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To determine whether a relationship exists between DNA ploidy and the prognosis of hepatocellular carcinoma (HCC), flow cytometric DNA analysis was performed in paraffin-embedded specimens obtained from 44 patients with HCC who underwent hepatectomy. There were 26 diploid (59%) and 18 aneuploid (41%) tumors. No correlation was shown between DNA ploidy pattern and patient age, sex, liver cirrhosis, hepatitis B virus antigen and serum alpha-fetoprotein level. The ploidy pattern had no significant correlation with the presence of vascular invasion or intrahepatic metastasis. Only Edmondson's grade was well correlated with the ploidy pattern. We noted a significant correlation between survival rates and the presence of vascular invasion or intrahepatic metastasis (p < 0.05). In contrast, no significant correlation was found between DNA ploidy pattern and the prognosis of HCC. The results of this study indicate that DNA ploidy pattern may not be a useful indicator for the prognosis of HCCs after hepatic resection, unlike the results of gastric and colon cancers.

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.

In order to clarify the mechanism of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membrane (GBM) in patients with diabetic nephropathy were examined by electron microscopy using our newly devised "tissue negative staining method". The normal human GBM showed a fine meshwork structure consisting of fibrils forming the small pores. The diameter of these pores was slightly smaller than that of human albumin molecules. The GBM in patients with diabetic nephropathy showed irregular thickening. At higher magnification, hitherto unknown cavities and tunnel structures, which were not seen in normal controls, were observed in the thickened GBM. In some portions, these cavities presented a honeycomb-like appearance. The diameters of the cavities and tunnels were far larger than the dimensions of albumin molecules. These enlarged structures are believed to allow serum protein molecules to pass through the GBM from the capillary lumen to the urinary space. These results suggest that the cause of massive proteinuria in diabetic nephropathy is the disruption of the size barrier of the GBM.

The neural cell adhesion molecule (NCAM) is a family of cell surface sialoglycoproteins mediating homotypic and heterotypic cell-cell adhesion. In tumors, NCAM is supposed to be involved with the malignant features characterized by invasive growth and metastasis. In the present study, we evaluated the correlation between NCAM expression of tumors obtained from small cell lung cancer (SCLC) patients and the clinical outcome. NCAM expression was determined semi-quantitatively by an immunogold-silver staining method using the SCLC cluster 1 monoclonal antibody NCC-LU-243. Of 20 SCLC patients studied, six patients with tumors with high NCAM expression had a poor response to chemotherapy, and a short disease-free (p = 0.011) and overall (p = 0.003) survival as compared with 14 patients having tumors with low NCAM expression. These findings indicate that the therapeutic outcome of SCLC may be partly predicted by determining the NCAM expression of the tumor.

We report a preliminary study to determine whether MDR1 gene expression level in small cell lung cancer (SCLC) tumors is a useful predictor of tumor response to chemotherapy and patient survival in association with myc amplification in the tumor. We analyzed 18 patients with SCLC receiving adriamycin and etoposide combination chemotherapy between August 1989 and November 1991; 16 males and 2 females, median age of 68 years, and 7 with limited disease and 11 with extensive disease. MDR1 mRNA expression level and myc family gene amplification were simultaneously determined by polymerase chain reaction using transbronchial biopsy specimens which were obtained at diagnosis. Patients with tumors expressing low MDR1 mRNA responded more favorably to chemotherapy than those with tumors expressing high MDRI mRNA, however, the difference in tumor response was statistically not significant (84.6% versus 40%). The overall survival was significantly shorter in the latter than in the former (7.2 months versus 11.7 months; p = 0.023). The survival of the 4 patients with tumor showing myc family gene amplification was almost identical to that of patients with tumors showing no amplification of the gene (8.2 months versus 8.8 months; p = 0.73). Multivariate Cox's regression analysis supports the notion that MDR1 may be a useful independent prognostic factor.

We report here a case of hepatocellular carcinoma (HCC) with multiple lung metastases, which were disappeared by treatment of OK-432. The patient was a 65-year-old man and was diagnosed in 1986 with a small (17 x 11 mm) HCC in the anterior-superior segment of the liver. A part of the right hepatic lobe including the tumor was surgically removed, and transarterial injections of adriamycin (10 mg/week) and subcutaneous injections of OK-432 (10 KE/week) were given. Two and a half years later, recurrence of HCC in the liver and its invasion to vena cava inferior (IVC) were found. OK-432 administration was then stopped and percutaneous ethanol injection therapy (PEIT) was performed 10 times. Six months later, the PEIT was effective and the liver tumor with IVC invasion diminished. However, multiple lung metastases were visible on roentgenograms of the chest, and serum alphafetoprotein (AFP) concentration increased to 50,000 ng/ml. The OK-432 treatment resumed. After 6 months of OK-432 treatment, the multiple lung metastases were disappeared and the serum AFP level decreased to 100 ng/ml. At present, the patient is surviving without any sign of recurrence in either the liver or the lung. The clinical course of this case suggests that OK-432 might have effectively treated lung metastases of HCC, although the exact mechanisms are at present unclear.

