Helicobacter pylori (HP)-provoked chronic active gastritis is histologically featured by regeneration/hyperplasia of foveolar cells, dense infiltration of lymphoid cells and neutrophils, and formation of lymphoid follicles. Mucosal areas with intestinal metaplasia are consistently devoid of HP infection. When bacilliform or coccoid bacteria are seen on the surface of the foveolar cells (within the mucus gel layer), we can regard them as HP. Exceptions are H. felis and Gastrospillirum hominis, seen as heavily coiled, long spiral bacteria. Histochemical techniques for identifying HP in gastric biopsy specimens include Giemsa, Warthin-Starry and Genta stains, the immunostain using polyclonal or monoclonal antibodies, and nonisotopic in situ hybridization histochemistry. The most practical and convenient method we recommend is a modified hematoxylin and eosin stain, in which the hematoxylin staining time should simply be prolonged double (e. g. from 5min to 10min). We have hypothesized that intestinal metaplasia represents a specific local immune response (adaptation) of the gastric mucosa to persistent HP infection. Intestinal metaplasia is quite active in secreting HP-specific secretory IgA, which may clear HP off the surface of metaplastic epithelia, resulting in the withdrawal of inflammatory cells and the disappearance of lymphoid follicles from the lamina propria. IgG-containing plasma cells, densely distributed in non-metaplastic gastritis, are scarcely seen within the metaplastic mucosa. A supportive immunochemical study has demonstrated that HP-specific secretory IgA is richly detected in the gastric secretion in cases with marked atrophic (metaplastic) gastritis. The number of IgE-containing plasma cells in HP-infected gastric mucosa is higher than those in HP-negative mucosa. In addition, we occasionally observe IgE-positivity along the dendritic cells in the germinal center of lymphoid follicles formed in the HP-infected gastric mucosa. Monoclonal antibodies to bacterial heat shock protein 60 are cross-reactive with the gastric foveolar cells and germinal center lymphocytes, although the incidence of epithelial positivity was not significantly different between HP-infected and HP-free gastric mucosae. These findings may suggest an allergic/autoimmune response to HP or HP-infected epithelia in HP-induced gastritis. We have reported that two types of benign gastric lesions may be provoked by local lamina proprial penetration of HP. These include gastric xanthomas and so-called "Russell body gastritis". HP antigens can immunohistochemically be detected in the cytoplasm of macrophages accumulated within these lesions.
A 56-year-old woman was diagnosed as suffering from stage IIIA multiple myeloma (MM) in January 1993. After 50Gy of radiation therapy, she underwent melphalan•prednisolone (MP) therapy and complete remission was achieved in July 1994. However, after the 16th course of MP therapy (total melphalan dose was 512mg), pancytopenia suddenly developed in September 1994 and acute promyelocytic leukemia (M3 by the FAB classification) was diagnosed with a karyotype of t (15; 17). Low dose Ara-C therapy was not effective and the patient died of sepsis. To our knowledge, this is the first case of M3 type secondary leukemia occuring after melphalan therapy had induced complete remission of MM.
To clarify the chromosome 14q32 abnormalities present in esophageal carcinoma and gastric carcinoma at the molecular level, we applied the fluorescence in situ hybridization (FISH) technique to metaphases of 16 esophageal carcinoma cell lines and used PCR-SSCP to analyze loss of heterozygosity (LOH) in 60 gastric carcinomas. Chromosome abnormalities associated with the 14q32 region occurred in 7 out of 16 esophageal cell lines. There were two different breakpoint cluster regions. One was found within or more telomeric to the variable region of the immunoglobulin heavy chain locus. Another breakpoint was located in the region between the tcl-1 locus and the D14S19 locus. PCR-SSCP showed that 51.7% of the 60 gastric carcinomas had LOH for at least one locus on chromosome 14 q 24-32, and this region overlapped with one of the breakpoint cluster regions found in the esophageal carcinoma cell lines. Frequent genetic abnormalities around this region have been found in colorectal carcinoma, neuroblastoma, bladder carcinoma, and ovarian carcinoma by RFLP analysis and cytogenetic studies. Taking those previous studies and our results together, it is hypothesized that the telomeric region of chromosome 14 may contain a tumor suppressor gene, inactivation of which might be caused by chromosomal translocation as well as allelic loss of this region.
