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Biomedical subjects

I Hashimoto

Publications and source records attributed to I Hashimoto.

At least 145 records · Page 8Linked to original sources

[Effect of anabolic steroid on immune response].

Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

Female

[5-Fluorouracil concentration in various tissues from cancer patients after oral administration of 5-fluorouracil].

5-Fluorouracil(5-FU)is a widely used antitumor agent for treating patients with adenocarcinoma of gastroenterial tract and breast following intravenous or oral administration. The blood level of 5-FU peaked rapidly after intravenous bolus injection and then decreased in a short time, disappearing 90 minutes after injection. But the blood level of 5-FU peaked from 15 to 30 minutes after oral administration of 5-FU tablets or dry syrup and decreased slowly, frequently showing 0.02 microgram/ml at 120 minutes after oral administration. In cancer chemotherapy, a tissue drug concentration is represented by its serum level in practice, generally because of the difficulty in determining the tissue drug level of the patients. This study was performed to determine the tissue 5-FU level after oral administration of 5-FU. Before surgery, 400 to 600 mg of 5-FU tablets was orally administered to 13 patients including 5 cases of gastric, 5 of breast, 1 of colon and 2 of other types of cancer. Tissue specimens of different sites and serum samples were obtained during the operation: cancer tissues, normal gastric or colon wall, normal breast, lymph nodes and subcutaneous fatty tissues, etc. The materials were frozen immediately at -20 degrees C and sent to Pharmaceutical Research Laboratories, Fuji Plant, Kyowa Hakko Kogyo Co., Ltd. ( Nagaizumimachi , Shuntogun , Shizuoka , Japan). The materials were assayed for 5-FU by bioassay method using Staphylococcus aureus 209P or Micrococcus flavus ATCC 10240 as the test organisms. The 5-FU concentration in mastopathy tissue was traced to all of the agents at 20 to 180 minutes after 400 mg of 5-FU was administered orally in tablet form. 5-FU concentrations in gastric cancer tissues ranged from 0.30 to 1.30 micrograms/g at 163 to 235 minutes after administering 600 mg of 5-FU tablets, whereas in normal gastric wall were much lower than in gastric cancer tissues. That in the breast cancer tissues was 0.042 to 0.12 microgram/g at 100 to 240 minutes after oral administration. 5-FU was maintained at a higher concentration in cancer tissues for a long time, while the serum concentration decreased to trace amounts. 5-FU in non-cancerous tissues was invariably traced in most patients as mastopathy tumors. From the above results, 5-FU tablets proved to be a useful drug in cancer chemotherapy.

Adenocarcinoma

Comparative studies on the neurovirulence of temperature-sensitive and temperature-resistant viruses of enterovirus 71 in monkeys.

The neurovirulence of strain BrCr of enterovirus 71 (E71) was compared in monkeys between temperature-sensitive (ts) and temperature-resistant (tr) viruses. Comparisons are made relative to clinical disease, pathologic findings, serum neutralizing antibody titers, CNS virus replication as measured by infectivity titrations and immunofluorescence. Clinically, ts virus did not produce a clinical disease. The tr virus, however, produced paralysis. Pathologically, little or no nerve cell damage was found in the CNS of monkeys inoculated with ts virus, although mild to moderate interstitial changes occurred. In monkeys inoculated with tr virus, marked nerve cell damage and inflammatory reaction were found in the CNS. Serum neutralizing antibody titers in monkeys inoculated with ts virus rose on day 25. No virus was detected in the CNS of monkeys inoculated with ts virus, while a high virus titer was detected in the CNS of monkeys inoculated with tr virus. No specific immunofluorescence was detected in the nerve cells of the CNS in monkeys inoculated with ts virus, but specific fluorescence was detected in the nerve cells of the CNS in monkeys inoculated with tr virus. Virus growth in the CNS correlated well with the severity of clinical and pathologic findings, and immunofluorescent studies. The results show that ts virus was much less neurovirulent than tr virus, indicating that ts virus resembles the attenuated poliovirus which could not grow at a higher temperature. It is inferred that the genetic factors which influence the reproductive capacity of E71 at a higher temperature are very closely correlated with the neurovirulence.

