Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas.

The expression of LeY (Fuc alpha 1----2Gal beta 1----4 [Fuc alpha 1----3]GlcNAc beta 1----R) (in which Fuc is fucose, Gal is galactose, and GlcNAc is N-acetylglucosamine) defined by monoclonal antibody AH6 in various locations of human colonic epithelia, colonic polyps, and adenocarcinomas has been studied. In normal colonic mucosa, strong staining by AH6 was observed in the proximal regions such as the terminal ileum and cecum. The staining was, however, greatly reduced in the epithelia of the ascending colon and became very weak in the epithelia of transverse, descending, and sigmoidal colon as well as the rectum. Of 481 crypts in 40 biopsy samples of the epithelia of normal sigmoidal colon, 421 crypts did not show any staining, and only a weak staining of the lowest crypt area was observed in 60 crypts (12%); of 474 crypts in 40 biopsy samples of normal rectal epithelia, 110 crypts (26%) showed a weak staining. At the fetal stage, the LeY staining was much more intense in all locations of the colon than in corresponding locations of adult epithelia, and staining was observed in the epithelia of the sigmoidal colon and rectum. A strong staining was observed in 24 of 25 cases of colorectal adenocarcinomas, irrespective of their original location. The expression of LeY in polyps was correlated with histological type as well as the degree of dysplasia of the polyps. Of various adenomas examined, tubular adenomas, many of which showed mild or moderate dysplasia and less malignant potentials, displayed the least LeY expression. Tubulovillous and villous adenomas, which have higher malignant potential and showed a higher incidence of severe dysplasia, showed a greater area and intensity of LeY expression. No LeY was detectable in juvenile polyps, and only a very weak staining was observed in the dysplastic area of hyperplastic polyps. The extent and intensity of staining in various adenocarcinomas and adenomas could not be correlated with blood group ABO status of the hosts nor with location of the tumors. These results suggest that LeY in colonic adenocarcinomas and polyps at the distal region of the colon and rectum is a typical oncofetal antigen and is a useful marker for diagnosis of colonic cancer. Its expression in colonic polyps can be correlated with the degree of dysplasia and may indicate the degree of malignant potential of the polyp. Thus, LeY expression in polyps may have prognostic value.

Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer.

We have developed a new immunochemical test for fecal lactoferrin (LF) utilizing an enzyme-linked immunosorbent assay (ELISA). The ELISA had a sensitivity of about 10 micrograms/L of lactoferrin and the measurable range was 10.0-1000.0 micrograms/L (1.0-100.0 micrograms LF/g feces). The stability of lactoferrin in feces was greater than that of myeloperoxidase and leucocyte elastase. The fecal concentration of lactoferrin (mean +/- SD) in 35 normal subjects was 0.75 +/- 0.83 microgram/g feces, whereas that in 24 patients with colon cancer was 74.4 +/- 88.3 micrograms/g feces. The fecal lactoferrin concentration of 38 patient with active ulcerative colitis was 307.4 +/- 233.9 micrograms/g feces, and that in 36 patients with active Crohn's disease was 191.7 +/- 231.1 micrograms/g feces. The ELISA for human fecal lactoferrin might be useful in the diagnosis of colon disease.

Effects of 16, 16-dimethyl prostaglandin E2 on lysosomal membrane stability in rat stomach.

The lysosomal membrane encloses numerous hydrolytic enzymes and prevents the cytoplasm from being damaged by these enzymes. It is possible that the fragility of this membrane may be implicated in the pathogenesis of gastric mucosal damage. We investigated the effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), which is known to protect the gastric mucosa from various noxious agents, on lysosomal membrane stability in the rat stomach. Sodium taurocholate (TC) was used as the damaging agent. To assess lysosomal membrane stability in the gastric mucosa, we assayed acid phosphatase released from lysosomes isolated from a gastric mucosal homogenate. To assess lysosomal membrane stability in gastric surface epithelial cells, we used laser scanning confocal microscopy to observe the fading of red fluorescence in living cells vitally stained with acridine orange. Exogenous dmPGE2 enhanced lysosomal membrane stability in the gastric mucosa, whereas TC decreased it. In gastric surface epithelial cells, exogenous dmPGE2 protected the cells against TC-induced damage and prevented TC-induced decreased lysosomal membrane stability. It was concluded that a decrease in lysosomal membrane stability seemed to be closely involved in the pathogenesis of gastric mucosal damage. Moreover, it appears that stabilization of the lysosomal membrane by exogenous dmPGE2 may contribute to its protective effect in the gastric mucosa, both at the level of gastric surface epithelial cells and in regard to the entire gastric mucosa.

