Predictors of relapse in peptic ulcer.

Four hundred and two patients with peptic ulcer were selected for acute therapy with either pirenzepine (100 mg/day) or cimetidine (800 mg/day) using the envelope method. Those who achieved healing within 3 months (251 patients) were randomized in a double-blind fashion to maintenance therapy with either pirenzepine (75 mg/day) or placebo. In a preliminary study of 163 patients in which a multiple regression life-table method was employed, 4 out of 15 possible predictors were found to have a significant influence on relapse. These were site of ulcer lesions, psychological stress, endoscopic findings at the time of healing of the original ulcers, and acute therapy. Stratified analysis of the evolution of relapse by the Cutler-Ederer life-table method indicated that several other factors also influenced relapse in certain patient subgroups. Most relapses (93.8%) occurred at the same site as, or close to the site of, the original ulcers, indicating that ulcer scars also play a role in relapse.

Effect of glycans of Saccharum officinarum on carbohydrate and lipid metabolism of rats.

A polysaccharide fraction of Saccharum officinarum was tested for its effects on carbohydrate and lipid metabolism in normal rats and those fed a high sugar diet. Feeding with the high sugar diet induced an elevation of serum glucose and significant accumulation of lipid peroxides in the serum and liver. The accumulation of lipid peroxides was inhibited by combined feeding with the polysaccharide fraction. Pathological examination showed that endothelial cell swelling in ascending aorta was found in one third of rats receiving the high sugar diet control but no pathological change was observed in all of the rats concurrently treated with the polysaccharide fraction.

[Clinical preventive medicine in cancer diagnosis--proposal for a new cancer diagnostic system in an aging society].

To enroll a large percentage of the cancer high-risk group and to simultaneously screen for various kinds of cancer, a modified combination assay of tumor markers and risk factors in serum was devised. A pilot study using 5 tumor markers, AFP, CEA, CA19-9, CA125, Dupan-2, as well as 3 risk factors of pepsinogen, PGI, PGII, PGI/II, showed 87.0% sensitivity and 58.8% specificity in 54 patients with various cancers and 163 healthy subjects. Eighty percent of stage I or II cases were detected except for one stage I case of right lung cancer and one stage II case of oral cavity cancer. Field work is now under way to detect various cancers among approximately 1000 inhabitants above 50 years of age in a particular town using 11 tumor markers and 3 risk factors. One hundred fifty three of 967 cases (male 372, female 595) showed various abnormal values and some were examined further as higher risk cases to detect particular cancers suspected from the results of the modified combination assay. At present, 5 PAP positive cases were referred to urological clinic for examination and 3 were confirmed histologically as prostatic cancer. This corresponds to approximately a 0.8% of detection rate which is more than 40 times the prostatic cancer mortality. Other kinds of cancer are still under investigation at various specified clinics. If cancer is not detected in these higher risk cases, they will be followed year to year. Further, the most suspicious cases will be examined at a chromosome or DNA level.(ABSTRACT TRUNCATED AT 250 WORDS)

[Practice of clinical preventive medicine in health care].

Reflecting the successful control of highly virulent and lethal infectious diseases achieved in recent years and also the serious side effects reported sometimes after vaccination even in relatively mild diseases vaccination is now being practiced on an individual base rather than compulsive base for groups. This urges strongly a re-inspection of all clinical entities from the standpoint of clinical preventive medicine. The rapidly developing high aging society we are facing also requests the systematization of clinical preventive medicine to maintain a healthy life as long as possible. In this symposium the health care information such as in radiation exposure in which the cause is clear and easy to be well documented is compared to that in ordinary industrial hazards which have complicated causes in general. As an example of clinical entities to be re-checked from the angle of clinical preventive medicine viral hepatitis is chosen and discussion is followed by prevention of cancer which is now the cause of highest mortality in Japan. In addition, adult health care system such as extensive health examinations is compared with the system of health care for children. Such an approach is expected to contribute to the systematization of clinical preventive medicine which is centered on the individual and not mass prevention in practice.