Animals

Spontaneous blastogenesis assay for detection of renal allograft rejection in man.

In attempts to assess the possibility of allograft rejection, serial assays of spontaneous blastogenesis (SB) by uptake of tritium thymidine in 50 microliters whole blood were performed in 72 consecutive renal allograft recipients. Of 79 clinically diagnosed rejection episodes, 65 (82 per cent) had an associated elevation of SB values, and 14 (18 per cent) showed false negative results. In 38 (59 per cent) of 65 episodes in which the elevations of SB values were observed, the elevations preceded the clinical diagnosis by 1-7 days. Although large doses of steroids did not affect the values of SB, false positive elevations which were mainly caused by systemic infections occurred in 12 cases. There was no significant association between severity of rejection crisis and the maximum value of SB in the course. The SB assay requiring only a small amount of blood can be accomplished within 4-5 hours and provides a simple means of assessing and predicting host's immune responsiveness to the histocompatibility antigens.

Graft Rejection

Analysis of data on 170 consecutive patients transplanted with kidneys from living relatives.

Graft survival, mortality, histocompatibility and rehabilitation were studied in 170 consecutive patients receiving kidneys from living relatives. Average follow-up was 5 years and one month with a minimum post-transplant evaluation of 6 months. Overall patient survival was 93 per cent at one year and there was a remarkable decline thereafter. Overall graft survival was 84 per cent at one year, 73 per cent at three, and 67 per cent at five years. Among the 76 patients treated since 1979, both patients and graft survival have improved: 93 per cent and 80 per cent at three years, respectively, because of a decrease in serious complications. Although no correlation was found between HLA-A and B loci matching and graft survival in patients with no mismatch in the HLA-DR locus, there was a significantly higher graft survival. Infection, the leading cause of death especially in the early post-transplant period, has been brought under control. Aseptic necrosis of the femoral head which occurred in 27 (16 per cent) patients proved to be the most difficult problem. The majority of patients are functioning well socially and vocationally and reproductive functions have been restored. Transplantation offers a better quality of life for patients with chronic renal failure, as compared to hemodialysis. The increased procurement of cadaver kidneys must be given attention.

Adolescent

Isolation of a temperature-sensitive strain of enterovirus 71 with reduced neurovirulence for monkeys.

Small- and large-plaque-producing viruses were selected from the enterovirus 71 (E71) prototype, BrCr. The small-plaque virus was a temperature-resistant (tr) strain which could multiply at 39.5 degrees C as well as 35 degrees C. The large-plaque virus was temperature-sensitive (ts) and could not grow at 39.5 degrees C. It was shown that the ts strain was much less neurovirulent for monkeys than the tr strain. Both tr and ts strains reacted with homologous and heterologous antibodies in cross-neutralization tests. While no difference was found between tr and ts strains in the size of virion polypeptides, the VP1 polypeptide could be differentiated by isoelectric focusing. Genomic differences between the two strains were found by oligonucleotide mapping.

Animals

Variation in virulence of Coxsackie virus B3 in the heart of mice, II. Pathological comparison.

Histopathological analysis of the heart in adult mice inoculated with Coxsackie virus B3 (CB3) strains revealed that strain SK-74 isolated from a patient suffering from severe diarrhea and fever produced severe myocarditis but strain T-70 isolated from a healthy child induced no lesion in the hearts of mice tested, and that intensities of myocardial lesions in mice inoculated with strain PMH were higher than those in mice inoculated with prototype strain Nancy. The results support the conclusion in the preceding paper that strain SK-74 is virulent but strain T-70 is avirulent in mice. The results also partially indicated that the virulence of prototype strain Nancy in the heart of mice is enhanced by passages of the strain in the heart of mice. All four strains of CB3 produced lesions in the pancreas although lesions induced by strain T-70 were less marked than those induced by the remaining three strains.