Immunochemical detection of human blood in feces.

We have developed a new immunochemical test for fecal occult blood utilizing enzyme-linked immunosorbent assay (ELISA) of human hemoglobin (HbAo) and transferrin (Tf) simultaneously. The ELISA had a sensitivity of about 15 ng/ml Hb, and the measurable range was 1.5-750 micrograms Hb per g feces. The stability of Tf in feces was greater than that of Hb. In 17 out of 18 patients with colon cancer, 8 out of 15 patients with colon polyps, and 11 out of 20 patients with upper-gastrointestinal disorders. The Hb and Tf values were more than 10 micrograms/g feces, in terms of Hb concentration. The ELISA for human fecal HbAo and Tf might be useful for the diagnosis of gastrointestinal disorders.

Duodenitis--distinguishing features in a retrospective endoscopic and histological study.

Routine films of 596 upper GI endoscopies with the diagnosis of duodenitis were reviewed and a classification was made into granular (G), multi-polypoid (MP), reddened (R) and erosive (E) types. Two hundred and thirty-four histological specimens from 117 of the patients, as well as 100 specimens from 50 controls, were analyzed for villous obliteration, Brunner's gland dilatation and mucus depletion, erosion, mucosal hemorrhage and edema, atypia of the surface epithelium and gastric surface epithelial metaplasia. Inflammatory cell counts for polymorphonuclear and mononuclear cells in the epithelium, in the lamina propria together with a histological score was also made. On the basis of this study and a review of classifications of duodenitis in the literature, it is concluded that some endoscopical features like erosions and redness may represent more acute phases of duodenitis, mucosal elevations representing more hyperplastic changes and that the endoscopic classification into G, MP, R and E types seem relevant to use in clinical practice.

A study on the effects of countermeasures for vibrating tool workers using an impact wrench.

The aims of this study were (1) to measure frequency-weighted vibration acceleration and (2) to study the effects of introducing a vibration-proof impact wrench on VWF in workers. The subject pool was 383 male workers who were regularly using an impact wrench and taking special medical examinations for vibration syndrome in a factory from 1982 to 1999. The prevalence of workers with VWF increased gradually after 1982, reached a peak value (4.8%) in 1986, gradually decreased after 1987, and disappeared in 1994. Sixteen subjects who had had VWF at least one time during the observation period were selected for this study. The stages of VWF were at stage I on the Stockholm Workshop scale in all subjects. After the vibration-proof impact wrench was introduced in 1986, the vibration acceleration of the impact wrench measured on the handle decreased from 8.6-11.1 m/s2 to 5.1-7.1 m/s2. The actual time per day that subjects were assumed to use the impact wrench was 108 minutes. The subjects actually used an impact wrench more than the occupational exposure limit allowed. However, VWF disappeared after the introduction of a vibration-proof impact wrench. This might have resulted from the combined effect of introducing the vibration-proof impact wrench and certain countermeasures that were taken against cold working environments.

Peripheral hemodynamics evaluated by acceleration plethysmography in workers exposed to lead.

To clarify the effect of lead exposure on peripheral hemodynamics, acceleration plethysmography (APG) was performed for 48 male subjects occupationally exposed to lead (exposure group) and 43 male subjects with no history of occupational exposure to lead (control group). In the exposure group, the blood lead concentration (Pb-B) was also measured. Each APG parameter was assessed by comparing measured data with the standard aging curves. A significant negative correlation was obtained between the parameter--b/a and Pb-B. The exposure group showed significantly lower values of parameters--b/a (p < 0.01) and d/a (p < 0.05) than the control group. The parameter--b/a in the exposure group dose-dependently decreased with increases in length of working career (duration of exposure to lead) and Pb-B. The parameter--b/a significantly (p < 0.05) decreased in subjects with working careers of 5 years or more and in subjects whose Pb-B was 40 micrograms/100 ml or more. These results suggest that lead exposure affects peripheral hemodynamics as evaluated by APG.

