Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone.

Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a chronic pathological condition. In this study it was also shown that progesterone, estrone, and estradiol as well as androgen concentration increased in the follicle after PMSG treatment. With DHEA treatment, the follicular cystic fluid concentrations of these steroids progressively increased to extremely high levels concurrent with the development of the follicular cysts.(ABSTRACT TRUNCATED AT 400 WORDS)     

The nationwide epidemiological study of mental disorders in korea

The lifetime prevalences of DSM-III mental disorders using Korean version of DIS-III are presented. They were studied in 5,100 adults (aged 18 to 65) in household selected by two stage cluster sampling. Comparisons were made between regions, sex and age groups. International comparison with Epidemiologic Catchment Area program was also made.     

Evaluation of the Toa E-5000 Automated Hematology Analyzer

A three-phase evaluation of the Toa E-5000 Automated Hematology Analyzer was performed. The first phase consisted of evaluation of linearity, carryover, precisions, accuracy, sample stability, and effectiveness of the mixing and sampling mechanism. The second phase was comparison of erythroid and platelet parameters with results from a Coulter Counter Model S-Plus IV. The third phase consisted of comparison of the trimodal leukocyte differential count of the Toa E-5000 in 300 patients with four other differential methods. The first-phase studies showed excellent performance characteristics. Stability of samples at room temperature was good for a minimum of 12 hours, but storage for longer than 12 hours requires refrigeration to maintain stable values. The erythrocyte and platelet parameters showed good correlation with the Coulter S-Plus IV values except for the erythrocyte distribution width that is calculated differently. The third-phase studies are published elsewhere.     

Autopsy study of small cardiac scars in Japanese men who lived in Hiroshima, Japan and Honolulu, Hawaii

Japanese men long resident in Honolulu, Hawaii have significantly more ischemic heart disease but significantly fewer small cardiac scars than men in Hiroshima, Japan. These scars occur in three forms:(1)small scars in the mural myocardium which account for the difference in frequency of small lesions in the two cities and are of uncertain etiology; (2)areas of diffuse fibrosis in the papillary muscles. These are equally frequent in the two cities and are associated with advancing age and sclerosis of papillary muscle arteries; and(3)focal scars in the papillary muscles. These are more frequent in Honolulu than Hiroshima. They are healed infarcts due to ischemic heart disease and are associated with a severe degree of extramural coronary artery atherosclerosis. Small mural myocardial scars, when present, are usually found in multiple sites. Their increased frequency in Hiroshima is not explained by differences in age or heart weight. They are more common in the presence of sclerosis of intramural small arteries, but this association also fails to explain the intercity difference. It is supected that the excess of these small cardiac scars in Hiroshima males reflects past privation. There is no evidence that is is related to A-bomb radiation exposure.     

Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease

4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2mg of TNBS in 35% ethanol using a vinyl catheter positioned 4cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-gamma) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4(+)CD25(+) T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-gamma and proportion of CD8(+) T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4(+)CD25(+) regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD.     

Preoperative gentling does not attenuate septal-lesion induced hyperreactivity

Rats were either gentled or not gentled for 10 minutes a day for 7 days. At the end of this time a lesion was made in the region ventral to the anterior septum or in the lateral septum, or the rat was given a sham lesion. Reactivity to the experimenter was tested at 2, 7, and 14 days postoperatively. The reactivity scores of animals gentled preoperatively were not different from those of animals which had not been gentled but the animals of both groups were significantly more reactive than animals given a sham lesion. It is concluded that preoperative handling does not attenuate the increase in defensive behavior induced by lesions of the lateral septum or of the region ventral to the anterior septum.     

An open, randomized, comparative study of clarithromycin and erythromycin in the treatment of children with community-acquired pneumonia.

BACKGROUND AND PURPOSE: This study aimed to evaluate the efficacy and safety of clarithromycin and erythromycin in the treatment of community-acquired pneumonia in children. METHODS: Children with community-acquired pneumonia were randomly assigned to receive 10-day regimens of either clarithromycin 15 mg/kg/day, twice a day, or erythromycin 30-50 mg/kg/day, four times daily. RESULTS: A total of 97 children entered this study, including 26 with Mycoplasma pneumoniae infection, 15 with Chlamydia pneumoniae infection, and 6 with mixed mycoplasma and chlamydia infections. Fifty and 47 children received clarithromycin and erythromycin treatment, respectively. Three children withdrew from the study because the identified pathogens were resistant to the study drugs. All 47 children with mycoplasma or chlamydia infection were cured clinically. Delayed defervescence, defined as a fever lasting for more than 72 h after treatment, was observed in 4 of 22 clarithromycin-treated children (18%) and in 3 of 15 erythromycin-treated children (20%) [p>0.05]. Gastrointestinal side effects, including vomiting, abdominal pain and diarrhea, were observed in 3 of 50 children (6%) receiving clarithromycin and in 11 of 49 children (22%) receiving erythromycin (p=0.039). Excluding children with abnormal pretreatment liver function, abnormal liver function after treatment was observed in only one child, treated with erythromycin. Post-treatment eosinophil and platelet counts were significantly elevated after treatment in both groups. CONCLUSIONS: Clarithromycin showed efficacy equivalent to erythromycin for the treatment of mycoplasma or chlamydia pneumonia in children. However, the tolerability of clarithromycin was superior to that of erythromycin.     

Clinical Comparison of Distal Pancreatectomy with or without Splenectomy

The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis.     

Autologous primary muscle-derived cells transfer into the lower urinary tract

The goal of these experiments was to establish the basic methodology for future clinical applications of muscle-derived cells (MDC) tissue engineering and gene transfer for the treatment of urological dysfunction. Primary MDC isolated via preplating techniques from adult female SD rats were transduced with retrovirus encoding the expression of beta-galactosidase reporter gene. The MDC were injected into the right and left lateral walls of the bladder and proximal urethra of the autologous animals (n = 6) with a 10 microl Hamilton micro syringe. The amount of injected MDC ranged from 1 to 2 x 10(6) cells. The injected tissue was harvested after 7, 14, and 28 days, sectioned and examined histologically for beta-galactosidase and immunohistochemically for fast myosin heavy chain specific to skeletal muscle. The tissues were also stained for anti-CD4 and anti-CD8 antibodies to assess for cellular immune reaction. We have detected a large number of autologous MDC expressing beta-galactosidase and positively stained for fast myosin heavy chain in the bladder and urethral wall. Many injected myoblasts and myotubes were also seen in the bladder and urethral wall at each time point. Staining of lymphocytes with anti-CD4 and anti-CD8 antibodies was negative after MDC injection at each time point. We have demonstrated the long-term survival of autologous MDC and MDC mediated gene transfer into the bladder and urethral wall. Autologous MDC and MDC mediated gene transfer may be a promising treatment to augment bladder and urethral sphincter function.     

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population

Summary Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40–59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/–, 54%; –/–, 35% (+ and – indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p<0.05).