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Biomedical subjects

T Konno

Publications and source records attributed to T Konno.

At least 271 records · Page 15Linked to original sources

A clinical trial of live attenuated varicella vaccine (Biken) in children with malignant diseases.

The live attenuated varicella vaccine (Biken) derived from the Oka strain was used for immunization of childhood cancer patients in remission but on chemotherapy. Thirty nine patients were immunized without any severe adverse effects but 6 recipients had a small number of vesicles. Seroresponses were observed in 90% of recipients examined. During the follow-up period 6 leukemia recipients were suffered from natural varicella in family or community contacts. No vaccinee developed herpes-zoster during this study period.

Antibodies, Viral↗

Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image.

Highly malignant rabbit tumor (VX-2) was implanted at the periphery of the liver in 63 rabbits. Selective delivery of the anticancer agent copoly(styrenemaleic acid) conjugated to neocarzinostatin (SMANCS), which was dissolved in an oil contrast medium (Lipiodol), was performed by injection via the proper hepatic artery. The anticancer effect was also evaluated by various parameters. By using low-kVp X-ray examination of the resected rabbit liver, Lipiodol was found to distribute throughout the entire liver arterial lumina and was retained there for about 24 hr, but disappeared from the normal liver arterial lumina gradually. However, Lipiodol was retained in the tumor tissue and vessels for at least 7 days, whereas it was undetectable in any other organs. A radioactive analogue of Lipiodol, a chloroiodinated fatty acid, was prepared by using [14C]linoleic acid. This analogue was used in the study of the distribution by low-kVp X-ray examination, Sudan III staining, and autoradiography. Lipiodol remained in the tumor vessels as well as the tumor cells. The use of the radioisotope yielded a quantitative profile of Lipiodol accumulation in tumor tissues; approximately 1000 times more at 15 min and 100 times more at 3 days after the injection than that of most other organs or plasma. Its major excretion route appeared to be through the bile and then the feces. The biological activity of SMANCS was also determined and was found to be significant in both tumor and liver even 7 days after injection. No activity was found in any other organ or tissue. The relatively high biological activity of SMANCS in the nontumorous liver adjacent to the tumor may be the result of continuous drug release from SMANCS-Lipiodol in the tumor tissue. By histological examination, massive tumor necrosis and infiltration of the inflammatory cells were found in the rabbits treated with SMANCS-Lipiodol. In the rabbits treated with Lipiodol alone, necrosis of the tumor was only minimal, and no infiltration of inflammatory cells was observed. Survival periods of the treated rabbits (n = 14) were significantly longer than those of controls (n = 10); 23.1 +/- 5.5 (S.D.) days versus 16.1 +/- 2.9 days (p less than 0.005), respectively, even though only one injection was used for this highly malignant tumor. Mean tumor size for both groups at laparotomy was 163.3 +/- 83.0 sq mm and 160.5 +/- 76.5 sq mm, respectively (not significant).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Tumor selective drug delivery with lipid contrast medium (smancs/lipiodol): sustained antitumor effect, enhanced diagnostic value and quantification of dosage regimen].

A new method for the treatment of solid tumor, in particular, primary and metastatic liver cancer using a hydrophobic-polymer conjugated macromolecular anticancer agent, smancs is described. Smancs was dissolving in a lipid contrast medium, Lipiodol, as an injection into the feeding artery. The marked antitumor effect was observed in both experimental animals and human trials. In the patients with hepatocellular carcinoma, both reductions in tumor size and alpha-feto-protein were observed in 91% of the patients. The survival period of the treated patient with highly advanced stage and inoperable cases was comparable to or better than that of resected cases. No major side effect such as bone marrow suppression or liver toxicity was observed due to selective drug delivery to the tumor. About half of the patients, however, showed a transitory fever (37-39 degrees C) for 1-3 days. The mechanism for such selective tumor targeting of anticancer agent appears to be due to the difference in the vascularity of tumor and normal tissue. Furthermore, we found that lack of lymphatic clearance system in the tumor made the prolonged and selective retention of such lipophilic drug in the tumor tissue possible. Another advantages of this method are found in radiological approaches. Differential diagnosis of primary or metastatic cancer became possible and dosing regimen can be determined since a presence of the contrast medium is restricted to the tumor area and it parallels to that of the drug being dissolved. Insufficiency in X-ray staining indicates a need for subsequent injection. The selective remaining of Lipiodol in the tumor for long period may help follow-up study as well.

Animals↗

Interleukin-2 activated peripheral blood lymphocytes and the correlation of lytic activity and peanut agglutinin receptor expression on malignant cells.