A micro-suspension-test for evaluation of disinfectants against human immunodeficiency virus.

We devised a micro-suspension-test to evaluate disinfectants against human immunodeficiency virus type-1 (HIV-1) and confirmed its reliability. Suspensions of persistently HIV-1-infected Molt-4 cells were used as targets of disinfectants and residual infectivity was measured by an infectivity assay: after cocultivation with uninfected Molt-4 cells reverse transcriptase activity (RTA) in the supernatant and giant cell formation (GCF) were monitored. Our new infectivity assay consists of a short-term assay, that is RTA and GCF monitoring on the second day of co-culture, and a long-term assay, that is RTA monitoring up to the 28th day of co-culture. The sensitivity of the short-term assay was 1 x 10(3) infected cells and that of the long-term assay 1 x 10(1) infected cells. All the chemical disinfectants examined in this study showed dose- and time-dependent inactivation of HIV-1. By 5-minute contact with ethanol, glutaraldehyde, formalin, sodium hypochlorite and povidone-iodine, HIV-1 was effectively inactivated at concentrations of 20, 0.01, 5, 0.05 and 0.1%, respectively. Since the micro-suspension-test is easy and sensitive, we recommend it as a method for evaluating disinfectants against HIV-1.

[Possibility of endoscopic treatment for early gastric cancer].

Endoscopic therapy has been aggressively used for radical treatment of early gastric cancer, because endoscopic resection allows us to collect the removed tissue and to determine histopathologically whether the cancer lesion has been completely resected. In order to succeed in radical treatment, the complete resection of lesion and no lymph node metastasis are necessary. On the basis of thorough histopathological investigations into operated cases with early gastric cancer, the types of early gastric cancer which have no lymph node metastasis are considered to be as follows: 1) Intramucosal carcinoma type I type II a, measuring 30 mm or less type II b type II c, measuring 10 mm or less 2) carcinoma invading up to submucosal layer type II a + II c, measuring 10 mm or less type II a, measuring 20 mm or less type II b type II c, measuring 10 mm or less type II a + II c, measuring 10 mm or less However, indications of endoscopic resection should be more strictly decided due to diagnostic and technical problems. Eventually, it will be important to detect and resect intramucosal gastric carcinoma as small as possible in order that the lesion be completely resected. The success of curative treatment is evaluated by not only histopathological examination of resected tissue, but also through follow-up study. Therefore, various problems remain to be resolved in this treatment. A larger case sampling will serve to confirm the reliability of this form of therapy for early gastric cancer.

[Endoscopic surgery for early gastric cancer by endoscopic mucosal resection (EMR)].

Endoscopic mucosal resection (EMR) enables one to examine resected specimens histologically and judge the curability by the histological findings. A mucosa and a part of submucosa can be resected by EMR. Therefore, mucosal cancers are indications for EMR. The present study showed that better indications for EMR were as follows: lesions less than 10 mm in size, lesions without ulceration, and lesions in the antrum or at the greater curvature. However, it is difficult to judge correctly before EMR whether the lesions are completely resected or not. The lesions with better indications are not always resected completely, and, conversely, the lesions more than 11 mm in size are completely resected at times. Therefore, it is most important to know how to deal with resected specimens. Specimens must be dealt with in strict conformity with the regulations. At present, when EMR may be regarded as the least invasive modality of curative sugeries, a new systematic treatment combining surgical laparotomic treatment and EMR is desirable for curative treatment of early gastric cancer.

[Combination chemotherapy with etoposide, ADM, and CDDP (EAP) for advanced gastric cancer].