Animals

Variation in virulence of Coxsackie virus B3 in the hearts of mice. I. Comparison of mortality and virus growth in the heart and other organs.

Virulence of Coxsackie virus B3 (CB3) was compared in mice between strain SK-74 isolated from a patient and strain T-70 isolated from a healthy child as well as between prototype strain Nancy and its mouse-passaged derivative strain PMH. Strain SK-74 showed a high mortality (40-80%), while strain T-70 did not induce deaths in mice (mortality: 0%). Strain PMH showed a high mortality (65-85%), but strain Nancy did not cause deaths in the mice. In agreement with the mortality trend, virus titers in the heart and other organs of mice inoculated with strain SK-74 and PMH were higher than those in mice inoculated with T-70 and Nancy strains. Since virus titers in the heart remained higher than those in other organs, the heart was regarded as the main organ in which CB3 could replicate and induce cell degeneration. The present results suggest that a marked variation in virulence in the hearts of mice among CB3 strains occurred and that passage through the hearts of mice enhances the virulence of CB3 in the hearts of mice.

Animals

[Mucohistochemical studies of CEA producing and non-producing stomach cancers].

In this report, 141 patients with gastric cancer were studied histochemically. Tissue CEA was stained by the CEA-PAP method and the gastric cancer was classified into CEA-producing (96 cases, 68.1%) and CEA non-producing gastric cancer (45 cases, 31.9%). Histologically, CEA-producing gastric cancer was well differentiated adenocarcinoma and CEA non-producing gastric cancer was chiefly undifferentiated carcinoma. PAS, pH 2.5 Alcian-blue, High Iron Diamine, Alkaline-PAS, and Concanavalin A paradoxical stain were applied to specimens from each type of gastric carcinoma. Mucosubstances of CEA-producing gastric cancer were positive for A-B, HID, AL-PAS and CPS III-1; those of CEA non-producing gastric cancer were positive for PAS and CPS III-s, but negative for A-B, HID and A1-PAS. These results suggest that CEA-producing gastric cancer arises from intestinal metaplasia of gastric mucosa and that CEA non-producing gastric cancer arises from the gastric mucosa itself.

Adenocarcinoma

[Specific active immunotherapy of murine methylcholanthrene-induced sarcoma using a partially purified soluble tumor specific transplantation antigens].

Immunotherapeutic effects of soluble tumor specific transplantation antigens (TSTA) were studied, Crude 3M KC1 extract of C3H/He methylcholanthrene-induced sarcoma (F tumor) was purified by preparative isoelectric focusing (pIEF). The immunoprotective fraction (Fr. 15, pI 5.7-6.0) possessed about 50 fold greater activity than the crude 3M KC1 extract. Three weekly injections of optimal immunoprotective dose of Fr. 15 retarded the outgrowth of F cells and decreased the outgrowth and tumor incidence of rechallenged inoculation in mice completely resected established 1 cm tumor. Weekly injections of Fr. 15 resulted in decreased local recurrences. This therapeutic effect was immunologically specific. Fr. 15 alone did not show the therapeutic effects on the established tumor, but combined treatment with cyclophosphamide gave the increased survivals. A metastatic variant cell line (F-4) metastasized to the lung spontaneously after the resection of primary subcutaneous tumor. Therapeutic injections of Fr. 15 decreased the rates of spontaneous pulmonary metastasis of F-4. Since cross-immunoprotection tests revealed that F and F-4 share the common TSTA, the therapeutic effect of Fr. 15 upon pulmonary metastases might be due to improved host's specific immunity.

Animals

The role of T lymphocytes in the pathogenesis of Coxsackie virus B3 heart disease.

