Neuroendocrine differentiation in 32 cases of so-called sclerosing hemangioma of the lung: identified by immunohistochemical and ultrastructural study

Thirty-two cases of so-called sclerosing hemangioma of the lung observed by light microscopy were further studied by electron microscopy and/or immunohistochemistry. Three histologic patterns were seen: hemangioma-like, papillary, and solid. The only significant component representing the nature of the lesion is characteristic round cells within the stroma in all these patterns, whereas the surface cells lining the papillary projections or cystic spaces are normal or are hyperplastic bronchioloalveolar cells with a few neuroendocrine cells. Immunohistochemical findings showed that the "stromal cells" (tumor cells) were positive for neuroendocrine markers, namely, chromogranin A (19 of 22 cases), neuron-specific enolase (24 of 24), synaptophysin (six of 10), adrenocorticotropic hormone (14 of 15), growth hormone (14 of 15), calcitonin (11 of 15), and gastrin (11 of 14). Besides, some tumor cells were positive for epithelial membrane antigen (four of four), carcinoembryonic antigen (one of four), and vimentin (one of one). All tumor cells were negative for polyclonal antikeratin antibody (25 cases), AE1 (one case), and AE3 (one case). However, in contrast to the "stromal cells," the surface cells of the cystic spaces stained positively for keratin (25 of 25 cases), AE1 (one of one), AE3 (one of one), epithelial membrance antigen (four of four), and carcinoembryonic antigen (four of four); only a few of them expressed neruoendocrine markers. Both surface and tumor cells were negative for factor VIII-related antigen (25 cases), CD31 (one case), and alpha1-antitrypsin (25 cases). Ten cases further studied by electron microscopy and six examined by ultrastructural morphometry showed that the surface cells were mainly type 2 pneumocytes containing many lamellar bodies in the cytoplasm. Lying among them, neuroendocrine cells were occasionally seen. The stromal tumor cells had no lamellar body, but dense core granules (neurosecretory granules) and microtubules. In six cases, 92.3% (345 of 374) of tumor cells contained neurosecretory granules, which were pleomorphic and 73 to 1056 nm in diameter (mean, 302 nm). Two to 193 (mean, 12) neurosecretory granules were found in each tumor cell. Both immunohistochemical findings and ultrastructural evidence indicate that so-called sclerosing hemangioma of the lung is a benign lesion composed of neoplastic neuroendocrine cells with areas of sclerosis. A suggested name for this tumor is benign neuroendocrine tumor of the lung. The differentiation between this tumor and papillary adenoma, bronchioloalveolar carcinoma, or carcinoid tumor of the lung is discussed.     

Induction of neutralizing antibody in mice by immunization with recombinant 56 kDa protein of Orientia tsutsugamushi

Anti-oriential antibody inhibits Orientia tsutsugamushi attachment to, and penetration of, host cells. However, O. tsutsugamushi antigens that induce the production of a neutralizing antibody have not been identified. The authors immunized mice and rabbits with the recombinant 56 kDa protein of O. tsutsugamushi fused to the maltose binding protein of Escherichia coli (MBP-Bor56) and analysed their effect on O. tsutsugamushi attachment to or penetration of L929 cells. O. tsutsugamushi attachment and penetration were measured by using an indirect immunofluorescent antibody assay (IFA). O. tsutsugamushi growth in L929 cells was determined by [3H]thymidine uptake assay. By IFA, we observed a 96% reduction of attachment or penetration of O. tsutsugamushi treated with rabbit anti-MBP-Bor56 sera. [3H]thymidine uptake showed that mouse anti-MBP-Bor56 sera caused a 91% reduction in O. tsutsugamushi growth, when compared to mouse anti-MBP sera. These results suggest that the 56 kDa protein of O. tsutsugamushi plays an important role in O. tsutsugamushi attachment to or penetration of cells.     

Androgen-dependent protein interactions within an intron 1 regulatory region of the 20-kDa protein gene

The 20-kDa protein gene is androgen regulated in rat ventral prostate. Intron 1 contains a 130-base pair complex response element (D2) that binds androgen (AR) and glucocorticoid receptor (GR) but transactivates only with AR in transient cotransfection assays in CV1 cells using the reporter vector D2-tkCAT. To better understand the function of this androgen-responsive unit, nuclear protein interactions with D2 were analyzed by DNase I footprinting in ventral prostate nuclei of intact or castrated rats and in vitro with ventral prostate nuclear protein extracts from intact, castrated, and testosterone-treated castrated rats. Multiple androgen-dependent protected regions and hypersensitive sites were identified in the D2 region with both methods. Mobility shift assays with 32P-labeled oligonucleotides spanning D2 revealed specific interactions with ventral prostate nuclear proteins. Four of the D2-protein complexes decreased in intensity within 24 h of castration. UV cross-linking of the androgen-dependent DNA binding proteins identified protein complexes of approximately 140 and 55 kDa. The results demonstrate androgen-dependent nuclear protein-DNA interactions within the complex androgen response element D2.     