[Gastrointestinal hormones: recent developments].

Progress in gastrointestinal hormone research has increased our knowledge in peptide hormone biochemistry and gastrointestinal physiology considerably. However, this knowledge has not yet helped our understanding of common gastrointestinal diseases. More specific and reliable methods are needed to prove or to exclude the participation of gastrointestinal peptides in the pathogenesis of gastrointestinal diseases. Peptide hormones are potentially useful as diagnostic and therapeutic modalities in the practice of gastroenterology.

[The field of endocrinology-gastrointestinal hormones: radioimmunoassay and regulation of plasma levels].

Radioimmunoassay is still by far the most reliable tool for the measurement of plasma gastrointestinal hormones. However, various factors in plasma, without proper control, can give rise to erroneous results in radioimmunoassay. It contains 1) proteolytic enzymes which degradation the peptide 2) plasma nonspecific interference 3) cross reaction of various peptides of similar structure 4) molecular species which the antibody recognizes, and so on. We reviewed the mechanism of increase in plasma levels of pancreatic polypeptide (PP) measured by radioimmunoassay. Its secretion in the basal state as well as after meals in normal humans and dogs is governed mainly by vagal cholinergic mechanism. However, bile acid and other gastrointestinal hormones (Insulin and CCK) play a part in the postprandial PP response in experimentally induced diabetic and total biliary diversion dogs. The production of hydrochloric acid or secretin is not requisite for plasma PP response to an ingested meal.

[Detection of drug resistant-genes in cisplatin-resistant colon carcinoma cells by RT-PCR assay. II].

The c-fos, c-Ha-ras and c-myc oncogenes have been proposed to play an important role in DNA synthesis. Expression of c-fos, c-Ha-ras and c-myc genes were compared with the human colon carcinoma cell line HCT8S cells and a subline that was 4.5 resistant to cis-diamminedichloro-platinum (cisplatin). Resistant cells (HCT8DDP) exhibited a 4.0, 2.8 and 1.1 fold in mRNA for these genes when compared with the parent cells by Northern blotting analysis, respectively. The reverse transcription (RT)-PCR method has been demonstrated to quantify a sequence of these oncogenes. This method allowed the detection of gene expression from minimal cells. Thus RT-PCR assay could be an effective device in th early detection of oncogenes to cisplatin-resistance.

[Cancer detection and prevention].

Studies were performed on cancer detection and prevention in the high cancer risk group. To improve the screening method in the diagnosis of unspecified cancer, a modified combination assay was devised using a combination of several tumor markers and adding risk factors of malignancies obtainable from blood samples. Five tumor markers, AFP, CEA, CA 19-9, DUPAN-2 and CA 125 were determined simultaneously in each serum sample obtained from 54 patients with various cancer diseases. A modified combination assay was also examined using the risk factors of malignancies, pepsinogen I/II ratio together with 5 tumor markers. Detection rate was elevated to 68.5% by a combination assay using 5 tumor markers. Detection rate by modified combination assay using the risk factor (pepsinogen I/II ratio) together with 5 tumor markers was further improved to 88.8% without decreasing the specificity. The modified combination assay is easy in practice and expected to contribute in the screening of unspecified cancer diseases.

[Detection of drug resistant-gene in cisplatin-resistant colon carcinoma cells by RT-PCR assay. I].

Expression of the TS and DNA polymerase beta genes as a drug resistant-gene were compared with the human colon carcinoma cell line HCT8S and a subline that was 4.5 fold resistant to cisplatin. Resistant cells (HCT8DDP) exhibited 3.4 fold and 2.5 fold increase in mRNA for both TS and DNA polymerase beta gene when compared with the parent cells by Northern blotting analysis, respectively. The RT (reverse transcription)-PCR (polymerase chain reaction) method has been modified to quantify a sequence of a drug resistance gene. This method exhibited greater sensitivity than conventional methods (Northern blotting analysis), requiring less than 1 fetogram of mRNA from cell lines. The RT-PCR assay could be an effective device in the early detection of resistance to chemotherapy.

