Scanning Electron Microscopic Study of the Collagen Sheath of the Human Thyroid Gland and Its Disorders

A cell-maceration/scanning electron microscope (SEM) method was employed to demonstrate the collagen sheath around follicles (perifollicular sheath) of the human thyroid gland and its disorders. In the normal thyroid gland, the follicles were surrounded by spherical collagen sheaths composed of a framework of thick collagen bands 1-5 μm in width and fine solitary collagen fibrils 50-70 nm in diameter. In benign thyroid diseases (Graves\u27 disease, Hashimoto\u27s thyroiditis and adenomatous goiter), the perifollicular sheaths differed in size and in shape according to the disease, but they were always composed of thick collagen bands and fine fibrils as in the normal thyroid. On the other hand, the spaces surrounded by the perifollicular sheaths varied markedly in size in follicular adenoma, were small in oxyphilic adenoma, and irregularly shaped in embryonal adenoma. In all these adenomas, the perifollicular sheaths were mainly composed of fine fibrils 35-45 nm in diameter. In follicular carcinoma, the size and shape of the space surrounded by the perifollicular sheaths were irregular. In papillary adenocarcinoma, the collagen sheaths showed a papillary pattern. In medullary carcinoma, tumor nests were surrounded by well developed collagen sheaths. In all these carcinomas, the collagen sheaths were mainly composed of fine collagen fibrils 32-45 nm in diameter. In adenomas and follicular carcinoma, the perifollicular sheaths frequently had large holes through which the spaces surrounded by the collagen sheaths connected to each other. Such holes were, however, rare in the normal thyroid and benign non-neoplastic thyroid diseases

Job strain and smoking cessation among Japanese male employees: a two-year follow-up study

The purpose of the present study was to assess the association between job strain and smoking cessation among Japanese male employees. In 1997, a baseline questionnaire was given to 2,625 (2,113 males and 512 females) employees of an electronics firm in Gifu Prefecture, Japan. The self-administered questionnaire was a set of questions on smoking habits and consisted of items on socio-demographic variables and smoking habits, including the Japanese version of the Job Content Questionnaire (JCQ). The JCQ consists of scales of job control, job demand, supervisory support, coworker support, job insecurity, physical demands, and isometric load. A total of 733 male smokers were then followed for 2 years, with 446 completing a follow-up questionnaire in 1999 (follow-up rate, 61%). Logistic regression analyses were performed to examine associations between job strain and smoking cessation. Among the 446 participants, 38 had quit smoking. After adjusting for age ((odds ratio: OR) = 0.38, 95% (contidence interval: CI) = 0.15-0.94), men with a high level of physical demands at baseline showed a lower smoking cessation rate at follow-up than did those with a low level. However, when adjustments were made for age and other socio-demographic variables, the odds ratio of smoking cessation showed marginal significance (OR = 0.45, 95% CI = 0.16-1.29). There was no significant association between other job strain variables and smoking cessation at the 2-year follow-up. No significant association was found between job strain and change in the number of smoked cigarettes per day. The present study did not support the hypothesis that higher levels of job stressors are associated with a lower rate of smoking cessation among men.</p

Role of a forward-viewing echoendoscope in fine-needle aspiration

AbstractA prototype forward-viewing echoendoscope has been developed for therapeutic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The hard tip of the forward-viewing echoendoscope, which is shorter than that of the convex type echoendoscope, can be maneuvered flexibly. Using the forward-viewing echoendoscope, the gastrointestinal wall can be vertically punctured along the same axis as the scope, and this process is done more easily than with an oblique-viewing echoendoscope. The diagnostic accuracy of EUS-FNA with the forward-viewing echoendoscope is 97.4%, which is not significantly different to that of the oblique-viewing echoendoscope. The forward-viewing echoendoscope may be useful in situations where the location and procedure are difficult with the oblique-viewing scope, The forward-viewing echoendoscope is able to puncture the gastrointestinal wall vertically with minimal effort, therefore allowing therapeutic EUS procedures such as pseudocyst and abscess drainage, biliary drainage, and pancreatic duct drainage to be performed easily. However, a significant difference between the forward-viewing and oblique-viewing echoendoscopes in pseudocyst drainage has been reported recently. In the future, the forward-viewing and oblique-viewing echoendoscopes will probably be selectively used depending on not only lesion site but also the procedure required in individual patients, thereby facilitating various processes including puncture, tissue collection, and diagnosis, as well as therapeutic procedures

Detection and characterization of circulating immune complexes during acute exacerbation of chronic viral hepatitis.

