aureus clinical strains from Kobe University Hospital, Japan

A total of 50 clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) were collected from Kobe University Hospital in 2003. Molecular typing of SCCmec was performed by multiplex polymerase chain reaction (PCR) and the presence of six genes (vraR, vraG, vraA, vraF, fruA, and fruB) associated with vancomycin (VCM) resistance was examined by simple PCR analysis. Out of 50 MRSA strains isolated 47 strains contained Type II SCCmec and the remaining contained Type IV SCCmec. Thirty seven strains contained pUB110 plasmid. VraA was present in 69% of the strains, vraF in 10%, vraG in 53%, and vraR in 16%. Noteworthy, strains without pUB110 contained vraR in relatively higher frequency (31%) compared with strains with pUB110 (11%).     

Interkinetic nuclear migration during early development of midgut and ureteric epithelia

Interkinetic nuclear migration (INM) is a well-known phenomenon that accompanies progenitor expansion in the vertebrate neural tube and non-neural ectoderm-derived epithelial tissues. In INM, progenitor cell nuclei migrate along the apicobasal axis of the epithelial layer in synchrony with cell cycle progression, resulting in ‘pseudostratification’. Although INM has long been considered a general feature of epithelial development, detailed characteristics of INM in the gut and ureteric epithelia are little known. In this study, we observe pseudostratification in the developing midgut and ureteric epithelial progenitors by scanning electron microscopy and assess their cell cycle duration by 5-bromo-2′-deoxyuridine labeling. By applying multi-dimensional scaling, we demonstrate the roundtrip migration of nuclei between the basement membrane and the apical side in the developing midgut. Partial INM has been also shown for the ureteric epithelial nuclei. Our findings reveal INM in gut and ureteric progenitors that is similar to that in ventricular neurogenesis, and suggest that INM is a general strategy for the expansion of epithelial progenitors.     

Organic cation transporter 2 and tumor budding as independent prognostic factors in metastatic colorectal cancer patients treated with oxaliplatin-based chemotherapy

Oxaliplatin is currently approved for patients with metastatic colorectal cancer (mCRC). Its uptake and consequent cytotoxicity is determined by the levels of organic cation transporter 2 (OCT2). In addition, tumor budding (TB) is associated with high malignant potential. However, the impact of the levels of OCT2 and TB on clinicopathological findings and the prognosis of mCRC patients treated with oxaliplatin-based chemotherapy remains unclear. Here, 80 mCRC patients were retrospectively assessed. Immunohistochemistry was performed to determine the levels of OCT2 and TB. High levels of OCT2 (47/80, 59%) were detected at the invasion front and were associated with depth of invasion (P=0.03), whereas high levels of TB (40/80, 50%) were associated with extensive lymphatic invasion (P=0.03). In univariate analysis, high OCT2 levels were significantly correlated with longer progression-free survival (PFS) (P=0.02) whereas high TB levels were associated with shorter PFS (P=0.01). In combined analysis, patients with 2 favorable factors (high OCT2/low TB) had longer PFS than those with 1 (P=0.03) or 0 (P<0.001) favorable factors. Multivariate analysis confirmed that the OCT2 level (P=0.007), TB level (P=0.004), and combined OCT2/TB status (P=0.001) were independent predictors for PFS. These results suggest that high levels of OCT2 indicate severe invasion, but also better prognosis in mCRC patients treated with oxaliplatin-based chemotherapy, possibly because of its role in oxaliplatin susceptibility. Combined analysis of OCT2 and TB status may guide the selection of patients for successful oxaliplatin-based chemotherapy.     

REVIEW ARTICLE: Uterine NK Cells,Spiral Artery Modification and the Regulation of Blood Pressure During Mouse Pregnancy

Citation Burke SD, Barrette VF, Gravel J, Carter ALI, Hatta K, Zhang J, Chen Z, Leno‐Durán E, Bianco J, Leonard S, Murrant C, Adams MA, Anne Croy B. Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy. Am J Reprod Immunol 2010 Reproductive success in mammals involves coordinated changes in the immune and cardiovascular as well as in the neuroendocrine and reproductive systems. This review addresses studies that identify potential links for NK cells and T cells with the local and systemic cardiovascular adaptations of pregnancy. The studies reviewed have utilized immunohistochemisty and in vivo analyses of vascular parameters by ultrasound, chronic monitoring of hemodynamics via radiotelemetric recording and intravital microscopy. At the uterine level, functional subsets of uterine natural killer cells were identified. These included subsets expressing molecules important for vasoregulation, in addition to those previously identified for angiogenesis. Spiral arteries showed conducted responses that could account for conceptus control of vasoactivity and mouse gestational blood pressure 5‐phase pattern. Vascular immunology is an emerging transdisciplinary field, critical for both reproductive immunology and cardiovascular disease.     

