WIDESPREAD ECZEMA VACCINATUM ACQUIRED BY CONTACTS A Report of an Autopsy Case

A4-moth-old male infant predisposed to allergic dermatitis acquired widespread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease. ACTA PATH. JAP. 29 : 435–455, 1979.     

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients. Received: February 6, 1998 / Accepted: July, 3, 1998     

B Lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity in the tight-skin mouse

Systemic sclerosis (SSc) is characterized by fibrosis and autoimmmunity. Peripheral blood B cells from SSc patients specifically overexpress CD19, a critical cell-surface signal transduction molecule in B cells. CD19 deficiency in B cells also attenuates skin fibrosis in the tight-skin (TSK/+) mouse, a genetic model for SSc. Herein we analyzed two transgenic mouse lines that overexpress CD19. Remarkably, 20% increase of CD19 expression in mice spontaneously induced SSc-specific anti-DNA topoisomerase I (topo I) antibody (Ab) production, which was further augmented by 200% overexpression. In TSK/+ mice overexpressing CD19, skin thickness did not increase, although anti-topo I Ab levels were significantly augmented, indicating that abnormal CD19 signaling influences autoimmunity in TSK/+ mice and also that anti-topo I Ab does not have a pathogenic role. The molecular mechanisms for abnormal CD19 signaling were further assessed. B-cell antigen receptor crosslinking induced exaggerated calcium responses and augmented activation of extracellular signal-regulated kinase in TSK/+ B cells. CD22 function was specifically impaired in TSK/+ B cells. Consistently, CD19, a major target of CD22-negative regulation, was hyperphosphorylated in TSK/+ B cells. These findings indicate that reduced inhibitory signal provided by CD22 results in abnormal activation of signaling pathways including CD19 in TSK/+ mice and also suggest that this disrupted B cell signaling contribute to specific autoantibody production.     

Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients

A few studies have reported a correlation between magnesium and co-morbidity and mortality in end-stage renal disease. We investigated the prognostic value of serum magnesium concentration for mortality in 515 patients on maintenance hemodialysis (60 +/- 12 years, 306 males and 209 females; 24% diabetics). The patients underwent follow-up for 51 +/- 17 (mean +/- SD) months, and the relationship between the baseline magnesium concentration (mean of four months) and outcomes was analyzed statistically. During the follow-up period, there were 103 all-cause deaths, including 63 non-cardiovascular deaths. Kaplan-Meier analysis revealed that mortality was significantly higher in the lower magnesium group (< 2.77 mg/dL, i.e. < 1.14 mmol/L, n = 261), compared to that in the higher magnesium group (> or = 2.77 mg/dL, n = 254) (p < 0.001). Multivariate Cox proportional hazard analysis demonstrated that serum magnesium was a significant predictor for mortality (HR [per 1 mg/dL increase], 0.485 [95% CI, 0.241-0.975], p = 0.0424), particularly for non-cardiovascular mortality (HR 0.318 [95% CI, 0.132 to 0.769], p = 0.0110), after adjustment for other confounders, such as age, gender, hemodialysis duration, and the presence of diabetes. In conclusion, it is demonstrated that lower serum magnesium level is a significant predictor for mortality in hemodialysis patients, particularly for non-cardiovascular mortality, although the mechanisms remain to be explored in future studies. Factors affecting serum magnesium concentrations should be investigated in terms of better survival, including dietary magnesium intake. Further extensive studies may be also needed for possible reconsideration of the current dialysate magnesium concentration (1.0 mEq/L, i.e. 0.50 mmol/L used in most countries), one of the strong contributors to the serum magnesium concentrations of dialysis patients.     

Therapeutic effects of the combined androgen blockade therapy versus luteinizing hormone-releasing hormone analog monotherapy in patients with hormone naïve metastatic prostate cancer: a multi-institutional comparative analysis

BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.     

Dose the serum brain natriuretic peptide (BNP) level after open heart surgery reflect myocardial protection?

This clinical study was conducted to determine whether the serum BNP level after open heart surgery reflects myocardial protection. The levels of BNP and CPK-MB were measured before and after 12 hours of cardiopulmonary bypass, then 1, 3, and 6 days after open heart surgery, and the relationship between the maximum levels of BNP and the CPK-MB after open heart surgery was examined. The patients were divided into two groups according to whether or not the maximum CPK MB was more than 100 IU/l after open heart surgery. A significant relationship between the maximum BNP and the maximum CPK-MB after open heart surgery was observed (p = 0.013). Moreover, the BNP was significantly increased in the group of patients with a maximum CPK-MB > or = 100 IU/l, compared to that in those with a maximum CPK-MB < 100 IU/l, 12 hours 1 day, and 6 days after open heart surgery (p < 0.01). These findings indicate that the serum level of BNP after open heart surgery can reflect myocardial protection.