Effect of activated human mast cells and mast cell-derived mediators on proliferation,type I collagen production and glycosaminoglycans synthesis by human dermal fibroblasts

Although an increased number of mast cells in fibrotic tissues such as scleroderma, keloid or healing wound has been highlighted, it is still unclear whether or not mast cells are fibrogenic. The aim of the present study is to determine whether functionally active human mast cells can provide human dermal fibroblasts directly with fibrogenic properties. In order to examine the effects of IgE-mediated mast cell activation on fibroblast proliferation and synthesis of type I collagen, we utilized an in vitro defined system in which cultured human mast cells were co-cultured with human dermal fibroblasts. We also employed a three-dimensional fibroblast culture system using supplementation of L-ascorbic acid as an assay system to investigate the effects of mast cell-derived mediators on synthesis of glycosaminoglycans by human fibroblast. Fibroblast proliferation was actively stimulated with IgE-activated mast cells. However, this stimulatory effect was canceled in co-cultures with a higher number of IgE-activated mast cells. In the presence of a higher number of activated mast cells, the fibroblast cell layer was destroyed, in contrast to an intact cell layer in the presence of same number of the mast cells without activation. Type I collagen synthesis was unchanged in fibroblasts co-cultured with mast cells. The total amount of main disaccharide units, particularly DELTADi-HA, was increased when fibroblasts were exposed to histamine. Thus, we conclude that other factors, in addition to mast cells, are important in the development of human tissue fibrosis or sclerosis.     

Case report of meningoencephalitis during a concomitant mumps and parvovirus B19 infection

A 19-year-old, immunologically healthy man suffered from prolonged and intermittent high fever, left parotitis, systemic lymph node swelling, progressive liver dysfunction and leukocytopenia. 11 days after the fever onset, consciousness disturbance and generalized convulsion occurred. By the administration of γ-globulin and steroid, the patient recovered completely. Serum titers of IgG and IgM specific for both human parvovirus B19 and mumps were elevated, and parvovirus B19 DNA was identified in the serum. It was speculated that overlap infection of mumps and parvovirus B19 made the disease more severe in this patient.     

Effect of cycling experience and pedal cadence on the near-infrared spectroscopy parameters

PURPOSE: Previously we demonstrated that the method to reorder near-infrared spectroscopy (NIRS) parameters against crank angle could serve as a useful measure in providing circulatory dynamics and metabolic changes in a working muscle during pedaling exercise. To examine further applicability of this method, we investigated the effects of cycling experience and pedal cadence on the NIRS parameters. METHODS: Noncyclists (NON), triathletes (TRI), and cyclists (CYC) performed pedaling exercises at a work intensity of 75% VO2max while changing pedal cadence (50, 75, 85, and 95 rpm). Physiological and biomechanical responses and NIRS parameters were measured. RESULTS: NIRS measurements determined with the reordered NIRS change demonstrated significant differences depending on the factors. The bottom peak of reordered NIRS changes in muscle blood volume and oxygenation level shifted upward with an increase in pedal cadence in NON but remained unchanged in CYC. The reordered NIRS change demonstrated a temporary increase at the crank angle corresponding to the relaxation phase of the working muscle. This temporary increase was observed even in the highest pedal cadence in CYC. The difference in levels between the peak of the temporary increase and the bottom peak of reordered NIRS change (LPB-diff) for CYC at 85 rpm was significantly larger than that for NON. The results with NIRS parameters corresponded to changes in pedal force and myoelectric activity during pedal thrust. CONCLUSIONS: The bottom peak level of the reordered NIRS changes and LPB-diff determined for blood volume are available to detect noninvasively the differences in circulatory dynamics and metabolic change during pedaling exercises performed at different pedal cadences and also to estimate the difference of physiological and technical developments for endurance cycling in athletes.     

Mitotic activity and apoptosis in endocervical glandular lesions.

To evaluate the significance of mitotic activity and apoptosis in the differential diagnosis of endocervical glandular lesions, we examined the frequency of mitoses and apoptosis in 89 endocervical glandular lesions from 78 patients, which consisted of benign reactive changes (7 cases), lobular or diffuse laminar endocervical glandular hyperplasia (4), microglandular hyperplasia (3), tunnel clusters (7), nabothian cysts (2), mesonephric remnants (3), tubal metaplasia (3), endocervical glandular dysplasias (including atypical tubal metaplasia) (EGD) (7), adenocarcinoma in situ (AIS) (31), microinvasive adenocarcinoma (7), frankly invasive adenocarcinoma (12), and minimal deviation adenocarcinoma (3). Mitotic index (MI; mitotic figures per 1000 cells) was significantly higher in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma than any other lesions examined. Microinvasive adenocarcinoma showed the highest MI. Apoptosis was detected consistently and frequently in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma. AIS showed the highest apoptotic index (AI; apoptoses per 1000 cells). Frequent apoptotic bodies and mitotic figures are a common feature of endocervical glandular malignancies (except for minimal deviation adenocarcinoma) and are an important feature that can facilitate their differentiation from benign and borderline lesions. High MI in microinvasive adenocarcinoma might aid the distinction of microinvasive adenocarcinoma from AIS. Although both MI and AI of EGD were between those of benign reactive changes and of AIS, MI and AI alone are not sufficient to differentiate EGD from benign reactive changes. MI and AI are not helpful in the differential diagnosis between minimal deviation adenocarcinoma and its benign mimics.     

Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis.

Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis were studied in the pyloric mucosa. Young male rats were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/liter) for 14 days. Use of competitive RT-PCR and northern blotting showed that MNNG exposure induced 3- to 4-fold greater expression of the genes for integrin beta7 and integrin alphaE2 (identical with antigen OX-62, a dendritic cell marker), as well as three cytokines, IL-4, GM-CSF and TNFalpha, in the stomach pyloric mucosa of resistant Buffalo rats compared to sensitive ACI rats. These genes were minimally expressed in control animals. The results confirm the appearance of dendritic cells in the target pyloric mucosa and suggest the possibility that dendritic cell differentiation and maturation are induced by various cytokines, at least in Buffalo rats. Competitive RT-PCR showed expression of integrin alphaE2 and beta7, MHC class II-associated invariant chain (Ii), MHC class II, B7-1, CD28, GM-CSF and TNFalpha genes in all 12 examined stomach adenocarcinomas and adenomas induced in male Lewis and WKY rats with 30 weeks' MNNG exposure, suggesting the presence of dendritic cells in tumors. OX-62 staining and western blotting for OX-62 also confirmed the presence of dendritic cells in tumors. However, the population of dendritic cells in tumors was less than that in the pyloric mucosa after 14 days' MNNG exposure. The present results suggest that immune defense involving dendritic cells is marshaled from the very early initiation stage during rat stomach cancer development, but is downgraded in developed tumors.     

Height and weight change across menarche of schoolgirls with early menarche

OBJECTIVE: To describe growth before and after menarche. DESIGN: Nine hundred five fourth grade school girls were identified as a closed cohort from the first semester of 1993 for the observational study of the onset of menarche and its predictive factors. SETTINGS: Eight elementary schools in Taipei City and Taipei County, Taiwan. MAIN OUTCOME MEASURES: Data were collected from self-administered questionnaires and school records. Height and weight were measured in September, January, February, and June, or only in September and February of each year. RESULTS: All subjects remained in the cohort until sixth grade, 410 of whom had their first menstruation before graduating from elementary school. Height, weight, and body mass index (calculated as weight in kilograms divided by the square of height in meters) at each time point were plotted against 2 time scales: chronological age and time from the onset of menarche. Growth velocity of height and weight across the onset of menarche was assessed with slope change using the mixed-effect model analysis. CONCLUSIONS: The results support the hypothesis that height velocity reaches a peak 1 year before menarche but height velocity stopped increasing within 1 year after menarche. The change in weight velocity reveals no obvious growth spurt at age of menarcheal onset.     

Studies on post-transplant dyslipidemia in kidney transplant patients

This study was performed to retrospectively compare changes in the levels of total cholesterol, non-HDL cholesterol, triglycerides, and immunosuppressive drugs, cyclosporine A and steroids in patients with living-relation renal transplants with those from non-heart-beating donors. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. We evaluated 13 cases of kidney transplants from living-relation donors during the same period. The immunosuppressants used included mainly cyclosporine A as well as mycophenolate mofetil or azathioprine, steroid and ALG, or basiliximab. Over-night fasting lipids (total cholesterol, triglycerides and HDL cholesterol) were studied before renal transplantation and repeated after renal transplantation at 1, 3, 6 and 12 months. The levels of total cholesterol and triglycerides remained in the normal range before transplantation. However, the levels of total cholesterol increased siginificantly 1 and 3 months after transplantation from non-heart-beating donors and remained at higher levels up to 12 months after transplantation. A similar pattern in the levels of triglycerides was observed. The levels of HDL cholesterol remained unchanged and stayed in the normal range before and 1, 3, 6, and 12 months after transplantation from non-heart-beating donors. On the other hand, significant increases in non-HDL cholesterol were observed 3 and 6 months after transplantation from non-heart-beating donors. After transplantation from living-relation donors, levels of total cholesterol, triglycerides, and non-HDL cholesterol remained unchanged and remained in the normal range up to 12 months after transplantation. Although there were no significant differences in the total dosage of cyclosporine A between the patients with living-relation donors and those with non-heart-beating donors, a significant increase in the total dosage of methylprednisolone was observed in patients with non-heart-beating donors compared with those in the patients with living-relation donors. Renal function recovery in patients with living-relation donors was better than in those with non-heart-beating donors. These results may suggest that significant increases in total cholesterol, especially non-HDL cholesterol and triglycerides, were probably partly due to an increased use of immunosuppressants, steroids. It is necessary to aggressively control post-transplant hyperlipidemia and important to reduce or withdraw steroids in the selected, low-risk recipients as early as possible from the viewpoint of preventing post-transplant hyperlipidemia.