The possibility that the peanut agglutinin (PNA) receptor and/or its co-ordinate structures on the surface of leukaemia cells might be recognized by lectin free crude interleukin-2 (IL-2) activated human peripheral blood lymphocytes (LAK) was investigated. Analysis was undertaken of the correlation between the sensitivity to allogeneic LAK lysis and the proportion of PNA receptor on different fresh malignant cells. The results obtained suggested that PNA receptor detected by rhodamine isothiocyanate labelled PNA binding assay appeared to be well expressed on leukaemia cells which were sensitive targets for LAK. PNA receptor and/or its coordinate structures seemed to provide a 'target' structure for LAK.

Cytotoxicity, Immunologic↗

[Effect of elcatonin on experimental osteoporosis induced by ovariectomy and low calcium diet in beagles].

Effect of elcatonin, a synthesized analogue of eel calcitonin, on experimental osteoporosis in beagles induced by ovariectomy and a low calcium diet was studied. Twelve female beagles, 15-18 months old, were divided equally into 3 groups. The first group of beagles were ovariectomized and then fed a low calcium diet, Ca: 0.08%, (ovariectomy plus low Ca diet group); the second group was subjected to the same procedure and diet plus daily injection of elcatonin, 1.0 u/kg, i.m., (elcatonin group); and the third group was fed a standard diet, Ca: 1.36%, (control group) for 6 months. The undecalcified bone sections from the iliac crest were analyzed using histomorphometric methods following in vivo double labeling with Calcein. In the ovariectomy plus low Ca diet group, there were a decrease in trabecular bone volume and an increase in both resorption and formation surface of the trabeculae compared with the control group. These changes of trabecular bone volume and resorption surface were significantly prevented by daily injection of elcatonin. The increase of formation surface of trabeculae and mineral appositional rate was noted in the elcatonin group in comparison with the ovariectomy plus low Ca diet group. These results suggested that elcatonin could prevent bone loss caused by deficiency of sex hormone and dietary calcium.

Alkaline Phosphatase↗

Studies on anticancer treatment with an oily anticancer drug injected into the ligated feeding hepatic artery for liver cancer.

In six adult patients with nonresectable liver cancer, as well as in mature New Zealand white rabbits with implanted VX2 carcinoma in the liver, the artery feeding the hepatic lobe with the malignant lesion was ligated, and an oily contrast medium (Lipiodol Ultra-Fluid) was injected into the hepatoproximal lumen of the ligated artery of the liver with carcinoma. The oily contrast medium was detected in all the branches of the artery injected, and thereafter was found only in tumor tissue for 7 days experimentally and for 16 months clinically. Taking advantage of this phenomenon, the therapeutic effect of the injection of an oily anticancer drug (bleomycin oil suspension) into the hepatoproximal lumen of the ligated hepatic artery was investigated in rabbits with VX2 carcinoma of the liver. The mean concentration level of bleomycin in the tumor tissue was 2.4 +/- 0.4 microgram/g 1 week after the injection of bleomycin oil suspension (1.5 mg potency/kg) in three rabbits. However, its concentration level in nontumorous tissue of the liver was undetectably low in two rabbits, but 0.6 microgram/g in the third rabbit. The group of rabbits receiving an injection of bleomycin oil suspension into the ligated artery had a significantly longer mean survival time than those of the experimental group receiving an injection of saline solution of bleomycin into the ligated artery as well as the three other groups treated (P less than 0.02, N = 5 for each group). It may be concluded that an oily anticancer drug injected into the hepatoproximal lumen of the ligated hepatic artery can intensify the anticancer effects of a ligation of the hepatic artery for liver cancer.

Animals↗

Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report.

A clinical evaluation of arterial infusion of high-molecular-weight antitumor agent SMANCS dissolved in lipid lymphographic agent (thiodol) in 44 patients with mostly unresectable hepatoma is described. The treatment regimen demonstrated significant merits both therapeutically and diagnostically. Marked antitumor effects were shown in the decreased serum alpha-fetoprotein levels (86% of cases) and tumor size (95% of cases), and in survival period and histological findings. Furthermore, there was increased diagnostic sensitivity using CT scan, plain X-rays or ultrasound. The procedure of selective arterial administration of 3-4 mg of SMANCS in 3-4 ml of ethiodol per dose was simple to perform and was required only once every 3-4 weeks. Both ethiodol and the drug accumulated more selectively in tumor than in any other tissues and their activity remained for more than 3 weeks. Only minimal side-effects were associated with SMANCS and ethiodol during this study.

Adult↗

Influence of temperature and relative humidity on human rotavirus infection in Japan.

A climatologic analysis of human rotavirus infection in inpatients with acute diarrhea was conducted over a seven-year period. The infection frequency appeared to be related to temperature, but not to relative humidity. Human rotavirus infection was found to appear abruptly when the mean temperature of any 10-day period became less than 5 C (November or December), reached a peak when it was less than 0 C (January and February), and waned when it became greater than 20 C (June and July) in the city of Yamagata in northern Japan.