Lifelong teetotallers, ex-drinkers and drinkers: mortality and the incidence of major coronary heart disease events in middle-aged British men

A simplified method for the preparation and long-term cultivation of granulosa-luteal cells in serum-free medium is described. The cells were harvested from women undergoing in-vitro fertilization, enriched by sedimentation and dissociated by enzymatic treatment. We demonstrated, by introducing a synthetic serum replacement (SSR2), that these primary cell cultures cultivated in monolayers on an extracellular matrix may be used in experiments exceeding 7 days with low cell loss and cell death. No adverse effect on progesterone production was found. There was a high diversity in progesterone production between cells from individual patients. After several days in culture, the cells were challenged with human chorionic gonadotrophin which revived the rapidly decreasing progesterone production. We were unable to demonstrate an increase in cell number after 7 days of cultivation when the cells were grown in medium supplemented with either serum or SSR2. The mitogens epidermal growth factor and basic fibroblast growth factor had no influence on proliferation. We also found that the present method prevents leukocyte contamination in the granulosa-luteal cell cultures. Compared with the common method based on the enrichment of granulosa-luteal cells on a density gradient (Ficoll/Percoll), this method saves time, labour and expense, in addition to augmenting purity.     

ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb

OBJECTIVE: The purpose of this study was to evaluate ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb. CONCLUSION: Although rare, the diagnosis of ectopic drainage of the common bile duct into the duodenal bulb is important to prevent inadvertent damage during biliary tract or gastric surgery and to clarify the cause of chronic peptic ulcers.     

Mitomycin-C in congenital glaucoma

BACKGROUND AND OBJECTIVE: To evaluate the adjunctive use of mitomycin-C (MMC) during trabeculotomy and trabeculectomy for eyes with high-risk congenital glaucoma. PATIENTS AND METHODS: A prospective, randomized, double-blind study was performed to compare the effect of a single, 4-minute intraoperative exposure to 0.2 mg/ml (group 1) or 0.4 mg/ml (group 2) of MMC on trabeculotomy with trabeculectomy in 16 high-risk cases (30 eyes) of congenital glaucoma. RESULTS: The preoperative and final postoperative intraocular pressures (IOPs) of the two groups did not differ significantly. At the final follow-up, IOP control (< 21 mm Hg) without medications was achieved in 60% of the eyes in group 1 and in 86.67% of the eyes in group 2 (P = 21). With medication, IOP control was achieved in 86.7% of the eyes of each group. In both groups, the rate of surgical failure was 13.3%. Avascular, thin, sharply demarcated blebs were noted in 33.3% of the eyes from group 1 and in 66.67% of those from group 2 (P = .14). Intraoperative and postoperative hyphema and postoperative hypotony were the complications encountered in both groups, whereas serous choroidal detachment and wound leakage were seen only in group 2. CONCLUSIONS: Intraoperative MMC applied at a concentration of 0.2 mg/ml controlled postoperative IOP as effectively as a 0.4-mg/ml concentration in high-risk cases of congenital glaucoma, but with a lower incidence of complications and thin-walled blebs.     

Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma

PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Healthy aging. A women''s issue

In this thesis, Korean prisoners' health behavior and the characteristics of their medical utilization were surveyed and analysed. Because prisoners are inclined to be mediators of communicable diseases or unhealthy behaviors between prison institution and the outside world, health care for prisoners is directly related to the national population. Data were collected through a self-administered survey of 5 Korean prisons out of a total of 38 correctional facilities and analysed in accordance with a causal model based on a path frame, by serial multiple regressions on health behavior, health status, and medical utilization, etc. According to the survey analysis, while prisoners were generally concerned with their health much more than they were before imprisonment, they perceived that their health status had deteriorated after imprisonment, and that their need for health services was increasing gradually during their time in prison. In the path analysis on the causal relations among variables related to the prisoners' health status and medical utilization, the prisoners' characteristics affected their health concern and health behavior, and subsequently affected their health status and medical utilization, respectively. To sum up these exploratory studies on prisoners' health behavior and health service utilization, some efforts to organize a health care system embracing the correctional institution and health care administration should be made on the level of establishing a health care delivery system for special social groups like prisoners.