Practical pharmacotherapy for acute schizophrenia patients

Well‐organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute‐phase situations. Thus, practical pharmacotherapy for acute schizophrenia patients should be based on data from real clinical practice and be independent of pharmaceutical companies. This study investigated the current guidelines being used to determine the initially preferred antipsychotics, durations required before an antipsychotic is viewed as being ineffective, and the strategies utilized for early non‐responders that include switching, high dose, and augmentation. In patients who develop side‐effects to the preferred antipsychotic drug, continued use may depend on the specific characteristics of the side‐effects. For acute‐phase patients, antipsychotics with high efficacy and effectiveness may be chosen based on meta‐analysis findings for not only double‐blinded but also rater‐blinded randomized controlled trials. Many previous studies have reported being able to make an early prediction at 2 weeks regarding the later response. These predictions were supported by the findings of a recent meta‐analysis of 34 studies that examined 9975 participants. In early non‐responders to the initial antipsychotic, the effectiveness of the switching strategy appears to depend on the initial antipsychotic administered and the antipsychotic the patient is subsequently switched to. Furthermore, the effectiveness of the strategy between switching and augmentation might also depend on the initial antipsychotic administered. The current findings might serve as the basis for the use of dosing above the licensed range versus continuing the use of conventional dosing in non‐responders, provided there is close monitoring of the side‐effects. Further research is required before any modifications of routine practices are undertaken regarding the direction of new potential treatments.     

Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome

The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls. The comparison revealed that the gene frequencies and positivities of HLA-A, -B and -DR, except for DR1, had no significant differences between the patients and controls. The frequency of HLA-DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity). Although the corrected P-value (0.069) for multiple comparisons almost reached the significance level, the results indicated a possible association of the HLA-DR1 antigen with DSPS. This study suggests that there are genetic predispositions to DSPS.     

The Association Between Female Sexual Dysfunction and Sexual Dysfunction in the Male Partner: A Systematic Review and Meta-Analysis

BackgroundThe field of study addressing the relationship between FSD and male sexual dysfunction (MSD) represents a pivotal worldwide health issue as interrelationship between FSD and MSD studies are still inconclusive.AimTo review the interrelationship between FSD and MSD and to conclude whether there is a definitive risk of men developing sexual dysfunction when his partner is suffering from FSD.MethodsThe investigation was conducted following the standard practice for conducting and reporting the findings of systematic reviews and meta-analyses comprising of 4 electronic databases, that is, Embase, PsycInfo, Cochrane Library and Ovid (Medline) from inception to December 2019. Search strategies were developed based on relevant keywords with appropriate truncation and Boolean operators’ approach. The quality of studies was employed using the McMaster Critical Review Form for Quantitative Studies and were assessed by independent reviewers. The levels of evidence of the included studies were also determined.OutcomesMSD who had been exposed to FSD.ResultsFrom more than 8,000 studies searched, 26 studies were finally included, and most included studies have reasonable quality. Meta-analysis found a significant sexual dysfunction in men who are partnered with women with FSD. It found a consistent correlation between FDS and sexual dysfunction in men with a significant 3-fold increase in MSD who are partnered with women with FSD (odds ratio = 3.011, 95% confidence interval: 1.856–4.885, P = <.001, I² = 42.26%). Among subtypes of MSD, likelihood increased 4-fold for erectile dysfunction and that of premature ejaculation doubled. The data for several other domains on their components were mixed.Clinical TranslationThese findings support the notion that clinicians should evaluate sexual function pertaining to both partners and encompassing several dimensions and needing an interdisciplinary approach.Strength & LimitationsThis review exhaustively examines data search from vast electronic databases and as the comparison of studies is extracted from English journal publications, not all regions worldwide are represented.ConclusionThis meta-analysis and systematic review found an association between sexual dysfunction in men partnered with women with FSD, especially in the domains of erectile and ejaculatory function.Chew PY, Choy CL, Sidi Hb, et al. The Association Between Female Sexual Dysfunction and Sexual Dysfunction in the Male Partner: A Systematic Review and Meta-analysis. J Sex Med 2021;18:99–112.