Adolescent↗

Biliary lipid compositions in cholestatic diseases of infancy.

Biliary lipid compositions in infants with cholestasis were analysed. Bile acid and phospholipid values were appreciably lower in infants with idiopathic neonatal hepatitis syndrome or corrected biliary atresia than in control infants. Cholesterol values were not, however, notably lower in infants with cholestasis. When biliary lipid components were determined in terms of molar percent, bile acid values were considerably lower in infants with cholestasis than in controls, and cholesterol and phospholipids were appreciably higher, as was the lithogenic index.

Age Factors↗

Ultrastructural alterations of Paneth cells in infants associated with gastrointestinal symptoms.

Paneth cells containing abundant and large inclusion bodies found in patients with acrodermatitis enteropathica have been considered as a consistent and characteristic abnormality of this disease. We examined 34 children with gastrointestinal symptoms due to a wide variety of basic diseases and found similar abnormal Paneth cells in most of them, particularly in infants under the age of one year. This abnormality, according to our findings, is attributed to the secondary effect of zinc deficiency due to malnutrition.

Acrodermatitis↗

Epstein-Barr virus-induced precursor B cell lines from patients with congenital agammaglobulinemia.

We have established lymphoid cell lines with diversity of immunoglobulin expression by infection of bone marrow cells of four patients with congenital agammaglobulinemia with Epstein-Barr virus. Immunofluorescent study revealed that the cells of many of these lymphoid cell lines had characteristics of possible precursor B cells, permitting classification as follows: 1) cell lines without any surface or cytoplasmic immunoglobulins (17/28 lines), 2) cell lines which had only cytoplasmic mu heavy chains (line K4 and O2), 3) cell lines with both mu and delta heavy chains in the cytoplasm (line O6 and M5), 4) cell lines which bore surface mu chains and possessed cytoplasmic mu chains but lacked light chain expression (line S5), 5) cell lines which had surface and cytoplasmic delta and lambda chains, and secreted the immunoglobulins (line K5), and 6) cell lines which had surface IgM and cytoplasmic mu and light chains, and secreted the immunoglobulins (5/28 lines). Biosynthetic studies with 14C-leucine confirmed the patterns of immunoglobulin expression found by immunofluorescent analysis. These cell lines may represent some stages of B cell development and provide useful information on the pathophysiology of congenital agammaglobulinemia.

Agammaglobulinemia↗

Ecto-5'-nucleotidase activities in lymphocytes and B lymphoblastoid cell lines from patients with congenital agammaglobulinemia.

Ecto-5'-nucleotidase (ecto-5'-NT) activity was measured in Epstein-Barr virus (EBV)-induced B lymphoblastoid cell lines (LCL) derived from bone marrow cells and peripheral lymphocytes of four patients with congenital agammaglobulinemia (CAG). In control subjects there was no appreciable difference in the range of ecto-5'-NT activity between immunoglobulin (Ig)-producing B LCL and their peripheral lymphocytes. Though peripheral lymphocytes of the patients showed lower ecto-5'-NT activities than those of control subjects, ecto-5'-NT activities in Ig-producing B LCL from peripheral lymphocytes of the patients fell into the same range as those in B LCL from control subjects. Ecto-5'-NT activities in non-Ig producing precursor B cell lines derived from bone marrow cells of the patients also registered within the range of the enzyme activity of Ig-producing B LCL from control subjects. B LCL from mothers of the patients, who were presumed to be heterozygotes, also had the same range of ecto-5'-NT activity as the control subjects. These results indicate that ecto-5'-NT does not appear to be involved in the pathogenesis of congenital agammaglobulinemia.

Agammaglobulinemia↗

An Epstein-Barr virus-negative B lymphoma cell line (THP-2) from a Burkitt's lymphoma of a Japanese patient.

An Epstein-Barr virus-negative lymphoma cell line, THP-2, was established from a Burkitt's lymphoma taken from a Japanese patient. THP-2 cells grew in single cell suspension with a doubling time of 24 hr; the cells carried surface-bound mu-lambda immunoglobulins and formed rosettes with IgG antibody-coated ox erythrocytes. THP-2 cells expressed B1, common acute lymphoblastic leukemia (ALL) (J5) and Ia-like antigens of their surface as defined by monoclonal antibodies. Epstein-Barr virus-associated nuclear antigen (EBNA) was not detected. The cell line THP-2 has been maintained for over 5 years. Among the markers examined, only common ALL antigen has been present on the cell surface of THP-2 for these 5 years.

Antigens, Viral↗