Expression of the glutathione S-transferase placental form in human lung carcinomas

Expression of glutathione S-transferase placental form (GST-)in human lung carcinoma tissue taken at autopsy or biopsy wasinvestigated immunohistochemically. All of 34 cases of squamouscell carcinomas, including poorly, moderatelyand well-differentiatedexamples were shown to stain positively for GST-. Poorly differentiatedadenocarcinomas were, however, negatively stained (0/5 cases),while moderately and well differentiated adenocarcinomas werefound tostain with GST- at rates of 69% (9/13 cases) and 71%(5/7 cases), respectively. Six cases of small cell carcinomasexamined were all negative. The results indicate that GST- maybe a useful marker fornon-small cell type lung cancer, especiallysquamous cell carcinoma which is in agreement with findingsfor rat lung neoplastic lesions reported previously.     

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis

The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A₂ significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA₂ lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.     

SOLITARY GASTRIC POLYPS IN THE FUNDIC GLAND AREA A Histochemical Study

Six solitary gastric polyps in the acid-secreting fundic mucosa were histo-chemically investigated using the mucin histochemistry, immunoperoxidase method, and silver methods for endocrine cells. Histologically, the polyps were grouped into three types : they largely consisted of either hyperplastic foveolar cells (group 1), normal-appearing fundic gland cells with mild cystic changes (group 2) or hyperplastic fundic gland cells with cystic dilatation (group 3). The presence of parietal cells and mucous neck cells was confirmed in all polyps by the immunoperoxidase method using parietal cell autoantibody and the paradoxical Concanavalin A staining, respectively. Regarding the endocrine component, somatostatin-containing cells, Grimelius-positive argyrophil cells, and Fontana-Masson-positive enterochromaffin cells were scattered in the fundic gland area of the polyps as well as in the surrounding normal-appearing fundic mucosa. Gastrin-containing cells were absent. In one of the group 2 polyps and both group 3 polyps, a varying number of glicentin-containing cells were found among the fundic gland components : In one polyp in group 3, glucagon immunoreactivity was detected in the glicentin-containing cells. These findings suggest that some of the polyps express characteristics of the fetal fundic mucosa, since glicentin and glucagon immunoreactivities in normal human stomach have been detected exclusively in the fetal fundus. ACTA PATHOL. JPN. 35: 831–840, 1985.     

Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells

BACKGROUND: Inflammation has been proposed to play essential roles in the pathophysiology of endometriosis, in which neutrophils and mast cells have been suggested to be involved. We studied whether the protease-activated receptor 2 (PAR2), which is activated by enzymes from neutrophils and mast cells, in endometriotic stromal cells (ESC) has any implication in the development of the disease. METHODS: Cultured ESC were stimulated with various concentrations of a specific PAR2 agonist peptide. Proliferating activity of the cells was determined using immunostaining of proliferating cell nuclear antigen (a cell proliferation marker), 5-bromo-2'-deoxyuridine incorporation into DNA and cell count. The concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme-linked immunosorbent assay kits. The phosphorylation of three mitogen-activated protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis. RESULTS: Activation of PAR2 stimulated the proliferation of ESC and the secretion of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2 stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS: The activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis by inducing the growth and inflammation of endometriotic lesions.     

An ambulatory respirometer (Hotmate) as a tool for screening of sleep apnea syndrome

The gold standard diagnostic method for sleep apnea syndrome(SAS) is overnight polysomnography(PSG), but is costly in terms of time and money. We studied the usefulness of a 24-hour ambulatory respirometer equipped with oximeter(Hotmate) for screening of SAS. Seventy-six cases of suspected SAS were enrolled(68 males and 8 females, mean age 51). The correlation between data from Hotmate and PSG was evaluated in 24 cases who underwent both of the tests for the final diagnosis of SAS. There was a good correlation between the two parameters of the data obtained by Hotmate(H) (H-apnea index(AI) vs H-desaturation index(DI)). Among 24 cases who underwent both Hotmate and PSG, there was a good correlation between the data from PSG and Hotmate(PSG-AI vs H-AI: r = 0.80, p < 0.001). Both sensitivity and specificity were highest when screening criteria of H-DI > 15 was utilized(sensitivity = 91.7%, specificity = 66.7%). Our findings suggest that the respiromonitor with oximeter is useful for the screening the patients with SAS.     

Comparison of an immunochromatography test with multiplex reverse transcription-PCR for rapid diagnosis of respiratory syncytial virus infections

A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the "gold standard" for detecting respiratory syncytial virus. Of 102 clinical samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of 23]). This test performs well enough to be used for patient care.     