Myocarditis in athymic BALB/c-nu/nu (nu/nu) mice infected with Coxsackie virus B3 was studied to determine whether inflammatory mononuclear cell infiltration was produced by transfer of spleen cells ob BALB/c-nu/+ (nu/+) mice infected with the same virus. In addition, spleen cells of uninfected nu/+mice were transferred into athymic nu/nu mice infected with Coxsackie virus B3. Athymic nu/nu mice infected with Coxsackie virus B3 after transfer of spleen cells of nu/+ mice infected with the same virus developed marked to moderate myocarditis with inflammatory mononuclear cell infiltration. However, athymic nu/nu mice infected with Coxsackie virus B3 after transfer of spleen cells of uninfected nu/+ mice developed moderate to mild degeneration or necrosis of the muscle fibres, although mild mononuclear cell infiltration was found in only one mouse. The incidence of myocardial lesions of athymic nu/nu mice infected with Coxsackie virus B3 after transfer of infected-spleen cells of nu/+ mice was about the same is that in infected nu/+ mice after transfer of spleen cells of uninfected nu/+ mice. However, degrees in the intensity of the muscular changes and inflammatory mononuclear cell infiltration in the former was significantly greater than that in the latter. The results show, therefore, that Coxsackie virus B3 infection stimulated production of cytotoxic activity in the spleen which was evident on Day 6. From the present results, it is confirmed that myocarditis in mice infected with Coxsackie virus B3 is thymus-dependent, supporting previous investigations.

Animals

[Clinical study of cefmenoxime in acute peritonitis: clinical effect and tissue concentration of cefmenoxime].

A new antibiotic drug of cephalosporin group, with marked resistance of beta-lactamase, cefmenoxime (CMX) for parenteral use was tested in 15 patients with acute peritonitis. CMX in a dose of 500 mg was given intramusculary before the operation, to 8 cases with appendicitis, and 2 cases with intestinal obstruction. In 3 cases with appendicitis and a case with intestinal perforation, CMX in a dose of 500-1,000 mg was given by intravenous injection before or during the operation. And in a case with appendicitis, CMX in a dose of 1 g was given by intravenous drip infusion before the operation. Tissue specimens of different sites or body fluids were taken during the operation and from the removed organs. The materials of purulent ascites were subsequently taken at intervals. Determination of CMX concentration was performed according to cup bioassay method with Proteus mirabilis ATCC 21100 strain. The peak of CMX concentration in purulent ascites of patient with panperitonitis for intestinal perforation was 39.5 microgram/ml at 41 minutes after 1 g intravenous administration. Concentration of CMX in pus in the appendix was 52.5 microgram/ml at 20 minutes after 1 g intravenous administration. In 15 patients with acute peritonitis, 11 patients were given CMX in a dose of 500 mg by intramuscular administration twice a day, and the serious 4 patients were given in a dose of 500 mg to 1 g by intravenous drip infusion twice a day. Clinical response was excellent in 10 cases, good in 5 cases, fair and poor were none.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[Clinical effect of cefmenoxime on cholecystitis; its clinical efficacy and tissue concentration].

A new antibiotic drug of cephalosporin, with marked resistance to beta-lactamase, cefmenoxime (CMX) for parenteral use was used in 14 patients with acute or subacute cholecystitis and cholangitis. CMX was given by intramuscular or intravenous drip infusion at a daily dose of 500 mg to 2 g. Clinical response was excellent in 3 cases, good in 10 cases, fair in 1 case and poor in none. Any clinical adverse effect was not recognized. CMX in a dose of 500 mg was given by intramuscular administration before the operation to 8 patients, and in 7 cases CMX in a dose of 1 g was given by intravenous administration before or during the operation. Tissue specimens of different sites were taken from the removed organs. The materials of A-bile and B-bile were subsequently taken at intervals. CMX concentrations in the A-bile increased after intramuscular injection and reached to peak 2 hours, then declined very slowly. CMX concentrations in the A-bile after intravenous administration reached to peak at 1 hour, then declined very slowly, too. CMX concentration in the B-bile reached to high level of the concentration comparative quickly after intramuscular and intravenous administration, and it was thought to be excreted through the gallbladder wall. CMX concentration in the gallbladder wall was directly proportional to the degree of pathological changes of the inflammation. On the CMX concentration in patients with cholecystitis and cholangitis, the concentration in A-bile, B-bile and gallbladder wall were observed higher than the MIC of CMX for pathogenic Gram-negative bacilli. CMX therefore will be a very useful drug when used for chemotherapy of the infectious diseases of the biliary tract.