[Antistreptolysin O].

Automated analyzers based on the quantitative immunochemical methods have been developed and can allow quantitative measurements of antistreptolysin O concentrations in the clinical laboratories. Automated ASO determinations improve in point of operation, time, effort, precision and accuracy, compared with the usual semiquantitative methods of tube dilution techniques based on the method of Rantz and Randall or some modification thereof, microtitration of the Edward method and agglutination test using latex or other particles. However, confusion and many kinds of problems have been brought about by the rapid development of automated ASO measurements in routine use. The principle quantitative immunochemical measurements of automated ASO determinations are immune agglutination assays, which are nephelometric immunoassay (NIA), latex agglutination photometric immunoassay (LAPIA) and turbidimetric immunoassay (TIA). Principles and methods of these automated immunoassay, reagents, ASO standard serum, automated analyzers, precision and accuracy, the present conditions and problems of automated analysis in the clinical laboratories were discussed in comparison with usual semiquantitative measurements. There was a good correlation between automated immune agglutination assay (NIA, LAPIA and TIA) and the usual semiquantitative assay. However, the quantitative accuracy of automated immune agglutination assay was decreased in the regions of low and high ASO values. Availability, precision and accuracy of ASO measurement were improved by the automated analysis. However, the methods of ASO measurements were increased and varied by the automated assay. Therefore, it is necessary to standardize the automated ASO measurements. The limitation and the clinical significance of the automated immune agglutination assay of ASO have to be studied for practical use in the future.

[Effect of bilirubin on serum fructosamine value, and the elimination of bilirubin by bilirubin oxidase].

Fructosamine is examined as the index of past mean blood glucose levels. However, the fructosamine value appears to be influenced by the bilirubin. Therefore, we examined patients with hyperbilirubinemia showing suspected and definite jaundice. Abnormal fructosamine values were noted in 9 out of the 50 cases (18%) with suspected jaundice and 40 out of the 55 cases (72.2%) with definite jaundice. An experiment in which bilirubin was removed by bilirubin oxidase revealed that fructosamine levels in hyperbilirubinemia correlated with the values of bilirubin and increased fructosamine values were expressed as the values of bilirubin x 6.5. These results demonstrate abnormal fructosamine values not only in jaundice patients but also in those with suspected jaundice. These cases must be taken in the examination of fructosamine in patients with hyperbilirubinemia.

[Clinical evaluation of four tumor markers (CEA, TPA, CA50 and CA72-4) in colorectal cancer].

In a total of 194 cases, consisting of 86 cases of colorectal cancer undergone operation later, 7 cases of non resectable cancer, 34 cases of recurrence, 43 cases of NED (no evidence of a recurrence after radical surgery for colorectal cancer) and 24 cases of benign colorectal disease, serum CEA, TPA, CA50 and CA72-4 levels were determined. The positivity rate was high for all four markers in stage V cases among 86 cases of colorectal cancer, and in cases of non resectable cancer and cases of recurrence. The highest positive rate was obtained with CEA. On the contrary, in cases of stage I to IV the positivity rates of these four tumor markers were as low as 0 to 34.8%. Out of 127 cases of colorectal cancer excluded of 43 NED cases, 52 cases were negative for all four tumor markers and 14 cases were positive only for CEA. In 49 cases, CEA and at least one of the other three tumor markers gave positive results. In 12 cases, CEA gave negative results and at least one of the other three tumor markers positive results. In conclusion, measurement of blood levels of these tumor markers is limited of its usefulness in early diagnosis of colorectal cancer. However, in the diagnosis of advanced stage and of recurrence during the postoperative follow-up period the measurement of tumor markers provides useful information. CEA is most sensitive among the four tumor markers tested and any combination of these four markers is not advantageous because of an increase in false positivity rate.