Small cell lung carcinoma (SCLC) is a common and frequently fatal malignancy for which there is no satisfactory treatment. The amphibian peptide bombesin and its mammalian counterpart, gastrinreleasing peptide, act as autocrine growth factors for SCLC cells. Vasoactive intestinal peptide (VIP) inhibited the growth and multiplication of a SCLC cell line, NCl-H345. VIP-induced suppression of cell proliferation was enhanced by an anti-bombesin monoclonal antibody. Isobutylmethyl xanthine (IBMX) and forskolin, which elevate intracellular cyclic (c) AMP levels, enhanced VIP-stimulated cAMP production. IBMX and forskolin inhibited cell growth and enhanced VIP-induced suppression of cell proliferation. The inhibition by VIP and other cAMP-promoting agents paralleled their ability to stimulate cellular production of cyclic adenosine monophosphate. The anti-mitogenic activity of VIP and its enhancement by anti-bombesin antibody and other cAMP-promoting agents provide a potential new approach to the treatment of SCLC.
We report the first case of recombinant interleukin-2 (rIL-2) therapy for breast angiosarcoma after mastectomy. We evaluated the changes of killing activity in peripheral blood mononuclear cells (PBMC) by the 51Cr-release assay. Daily intravenous administration of rIL-2 increased the natural killer (NK) cell population and enhanced cytotoxicity. After the cessation of daily rIL-2 administration for 4 weeks, the enhanced cytotoxicity was not maintained by weekly administration of rIL-2. Months after mastectomy, local and distal metastases were observed, despite this immunotherapy. These results suggest that immunotherapy with rIL-2 is insufficient treatment for breast angiosarcoma, and that other modalities such as chemotherapy should be taken in consideration for use in combination with immunotherapy.
Among patients who underwent total gastrectomy for gastric cancer, 102 patients who received transverse colon interposition (TCI) by the Nagamachi type II method, (48 manual and 54 mechanical) were compared with 24 patients who underwent the jejunal ρ-loop Roux en Y method. Esophageal reflux was compared between the above three methods, and the influence on the quality of life (QOL) was examined. When compared to the jejunal ρ-loop Roux en Y method, the QOL was better for patients who underwent the TCI method (p<0.01). The incidence of reflux esophagitis with the TCI method was lower than after the jejunal ρ-loop Roux en Y method (p<0.05), and was 0% for the manual method. Reflux prevention was assessed using the standard acid reflux test and the degree of esophageal reflux with the manual method was significantly lower than with the jejunal ρ-loop Roux en Y method (p<0.0001). Esophageal reflux was also less severe with the manual method than the mechanical method (p<0.05). Manometry of the replacement stomachs revealed that, even though retrograde contraction waves were not detected in the interposed colon, the high pressure zone at the esophago-interposed colonic junction played a role in preventing reflux. These findings indicate that the TCI method particularly by the manual method is a good reconstruction technique after total gastrectomy. Excellent postoperative QOL can be obtained soon after the operation, because reflux esophagitis can be almost completely prevented.
31P magnetic resonance spectroscopy (31P-MRS) can be used to asses the early response of tumors to treatment. The aim of this study was to investigate the radiation response of tumors in vivo and to correlate it with tumor growth. FM3A tumors were subcutaneously transplanted into the lower backs of C3H/He mice. Tumors were irradiated 7 days after transplantation receiving a single dose of 10Gy. In the sham irradiation control group, 31P-MRS showed that the β-ATP/Pi and PCr/Pi ratios decreased gradually as tumor size increased with time. In the radiation group, there was an initial rise and subsequent decrease of the β-ATP/Pi and PCr/Pi ratios. The maximum β-ATP/Pi ratio was observed on day 5 after irradiation. In the tumor growth delay assay using a single dose of 10Gy, the tumor did not grow up to day 11. The peak values of the β-ATP/Pi and PCr/Pi ratios after irradiation were observed before changes in tumor volume occurred. Our results suggested that changes in metabolites observed by 31P-MRS could be a useful indicator for monitoring the effects of radiation therapy, such as reoxygenation and regrowth.