Association of the BDNF C270T polymorphism with schizophrenia: Updated meta‐analysis

Brain‐derived neurotrophic factor (BDNF) has been suggested to play a role in the pathophysiology of schizophrenia. The C270T polymorphism (rs56164415) in the BDNF 5′‐non‐coding region has been extensively investigated for an association with schizophrenia, but with conflicting results. An updated meta‐analysis was therefore performed of 13 case–control association studies (3505 patients and 3992 controls). An association was found between the T allele and schizophrenia. The association was significant in the East Asian population, but not in the Caucasian population. It is suggested that the BDNF C270T polymorphism contributes to schizophrenia susceptibility, especially in East Asian subjects.     

Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy

We report the case of a female patient with chronic active Epstein?CBarr virus infection (CAEBV) accompanied by hemophagocytic syndrome (HPS). On admission, she presented with severe liver dysfunction and disseminated intravascular coagulation with elevation of serum IL-6, TNF-??, and IFN-?? levels. Plasma exchange (PE) followed by immunochemotherapy with prednisolone, cyclosporine A, and VP16 was performed. PE decreased serum cytokine levels dramatically and improved liver function. Following immunochemotherapy, CAEBV became inactive. Four months after discharge, however, CAEBV relapsed with HPS, and serum cytokine levels were extremely elevated again. There was no response to immunochemotherapy, and the patient died 1?day after admission. We examined the cytokines in five additional untreated-CAEBV patients and determined that they were elevated above the normal level in all patients. These results suggest that inflammatory cytokines may have roles in the development of CAEBV, and that their depletion can be an effective treatment for this disease.     

Visual acuity outcomes of anti-VEGF treatment for neovascular age-related macular degeneration in clinical trials

Japanese Journal of Ophthalmology - Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best...     

Treatment When Prognostic Factors Do Not Match St. Gallen Recommendations: Profiling of Prognostic Factors among HR(+) and HER2(−) Breast Cancer Patients

Background

The St. Gallen consensus provides treatment recommendations for breast cancer based on prognostic factors. Although many patients’ prognostic patterns are not easily matched with the prognostic patterns listed in the St. Gallen consensus, there has been no systematic investigation reporting the gap between treatment recommendations and actual postoperative treatment choices in clinical practice.

Methods

Four hundred seventy-one patients with hormone receptor-positive [HR(+)] and human epidermal growth factor receptor type 2-negative [HER2(?)] breast cancer were analyzed. These patients were classified into either the “crisp treatment group” or “fuzzy treatment group” based on the definitiveness of postoperative treatment selection based on St. Gallen treatment recommendations. The patients in the fuzzy treatment group were further classified into strata in which patients within each stratum shared the same prognostic factor patterns with similar recurrence rates.

Results

A total of 87.3 % of HR(+)HER2(?) patients were designated to the fuzzy treatment group. Four prognostic strata were constructed according to the survival tree model, and revealed that patients with poor prognostic profiles tended to receive endocrine therapy with chemotherapy. This suggests that postoperative chemotherapy is useful, although there was no statistical significance.

Conclusions

We constructed prognostic profiles of patients in the fuzzy treatment group and examined the recurrence rates associated with two treatment regimens within each prognostic profile. These findings are exploratory, but they may be useful for planning prospective studies of the effectiveness of postoperative treatment regimens among patients with a heterogeneous combination of prognostic factors.     

The mitochondrial protein frataxin is downregulated in hemodialysis patients

Background

The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD).

Methods

Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting.

Results

The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α.

Conclusion

The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.     

Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.