For the detection and characterization of circulating immune complexes (CIC) in various liver diseases, a Clq binding test was used. Though the CIC level was almost normal in HB surface antigen (HBsAg) positive asymptomatic carriers, the level increased in patients with liver diseases. During acute exacerbation of chronic viral hepatitis, the CIC level reached peaks 1 to 3 weeks before and after the hepatic cell necrosis. Study of the sedimentation rates of CIC in various liver diseases showed CIC in the 19s-22s region and in the 7s-19s region. In acid buffer, CIC was dissociated into 5 to 6 components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In one case of HBsAg positive severe chronic aggressive hepatitis, CIC was composed of HBsAg, IgG and another three or four undetermined components. During acute exacerbation of chronic hepatitis, minor changes of these dissociation patterns of CIC were observed.</p

Detection of tissue T-cell in patients with chronic active hepatitis using fragmented sheep red blood cell (SRBC) membrane.

Fragmented sheep red blood cell (SRBC) membrane was used for detection of T-cells in liver biopsy specimens from patients with chronic active hepatitis. SRBC was separated with Lymphoprep, sonicated, then filtered through a 3 mu Millipore-membrane as a fragmented SRBC reagent. Tissue T-cells were stained by an indirect immunofluorescent technique using SRBC reagent and fluorescein isothiocyanate (FITC)-labelled rabbit anti-SRBC. Positively staining lymphocytes were present in portal tracts and in areas of piecemeal necrosis. There also seemed to be a positive correlation between the number of positively staining lymphocytes and the activity of chronic hepatitis; numerous lymphocytes being stained in areas of severe piecemeal necrosis. Our findings suggest that the fragmented SRBC technique for detection of T-cells is reliable and reproducible, that it could be used as a clinical routine method, and that it is useful for further elucidating the nature of host immune reactions on tissue levels.

A Systematic Approach to Timeseries Metabolite Profiling and RNA-seq Analysis of Chinese Hamster Ovary Cell Culture

Chinese hamster ovary (CHO) cells are the primary host used for biopharmaceutical protein production. The engineering of CHO cells to produce higher amounts of biopharmaceuticals has been highly dependent on empirical approaches, but recent high-throughput "omics" methods are changing the situation in a rational manner. Omics data analyses using gene expression or metabolite profiling make it possible to identify key genes and metabolites in antibody production. Systematic omics approaches using different types of time-series data are expected to further enhance understanding of cellular behaviours and molecular networks for rational design of CHO cells. This study developed a systematic method for obtaining and analysing time-dependent intracellular and extracellular metabolite profiles, RNA-seq data (enzymatic mRNA levels) and cell counts from CHO cell cultures to capture an overall view of the CHO central metabolic pathway (CMP). We then calculated correlation coefficients among all the profiles and visualised the whole CMP by heatmap analysis and metabolic pathway mapping, to classify genes and metabolites together. This approach provides an efficient platform to identify key genes and metabolites in CHO cell culture

A Case of Metastatic Fumarate Hydratase-Deficient–like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab

We report a 62-year-old male with metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) without fumarate hydratase (FH) mutation (FH-deficient–like RCC). The International Metastatic RCC Database Consortium risk score was intermediate, and immunotherapy with nivolumab and ipilimumab (Ipi/ Nivo) was initiated. Four cycles of Ipi/Nivo and 5 cycles of nivolumab resulted in a complete response of the metastases. Hypophysitis occurred as an immune-related adverse event after four cycles of Ipi/Nivo. The prognosis of patients with FH-deficient RCC is generally poor. Few reports of FH-deficient RCC successfully treated with Ipi/Nivo have been published. Ipi/Nivo can be effective for treating FH-deficient RCC

Tissue immune complexes demonstrated in the liver of patients with chronic aggressive hepatitis using FITC-labelled human Clq.

Immune complexes in liver specimens from 10 patients with chronic liver diseases [2 with chronic persistent hepatitis (CPH), 3 with chronic aggressive hepatitis (CAH) of moderate activity, 3 with CAH of severe activity, and 2 with liver cirrhosis] were examined by a technique of direct immunofluorescence using FITC-labelled human purified Clq (FITC-Clq). FITC-Clq bound to the nuclei of all cells in liver tissue. After DNase treatment, positive nuclei were absent, but positive staining with FITC-Clq remained in amorphous deposits and hepatic cell membranes in the areas of piecemeal necrosis of four CAH patients. Since FITC-Clq could not be demonstrated in the liver tissue of CPH and liver cirrhosis which contained no piecemeal necrosis, positive fluorescence in the liver of CAH patients was thought to indicate immune complexes bound to FITC-Clq. The fact that these positive substances, however, were few in number, may be the result of physiological mechanisms of immune clearance which rapidly eliminate immune complexes from the body.</p