[Evaluation of hyperlipidemia in high school student--Part 1].

Recently the risk of ischemic heart disease (IHD) is increasing in young generations. Thus, we evaluated the degree of hyperlipidemia in the students of high school in Miyagi prefecture. At first, we examined the plasma level of total cholesterol in all students as screening. About 10% of all the students showed high level of total cholesterol over 200mg/dl. For second screening, we examined further indexes for hyperlipidemia including lipids, glucose and blood pressure at fasting state and got information about family history, diet and exercise. There was positive correlation between total cholesterol and LDL-cholesterol (LDL-C), but no relation was found among others. Lipoprotein (a) which was an independent factor of IHD showed a broad distribution as described before, and had no relation with other lipid levels. Early education and a familial consultation for protecting from IHD should be followed after the screening of lipids levels.

[An evaluation of tumor markers and risk factors in mass screening for various cancers].

The borderline values of tumor markers and the clarification of risk factors for cancer are problems to be solved in the development of mass screening tests for various cancers. A tiny abnormality may be overlooked in an evaluation based upon traditional reference standards obtained by surveying healthy subjects. Both negative and positive values are required in mass screening for various cancers. That is, cut-off values should minimize the incidence of false negatives and false positives in the screening test. A modified combination assay using tumor markers and risk factors was used to screen 967 healthy subjects over age 50 for nonspecific cancers and the results were analyzed. Positive rates based on ordinary cut-off values for each tumor marker were about 6 to 7% in CEA, CA19-9 and BFP, 2.7% in SPAN-1, 1.3% in PAP, and less than 1% in AFP, SCC, CA125 and NCC -ST-439. For pepsinogen, a risk factor of various cancers especially in the digestive tract, the cut-off value was determined as the mean-SD in 967 healthy subjects over 50 years old. That is, the cut-of value for pepsinogen I was 18.7 ng/ml. A lower value was found in 149 subjects (15.4%). The cut-off value for pepsinogen II was 7.4 ng/ml and a lower value was found in 227 subjects (23.5%). The cut-off value for the pepsinogen I/II ratio was 1.2 and 108 subjects showed lower values (11.2%). Positive cases were referred to specialists in various fields to detect the specific suspected cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

[Molecular and immunological approach to hematological disease: detection and analysis of intracellular modified nucleosides by flow cytometry].

Modified nucleosides are components of ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). 1-methyladenosine and pseudouridine are members of those modified nucleosides. The urinary concentration of 1-methyladenosine and pseudouridine of cancer patients are higher than that of healthy controls, and those compounds were reduced after effective chemotherapy. Thus those compounds might be expected to use as tumor markers. In this study cellular origin of 1-methyladenosine and pseudouridine were analysed about two tumor cell lines (HUT-102, THP-1), peripheral blood lymphocytes (PBL) from healthy adult and PBL under the phytohemagglutinin stimulation, by flow cytometric analysis and immunofluorescent staining of cellular RNA using monoclonal antibodies specific for 1-methyladenosine (AMA) and pseudouridine (APU). Both 1-methyladenosine and pseudouridine were detected in more than 90% of tumor cells above the thresholds of flow cytometric detection (Spectrum III, Ortho). The PBL under the PHA stimulation also tended to take the same way of the tumor cell lines, whereas few of the PBL contained 1-methyladenosine above the thresholds. According to the DNA analysis of those cell lines, high contents of the modified nucleosides in the cell might follow DNA synthesis, this leads to one reason for high levels of the urinary excretion of the modified nucleosides in cancer patient.

[Plasma lipid peroxides in the operation of esophageal cancer].