EAP therapy has been performed on 50 cases of advanced gastric cancer from January 1988 to September 1989. Adriamycin 20 mg/m2, Cisplatin 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. Complete success, PR, NC and PD were obtained in 48, 21, 20 and 7 cases, respectively, the rate of effectiveness being 43.8% with a confidence interval 95% of 30-58%. The rate of effectiveness by lesions for evaluation was high (30.4, 100, and 50% for primary lesion, Virchow's lymphnodal metastasis and liver metastasis, respectively). MST was 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus, it is thought that good control of leukopenia, a dose limiting factor remains to be examined.

A study on gastric ulcers induced by long-term fasting in rats.

The present study was performed to investigate the roles of intragastric pH and PAS positive mucus as to the incidence of gastric ulcers after long-term fasting in rats. Gastric ulcers in the forestomach and corpus were found at 4 and 6 days after fasting, respectively. The intragastric pH was significantly reduced at 1, 2, 3, 4, 6 and 7 days after fasting, but tended to have returned to control levels at 8 days. PAS positive mucus was significantly increased at 2 to 7 days, but there was no significant change at 8 days. From these results, it seems that the aggressive factor is not involved, but attenuation of the defensive factor is important as to the incidence of this type of ulcer. As one of the causes of this attenuation, a decrease in the gastric mucus volume was suggested.

Efficacy of sucralfate in the prevention of recurrence of peptic ulcer--double blind multicenter study with cimetidine.

A double blind, multicenter, six-month maintenance study was performed to assess the efficacy and safety of sucralfate (S), cimetidine (C), and their combination (S + C) in the prevention of peptic ulcer recurrence in a six-month observation period. 127 patients with gastric ulcer (GU) (group S: 39, group S + C: 48, group C:40) and 103 patients with duodenal ulcer (DU) (group S: 35, group S + C: 36, group C:32) were available for statistical analysis. Six to 12 months after healing of GU, the cumulative recurrence prevention rates by Kaplan-Meier method were 89.7----80.3% in group S, 97.6----72.6% in group S + C, 84.5----44.6% in group C. In duodenal ulcer they were 75.9----41.9% in group S, 87.8----47.7% in group S + C, 80.8----40.5% in group C. These results indicate that maintenance therapies of S and S + C are effective and safe for the prevention of gastric ulcer recurrence.

[Clinicopathological study of early cancer-like advanced gastric cancer].

We had clinicopathologically studied early cancer-like advanced gastric cancer in relation to peptic ulcer (UI). Early cancer-like advanced cancers with the difficulty to distinguish from early gastric cancer were selected for materials. Result were as followed: 1) Early cancer-like advanced cancers were consisted of 133 lesions, of which 128 lesions (96.2%) had peptic ulcer in cancerous lesion (73 lesions were active stage and 55 lesions were scarring stage). 2) Early cancer-like advanced cancers were 17.0% in all advanced gastric cancers. Proper muscle cancer (in which depth of cancerous invasion is up to proper muscle coat) was more common in early cancer-like advanced cancers than in Borrmann type advanced cancers. 3) Early cancer-like advanced cancers with peptic ulcer showed wide intramucosal cancerous infiltration. Thus, average of maximum diameter was 51.8 mm. 4) Those ulcer were commonly reaching to proper muscle coat or subserosa. Submucosal fibrosis was prominent and scattered proliferation of tumor cells were often seen within fibrosis. 5) Extent of cancerous infiltration in mucosa was more wide than that in submucosa. The above findings have led us to consider that early cancer-like advanced cancers have grown because of high degree submucosal fibrosis by the deep ulcerations due to "malignant cycle".

[Study on the usefulness of haptoglobin used on endoscopic injection sclerotherapy].

The effect of haptoglobin (Hp) used on endoscopic injection sclerotherapy (EIS) was evaluated by examining the increase of serum free hemoglobin (FHb) and the changes of renal function. In control group, the increase of serum FHb (delta FHb) was paralleled with the volume of 5% ethanolamine Oleate (EO) injected intravariceally, and free Hp (FHp) was disappered in this group soon after EIS. On the contrary, in the group treated with Hp, neither the increase of FHb nor decrease of FHp were recognized. The significant increase of urine beta 2 microglobulin and NAG was recognized in control group. Therefore, if Hp is used at initial EIS, it would be prevented that serum FHb due to intravascular hemolysis increases, consequently the possibility of renal dysfunction.