Acute Disease

[Clinical evaluation of the method to determine antibiotic concentrations in small amounts of samples].

Concentrations of cefotiam (CTM) in the exudate after abdominal operation were studied. The exudates were collected by 6 mm paper discs and the antibiotic concentrations were determined by the paper disc method using Proteus rettgeri ATCC 9250 as test organism. Comparison between agar well and paper disc assay for CTM in ascites specimens showed good correlation. Two grams of CTM was intravenously given to the patients after abdominal operations. The concentration of CTM in the exudate for 6 hours after injection was 0.4--14.2 micrograms/ml and this value exceeded the antibacterial level of CTM. It is, therefore, concluded that CTM will be effective for the postoperative prophylaxis.

Adult

[Chemotherapy of gastric cancer patients with hepatic metastases].

The effect of post-operative adjuvant chemotherapy on the prognosis of gastric cancer patients with hepatic metastases was evaluated. Forty-two cases were classified into-following four groups: (A) no chemotherapy, (B) short-term chemotherapy (5 g of 5 FU i.v., or 1/2 FM (F') C alone), (C) long-term chemotherapy (1/2 MF (F') C plus 0.6 g of FT-207 per os), (D) long-term chemotherapy (1/2 MF (F') C plus 1.5 g/day of FT-207 per annum). Six, nine, twelve month survival rates of patients in group (D) was significantly higher than group (A). Mean survival time of each group was: (A) 4.7, (B) 5.2, (C) 5.7 and (D) 9.1 months. Correlation between the survival time and the total dose of FT-207 was observed. Total dose of FT-207 in group (D) was 129.3 g and 60.8 g in group (C). These may reflect the results that the rectal administration was more effective than the oral administration of FT-207.

Administration, Oral

[UFT concentration in various tissues from cancer patients].

UFT, an antitumor drug combined of Tegafur 1 and Uracil 4, was administered preoperatively to 23 cancer patients including 11 cases of breast, 8 of gastric, 2 of colon and 2 of other cancers. Tissue specimens of different sites and serum samples were collected during the operation: cancer tissues, normal breast, normal gastric, colon or rectal wall, lymph nodes and subcutaneous fatty tissues, etc., and concentrations of tegafur (FT), 5-fluorouracil (5-FU) and uracil were studied using HCLP or GC-MF methods. In most cases, 5-FU and uracil concentrations detected in cancer tissues from the patients were higher than those found in non cancer sites. FT and 5-FU fractions in cancer tissues were found to be higher than those of the patients receiving only 800 mg of Tegafur fine granules as previously reported. Patients with benign tumor having mastopathy or were reported to show very low 5-FU concentration in tissue which was almost undetectable. From the above results, it has been suggested that UFT is a useful drug in cancer chemotherapy.

Administration, Oral

Genetic counseling for skin diseases. A statistical analysis of 182 cases.

A statistical study was carried out on 182 cases who seeked out genetic counseling about skin diseases. The size of the latent demand for the counseling was assessed to be as much as 3.0% of the outpatients. Most clients were in their twenties. A representative consultand was the patient's child or sibling. The main diseases in question were cleft lip and palate (16%), nevus pigmentosus (12%), Recklinghausen's diseases (8%) and psoriasis (8%). Estimation of the recurrence risk was impossible in 3%, approximate in 54% and accurate in 43%. This defective estimation is due to the insufficiency of the available genetic data, e.g. carrier frequency, penetrance rate, contraction rate by age, etc. The high-risk cases were found to be 36%. In 9 cases (5% of all the counselings) the client decided to avoid reproduction. In 30 cases (16%), the clients asked for counseling after having conceived or given birth to a consultand. They were thought to be too late from the standpoint of prophylaxis of inherited diseases. Our conclusion is that genetic counseling offers some measure of disease prevention and therefore will become an essential branch or dermatology in the future.

Adolescent