Histopathological studies of microtubule disassembling agent-induced myocardial lesions in rats

Microtubule disassembling agents (MDAs) such as colchicine (COL) and vincristine sulfate (VCR) are known to be cardiotoxic. However, few attempts have been made to histopathologically examine cardiac lesions induced by MDAs. In this study, we endeavored to induce myocardial injury in rats by administering MDAs and to clarify the morphological features of these myocardial lesions. Male rats were intravenously administered COL (1.00 or 1.25 mg/kg for 2 days at single daily doses) or VCR (0.50 or 0.75 mg/kg for 2 days at single daily doses). The day after administration, hearts were excised and examined histopathologically, immunohistochemically and electron microscopically. Degeneration and necrosis of myocardial cells with vacuolation were observed in rats administered COL at 1.25 mg/kg or VCR at 0.75 mg/kg. Electron microscopic examination revealed vacuoles in swollen mitochondria. Moreover, there were cells showing pyknosis and karyorrhexis in the interstitium. TUNEL and immunohistochemical staining for endothelial cells and electron microscopic examination identified the apoptotic cells in the interstitium to be vascular endothelial cells. These vascular endothelial lesions were induced by lower doses of MDAs than were myocardial lesions. Furthermore, common sites of cardiac lesions induced by MDAs had almost the same distribution as areas positive for pimonidazole, a marker of hypoxia. These findings indicate that MDAs occasionally damage mitochondria in myocardial cells, and suggest that these changes involve microcirculatory dysfunction induced by endothelial cell injury.     

A small pontine infarct on DWI as a lesion responsible for wall-eyed bilateral internuclear ophthalmoplegia syndrome

A 64-year-old man presented with alternating exotropia and bilateral medial longitudinal fasciculus (MLF) syndrome known as wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. Diffusion-weighted imaging showed a small localized lesion in the median dorsal pons, and high-resolution T2-weighted imaging revealed slight left deviation of the lesion. A small penetrating artery was assumed to be occluded at the level of the MLF decussation. The median dorsal pons appears to be a location for the lesions causing WEBINO syndrome.     

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07–41.66) was indicated, too few events (0–2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.     

Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

An autopsy case of desmoplastic malignant mesothelioma]

On November 15, 2000, a 60-year-old man was admitted to our hospital with progressive dyspnea and right chest pain. He had a 40-year history of occupational asbestos exposure, which began when he was 20 years old. On admission, his chest radiographs showed pleural effusion on the right side, and asbestos bodies were detected in his sputum. Neither a cytological examination of the pleural effusion nor a histological examination of the pleura by percutaneous pleural biopsy revealed malignant cells. In addition, we could not find any other cause for the pleural effusion (such as tuberculosis, collagen disease, or heart failure). In May 2001, the patient also developed pleural thickening and pain in the right hypochondrium, and he was readmitted to our hospital on May 21, 2001. On readmission, an enhanced abdominal CT showed multiple liver tumors, and percutaneous pleural and liver biopsies were performed. The histological findings in the pleura and liver specimens revealed hypocellular collagen tissues without malignant cells. Thus, we could not determine the main cause either of the pleural effusion or of the patient's disease. However, his condition rapidly deteriorated, and he died on August 12, 2001. At the autopsy, bilateral pleural thickening, predominantly on the right side, and invasion of the lungs were observed. The histological findings in the pleural and hepatic tissues revealed hypocellular collagen fibers with a striate pattern and areas of neoplastic spindle cells. He was diagnosed as having malignant desmoplastic mesothelioma with liver metastasis. Cases of malignant desmoplastic mesothelioma have rarely been reported in Japan.     

Chemotherapy for alpha-fetoprotein producing gastric cancers expressing human epidermal growth factor receptor 2

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patient's quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.     

The linkage among ambulance transports,death and climate parameters in Asahikawa City,Japan

Objective

The aim of this study was to investigate the linkage among climate parameters, total ambulance transports and the number of deaths in Asahikawa City in northern Japan.

Methods

Monthly data on total ambulance transports and the number of deaths from January 2004 to December 2011 were obtained from Asahikawa City Fire Department and the Asahikawa City official website. Climate parameters for the required period were also obtained from the Japan Meteorological Agency, Japan. To adjust for the population, we also used monthly population data on Asahikawa City. The linkage among climate parameters, total ambulance transports and the number of deaths was evaluated by ecological analysis.

Results

The mean air temperature in the Asahikawa area was 7.3 ± 10.1 °C. Total ambulance transports (/a hundred thousand people/day) and the number of deaths (/a hundred thousand people/day) were 10.0 ± 0.6 and 2.6 ± 0.3, respectively. Using quadratic curves, total ambulance transports and the number of deaths were weakly correlated with some climate parameters. The number of deaths was weakly and positively correlated with total ambulance transports.

Conclusion

A weak linkage among climate parameters, total ambulance transports and the number of deaths was noted in Asahikawa City, Japan. However, these associations were not as high as expected.