The changes in opioid receptors (Op-R) caused by repeated administration of pentazocine and the effect of concomitant clonidine were investigated. Binding of [3H] naloxone was markedly decreased in the absence of Na+, but was increased in the presence of Na+ in the diencephalon-mesencephalon of chronic pentazocine-treated rats. No significant changes were observed in the cerebral cortex of pentazocine-treated rats. The pentazocine-induced changes in Op-R were abolished by the concurrent use of clonidine, an alpha-adrenergic agonist, which has been shown to relieve the withdrawal symptoms of morphine. This result indicated that the behavioral action of clonidine can also be observed at the Op-R level.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).

We report a family whose members have familial spastic paraplegia (FSP) associated with epilepsy. A man and his sister initially had primary generalized epilepsy with tonic-clonic seizures, but they have had no seizures for years. However, they developed spastic paresis of the lower extremities and presently show features of FSP. Their mother seemed to have suffered from FSP. One son of the female patient has epilepsy. The clinical picture of this family suggests a close relationship between FSP and epilepsy.

Serum fucose levels and fucosyl transferase activities have been designated as nonspecific markers of malignancy, and play an important role in the diagnosis of different types of malignancies. In the present study, attempts were made to determine the prognostic significance of these markers in patients with cancer of the uterine cervix after therapy. It was found that both serum fucose and fucosyl transferase, which were elevated in untreated patients declined significantly in patients responsive to therapy at different follow-up intervals, but not in patients unresponsive to therapy.

Free amino acid contents in various guinea pig tissues were determined with an amino acid analyzer. The most abundant amino acids in these tissues were: Gly and Glu in the liver and kidney, Gln, Glu and Ala in the heart, Glu and Gln in the brain, Gly in the blood plasma and Lys in erythrocytes. Glutathione was present as the reduced form in these tissues. Cystine was not detected except in the blood plasma, but cysteine was present in these tissues. These results indicate that most thiols are present in the reduced form in these guinea pig tissues. Taurine contents were low compared with those in rat tissues. The results were discussed in relation to the metabolism of sulfur-containing amino acids, and it was suggested that the oxidative metabolism of L-cysteine was lower in guinea pig tissues than in rat tissues.

Age-related alterations in the host defense system have been vigorously investigated because of increased susceptibility to infection and neoplasms in the aged. Although monocyte-macrophages form a major part of the cellular defense against microorganisms, the majority of investigations has been limited to neutrophils and lymphocytes. The present study, designed to determine the influence of age on mononuclear phagocytes, revealed no significant decrease in the absolute number of blood monocytes, but did reveal a tendency for the chemiluminescence of blood monocytes to decrease (p less than 0.10) and a significant decrease in the numbers of macrophage precursors (p less than 0.05) in the aged (over 70 year old), in comparison with controls (under 40 years old). On the basis of these findings, functional alterations of monocyte-macrophages seem to participate in the increased susceptibility to infection in the aged.

A 76-year old farmer ingested 100 g of chlorphenamidine (Galectron), a plant acaricle, for the purpose of suicide. Gastric lavage was performed and the patient survived. Methemoglobinemia was noted after emergency treatment and was still present at 20 hours after ingestion of the compound. The patient was lethargic for at least 50 hours. Moderate neutrophilic leukocytosis and kidney injury were observed.

Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes.

In order to formulate an early diagnostic method for acute rejection after kidney transplantation, macrophage migration inhibition test (MIT) was carried out with lapse of time after inbred rat kidney allotransplantation. The mean survival time of rat kidney allograft was found to be 7.07 +/- 1.34 days. On the other hand, in the group treated with rabbit anti-rat lymphocyte serum (ALS) the mean survival time was lengthened to 14.15 +/- 2.14 days (p less than 0.05). The corresponding antigen used for MIT was prepared with donor kidney by ultrasonication, and its protein concentration at 180 mug/ml was the most optimal as not to elicit non-specific inhibition of macrophages. In the control group, activity of macrophage inhibitory factor (MIF activity) turned positive 3 days after the transplantation, and it became strongly positive by 5 or 7 dyas at the period when rejection crisis appeared frequently. ALS-treated group showed a lower MIF activity than the control group (p less than 0.05) and on 7-12 dyas before rejection crisis appeared frequently, MIF activity became strongly positive. These findings suggest that this MIT is simple and will be proved to be useful in predicting the acute rejection as well as in controlling the immunosuppression.

A case with prolonged bacterial infection accompanied by an abnormal serum protein which migrated in the post-gamma region on electrophoresis is presented. The abnormal protein was identified as IgG with gamma-type light chain moiety. The patient suffered from prolonged pneumonia and cholecystitis, Bone marrow aspiration and skeletal x-rays did not indicate multiple myeloma.