Lipid peroxides are formed by autooxidation of polyunsaturated fatty acids found primarily in cell membranes. An increase level of lipid peroxides in the tissue therefore reflects membrane damage. We reported that water immersion restraint rats caused significant increase of gastric mucosal lipid peroxide which reflected on gastric mucosal injury. The gastric mucosal injury is also known as the post-operative complication due to physical stress. So we studied plasma lipid peroxide and its related substances in the operation of esophageal cancer. Lipid peroxide levels increased significantly in pre- and post-operation but temporal decrease was found during the operation. Vitamin E is thought to be an important structural component of biologic membranes and is believed to act as a free radical scavenger in lipid peroxidation. Vitamin E also increased in the patients of esophageal cancer and decreased significantly during the operation. Superoxide dismutase changed frequently during the operation but there was no deficit tendency in its changes. Catalase levels also changes frequently and showed temporal but statistical elevation after the operation. These results indicated that lipid peroxidation may contribute to the development of organic damage in the operation of esophageal cancer.

[Campylobacter pylori and diseases of the stomach].

In spite of extensive clinical studies the pathogenicity of Campylobacter pylori in various diseases of the stomach is still not fully elucidated. In peptic ulcer Campylobacter pylori has not provided a reasonable explanation for the localized and solitary development of ulcer lesion which is one of characteristic features of this clinical entity. Our previous clinical study revealed that relapse occurs mostly at or near the scar of the preceding ulcer lesion and occurs more often in red scar than in white scar in peptic ulcer. Therefore, the scar was chosen to investigate whether there is a correlation between Campylobacter pylori and relapse. Twenty patients with healed gastric ulcer were biopsied in duplicate at 4 different sites, namely at the center of and near the scar of the preceding ulcer lesion, in the body and pyloric antrum. One of the duplicate specimen was stained, and the other cultured. Number of the colony observed on the plate was highest at the scar center followed by near the scar or in the body, and the pyloric antrum showed the lowest. Campylobacter pylori was detected in 46.7% of red scar, and 20% of white scar. Campylobacter pylori may play a pathogenic role in some patients of peptic ulcer, but not in all. Namely Campylobacter pylori is one of factors which may cause in imbalance between offensive and defensive powers at gastric mucosa and may lead to development of ulcer lesion. In case of positive bacteriological test, therefore, as to presence of Campylobacter pylori, the preventive measure for relapse such as bismuth preparation may be considered.

[Correlation between gastric emptying time and both plasma gastrin and pancreatic polypeptide in streptozotocin diabetic dogs].

Correlation between gastric emptying time and both plasma gastrin and pancreatic polypeptide (PP) levels after meal was studied in 9 normal and 5 streptozotocin (STZ) diabetic dogs. Moreover, the effects of exogenous insulin at doses of 0.2 and 0.4 U/kg on gastric emptying and plasma hormone levels were also studied in STZ diabetic dogs. The time required to reach the peak of plasma acetaminophen level, which is the indirect indicator of gastric emptying rate, was significantly delayed in STZ diabetic dogs than in control dogs. Plasma gastrin response was delayed slightly in STZ diabetic dogs, but the plasma levels were not significantly different between the two groups. Plasma PP levels both in the basal and after postprandial state were significantly higher in STZ dogs than in normal dogs. Infusion of insulin did not affect plasma levels of acetaminophen and gastrin, while it produced a dose-dependent suppression of postprandial PP rise in STZ diabetic dogs. The foregoing data indicate that high level of plasma PP observed in STZ dogs did not correlate with gastric emptying but with insulin deficiency.

[Effect of ursodeoxycholic acid on water immersion restraint stress ulcer of rats].

Ursodeoxycholic acid (UDCA) has been used in the medical treatment of various gastrointestinal diseases. In this study, UDCA-supplemented rats were investigated to elucidate the role of UDCA in the pathogenesis of gastric mucosal lesions induced by water immersion restraint stress. In UDCA-administered rats, the increase of gastric mucosal lipid peroxide (LOP) and ulcer index after 2 hour's stress were prevented as compared with the rats fed on standard diet to serve as the control. In addition, the increase of serum and gastric mucosal catalase after the stress were also suppressed. These results suggested that antioxidant effect of UDCA on the lipid peroxidation may play a role in prevention of gastric lesions induced by water immersion restraint stress.