Three antigenic variant groups in human respiratory syncytial virus subgroup B isolated in Japan

Summary Nineteen hybridomas producing monoclonal antibodies (MAbs) against the structural proteins of strain 58–17, a subgroup B field strain of respiratory syncytial virus (RSV) isolated in Japan, were obtained by fusion of X 63 myeloma cells with spleen cells from BALB/c mice immunized with the virus-infected HEp-2 cells. Seven clones were found to produce antibodies against the fusion protein (F), five against the large glycoprotein (G), five against the nucleoprotein (NP) and two against the 22k protein by radioimmunoprecipitation assay. By competitive binding assay with the MAbs, at least seven, two, three and one epitopes were defined on the F, G, NP and 22k protein components of subgroup B strain, respectively. Of these epitopes, three, two and one epitopes on the F, G and NP components were different from subgroup A strain, respectively. Fifty-three other field strains of subgroup B isolated in Sapporo, Japan, during nine epidemic years from 1980 to 1989, were examined for reactivity with the MAbs by ELISA. Different reactivity to one anti-NP antibody suggested that the 53 strains can be divided into three groups (B-a: 26 strains, B-b: 26 strains, and one other strain). The dominant strain prevailing during the 1984 to 1988 epidemic years had changed from B-a to B-b. All of the 53 subgroup B strains reacted similarly with the other 18 MAbs.     

Human papillomavirus 16 DNA immortalizes two types of normal human epithelial cells of the uterine cervix.

Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epithelium and squamous ectocervical epithelium, in descending order of frequency. However, previously only ectocervical cells have been clearly shown to be immortalized in vitro by the oncogenic human papillomaviruses (HPVs). This report describes the immortalization of normal human ecto- and endocervical epithelial cells by the intact HPV 16 genome. Ectocervical epithelial cells (HEC) became immortalized (HEC-16) without crisis while endocervical cells (HEN) were immortalized (HEN-16) after undergoing crisis. HEN-16 and HEC-16 contained integrated HPV 16 DNA, expressed E6 and E7 mRNA, and were aneuploid and nontumorigenic. They also expressed cytokeratins in a pattern similar to their distinct normal parental cells. These results suggest that both squamous and simple epithelial cells of uterine cervix are targets for immortalization by HPV 16.     

Malignant Brenner tumor with peritoneal metastasis

A case of malignant Brenner tumor with peritoneal metastasis in a 67-year-old woman was reported. The multilocular cystic tumor of right ovary was 420 g in weight, and their cystic walls were covered with multilayered tumor cells showing papillary pattern very frequently. The tumor was histologically transitional cell carcinoma with occasional glandular structures but no squamous differentiation corresponding to grade 2 or 3 urinary bladder carcinoma. The pattern of benign Brenner tumor was not identified, but there was some area of proliferating Brenner tumor. Immunohistochemically, carcinoembryonic antigen was detected in several tumor cells, especially in the intercellular spaces among them, and cytokeratin was detected only in some tumor cells. Ultrastructurally, the malignant Brenner tumor shared many common features with the benign one and also bladder tumor. Intercellular spaces with microvilli were frequently found and thought to be important for diagnosis. The morphologic criteria of this rare tumor are discussed.     

Immunohistochemical studies of endocrine cells in heterotopic pancreas

Summary Twenty-one specimens of heterotopic pancreas were investigated using the indirect immunoperoxidase method for insulin, somatostatin, glucagon, pancreatic polypeptide (PP) and gastrin. Ten specimens showed ducts, acini and islets, seven showed ducts and acini, and four showed a ductal component alone. Pyloric gland-like mucous glands were occasionally identified in association with the ductal component. In eight of ten lesions containing islets, the islets were round and had a clearly defined outline with many glucagon cells and either none or a modest number of PP cells (dorsal type). In the remaining two lesions, the islets showed varying sizes and irregular outline with many PP cells and a few or no glucagon cells (ventral type). In either type of islets, insulin and somatostatin were detected, but gastrin cells were absent. Some isolated endocrine cells were also present among the acinar and ductal components. Their occurrence in ducts was more frequent in lesions or areas mainly composed of the ductal compoment than in those with less prominent ductal tissue. In eight lesions a few gastrin cells were found in the ductal component which showed goblet cell metaplasia and pyloric gland metaplasia. An intimate relationship between goblet cell metaplasia and appearance of G cells is noteworthy.