The macrophage migration inhibition activity [MI activity) was stable in sensitized lymphocyte-to-marcophage ratios of 1:5 to 1:20 in mice. Antigen protein concentrations under 100 mug/ml did not induce nonspecific macrophage migration inhibition. Inhibition of tumor proliferation and survival was observed after a combined injection of BCG and MH-134 cells. After a single injection of MH-134 tumor cells, MI activity was reinforced and prolonged, demonstrating the clear effects of BCG as adjuvant. In DDS mice MI activity was weakened in the regional lymph node after a subcutaneous injection of just above or below 10(5) Ehrlich cancer cells previously treated with mitomycin C. This finding suggests the presence of an optimal tumor antigen concentration.

Neocarzinostain (NCS) was first used by Hiraki and his colleagues for induction chemotherapy in acute leukemia. This new anti-tumor agent is a polypeptide with a high molecular weight of 10,700 daltons. Anti-NCS antibody was produced in rabbits administered NCS intramuscularly with or without adjuvant. The production of anti-NCS antibody in patients treated with NCS was investigated. Forty three leukemia cases of various types were examined totally 65 times. Two mg of NCS for four consecutive days by intravenous drip infusion followed by 7 to 10 days of pause was repeatedly administered. The total amounts ranged 8 to 174 mg and the total periods 4 to 87 days. The methods used to measure the antibody titer are the passive hemagglutination (PHA) test on microplate and the passive cutaneous anaphylaxis (PCA) reaction in guinea pigs. The sera of all patients showed only non-specific agglutination at less than 2(3) dilution by PHA test, and to confirm these results four patient sera were tested by PCA reaction. The production of anti-NCS antibody was not detected in patients by PHA test and PCA reaction. The anaphylactic reaction and other adverse reactions due to anti-NCS adtibody production were not demonstrated in patients. Anti-NCS antibody was not detected by these experiments in the dose schedule administered.

1. Clinical and histological evaluation of so-called chorioepithelioma malignum and hydatidiform mole has been made on the cases treated at the Department of Obstetrics and Gynecology, Okayama University Hospital during the 20year period friom 1939 to 1958. 2. CC has been confirmed to be a poor risk in the treatment than CA and SE. 3. The two-year cure rate and the five-year cure rate yield an approximate value in each of CC, CA and SE, so that the two-year survival would be an ideal index for determination of the prognosis. 4. It may be pointed out that CC would indicate a tendency of a higher gonadotropin content suggestive of the poor prognosis, provided the disease contain a greater number of La-cells comparing to Sy-cells. 5. Metastasis of CA is not so infrequent as has been formerly believed, and there were two cases, which proved to be a typical SE and had metastasis to the vaginal wall. 6. Concerning the last labor preceding the chorioepithelioma, it has been clarified that the disease occurs more frequently following spontaneous abortion rather than after artificial abortion. 7. It is noted that the mole showing a marked proliferation of the trophoblasts entailed CC. However, in order to evaluate a correlation of the histological findings of the mole with chance occurrence of the subsquent CC, further study on the cases is required.

Attempts were made to identify menstrual blood by means of paper electrophoresis with preparation of extracts of menstrual blood isolated under various conditions and mixed with human fibrin. Also similar analyses were conducted with blood aspirated from the median cubital vein of a woman during menstruation as well as from a man as the control, also with extracts of lochial blood from a woman after normal delivery, and of the blood obtained at arrtificial abortion. Animal fibrins (from rabbit, mouse, steer, and guinea pig) were also used to see the lytic action of the bloods. The following are the results of the present experiments. 1. The identification of menstrual blood by means of paper electrophoresis is a simple method in legal medicine and its electrophorogram is an excellent method to offer an evidence of proof for mentrual blood. 2. By this method it is possible to identify the menstrual bloodstain even after the lapse of time as much as 6 months. 3. It is possible to identify even putrefied menstrual bloodstain. 4. In the case where the material stained with menstrual blood is found in water, it is not possible to identify the menstrual blood by this method. 5. When the menstrual blood is heated at 60°C over 30 minutes, it becomes impossible to identify it by this method. 6. In the case of venous blood during menstruation fibrinolytic product can be detected only on the first day of menstruation, but since it appears only in trace, it is easy to differentiate it from menstrual blood. 7. As for lochial blood the fibrinolytic product can be detected only in the blood obtained on the first and second days of puerperium, but the amount being so slight that it can readily be distinguished from menstrual blood. 8. In the case of the blood obtained at artificial abortion fibrinolytic product appears just as much as in the case of menstrual blood, and thus it is impossible to differentiate it from mentrual blood by this method. 9. As for the use of human fibrin it is best to employ it while it isdresh, but the human fibrin up to 6 days old can be used. However, the older is the human fibrin the lesser the fibrinolytic product detectable. 10. In the case using animal fibrins mixed with the extract of menstrual blood some do produce fibrinolytic product in trace, but since there is a danger of also producing the fibrinolytic product-like substance in venous blood, it is advisable not to use animal fibrins.