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Biomedical subjects

T Yamane

Publications and source records attributed to T Yamane.

At least 19 recordsLinked to original sources

Identification of Ca2+/calmodulin-dependent protein kinase and endogenous substrate of Fusarium oxysporum.

Ca2+/calmodulin-dependent phosphorylation and cross-reactivity between anti-rat brain Ca2+/calmodulin-dependent protein kinase II (CaMK) antibody and partially purified CaMK from Fusarium oxysporum were detected in the component of high-molecular mass (M(r) greater than 100,000). In vitro, Ca2+/CaM-dependent phosphorylation of only a 16-kDa protein was detected. The 16-kDa protein was localized in the membrane fraction. Amino acid sequence of one of the peptides derived from partial hydrolysis of the 16-kDa protein had a high homology (65.5%) with the bovine transducin beta chain. It is assumed that the 16-kDa protein is an endogenous substrate of F. oxysporum CaMK.

Amino Acid Sequence

Gallbladder mucosa ornithine decarboxylase activity is increased in patients with anomalous arrangement of the pancreaticobiliary duct.

Ornithine decarboxylase (ODC) activity, which seems to increase in premalignant lesions, was studied in gallbladder mucosa from 32 patients with or without anomalous arrangement of the pancreaticobiliary duct (AAPBD). Mucosal ODC activity was significantly increased in 17 patients with AAPBD compared with 15 control subjects with normal biliary anatomy. Among the 17 patients with AAPBD, ODC activity was significantly increased in 7 in whom the major pancreatic duct joined the common bile duct (P-C type) compared with 8 in whom the common bile duct joined the pancreatic duct (C-P type). The increased ODC activity in gallbladder mucosa suggests that patients with the P-C type of AAPBD may have an increased risk of gallbladder cancer. These results are consistent with recent clinicopathologic studies of AAPBD that have demonstrated an association between AAPBD and biliary tract malignancy. Determination of the mechanism that induces mucosal ODC activity may provide a clue to the pathogenesis of gallbladder carcinoma in patients with AAPBD.

Adult

Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer.

Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful, largely because the drugs are not retained in the peritoneal cavity. We have assessed the prophylactic efficacy of a delayed-release preparation--mitomycin adsorbed onto activated charcoal (M-CH). 50 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with M-CH (50 mg mitomycin intraoperatively) or no anticancer prophylaxis (control). Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients (1 was lost to follow-up) than among the 25 controls (p less than 0.01). There were significant differences in survival between the groups at 1.5 years after randomisation (difference 34.6% [95% confidence interval 8.5-60.8%]; p less than 0.01) and at 2.0, 2.5, and 3.0 years (41.7% [14.2-69.1%]; p less than 0.005). The concentration of mitomycin was significantly higher in peritoneal exudate than in plasma for 24 h after drug administration. Side-effects were slight and well tolerated. Thus, peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer, presumably by a prophylactic effect on peritoneal recurrence.

Adsorption

In vitro and in vivo activities of KRM-1648, a newly synthesized benzoxazinorifamycin, against Mycobacterium marinum.

The in vitro and in vivo activities of KRM-1648, one of the newly synthesized benzoxazinorifamycins, against M. marinum were compared with those of rifampin. The MIC values of KRM-1648 determined by the agar dilution method on 7H11 medium against 10 strains of M. marinum were 32-128 times and even more below those of rifampin. In an in vivo experiment, KRM-1648 was markedly effective in terms of the incidence of gross skin lesions and the number of CFUs in the lungs and spleen. Its efficacy was much greater than that of rifampin.

Animals

The effects of hyperthermia on the spinal cord.

This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function.

Animals

Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.

Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N-256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.

Acquired Immunodeficiency Syndrome

Palm carotene inhibits tumor-promoting activity of bile acids and intestinal carcinogenesis.

The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly.

9,10-Dimethyl-1,2-benzanthracene

Synthesis and biological activity of 5'-aminobenzoxazinorifamycin derivatives.

Benzoxazinorifamycin reacted with various secondary amines to yield various 5'-substituted aminobenzoxazinorifamycin derivatives. The derivatives exhibited potent activities against gram-positive bacteria and mycobacteria. The antimicrobial activities of these compounds against Mycobacterium tuberculosis and Mycobacterium intracellulare were superior to those of rifampicin. Some of these compounds showed good plasma levels after oral administration in rats.

Animals

Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.

Adult

[Evaluation of clinical features, cytopathological findings and prognosis of histiocyte proliferative disorders].

Clinicopathological analysis was performed in 19 patients diagnosed clinically with malignant histiocytosis. Ultimately, 9 patients died and 10 are still alive. All 19 had fever of unknown origin. Among the 10 surviving patients, 6 recovered with only supportive therapy such as antibiotic treatment. One recovered with steroid therapy and 2 with VP (vincristine and prednisolone) therapy. Complications due to immunodeficiency were detected in one surviving patient and 2 who died. All 9 patients who died had anemia, and 8 had thrombocytopenia. However, among survivors, only one had anemia and only 2 had thrombocytopenia. Chromosomal abnormality was detected in one patient who died. Histiocytic cells were classified morphologically into 3 types: immature, intermediate and mature. In 4 patients who died, histiocytic cells were immature, but in 4 others mature histiocytic cells were detected. In 5 of the 10 surviving patients, histiocytic cells were of the immature type. Immuno-histochemical analysis of the origin of histiocytic cells in 8 deceased patients showed T-zone histiocytes in one, T cells in one, monocyte phagocytic system (MPS) in 5, and histiocytes of unknown origin in one. Thus, malignant histiocytosis is a heterogenous entity including reactive histiocytic disorder, lymphocytic neoplasm and true histiocytic neoplasm. In histiocyte proliferative disorders, red blood cell counts and platelet counts are useful for assessing prognosis, while cytological findings only confuse this evaluation.

Adult

[Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Adult

Enhancement of cytotoxicity in mouse regional lymph nodes by local tissue injection of aclacinomycin A.

The effect of local tissue injection of activated carbon particle adsorbing aclacinomycin A (ACR-CH) on the cytotoxicity in popliteal, inguinal, paraaortic, and axillary lymph nodes was investigated in mice. Aclacinomycin (0.2 mg/kg), a potent antineoplastic drug was injected subcutaneously into the footpad of mice in the form of ACR-CH or as an ACR solution. After a single injection of ACR-CH, the regional nodal cytotoxic response against mouse YAC-1 lymphoma cells was markedly increased and sustained for 7-10 days. The immune response was also increased after ACR solution but to a much lesser extent. These effects were found in popliteal, inguinal, and paraaortic lymph nodal effector cells but not in the more remote axillary nodes. Absorption of adherence cells largely abrogated the cytotoxic response. These results suggest that ACR-CH did not impair but rather stimulated nodal immunoregulatory cells. Potentially ACR-CH may enhance immune responsiveness of regional lymph nodes after subcutaneous administration while concomitantly curtailing neoplastic growth in these same lymph nodes.

Aclarubicin

Bactericidal action at low doses of a new rifamycin derivative, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl) benzoxazinorifamycin (KRM-1648) on Mycobacterium leprae inoculated into footpads of nude mice.

Among a series of newly-synthesized benzoxazinorifamycins, 2 of the 3'-hydroxy-5'-(4-alkyl-1-piperazinyl) derivatives, named KRM-1648 and KRM-2312, whose respective alkyl residues are isobutyl and isopropyl, were examined for efficacy against nude mouse-model leprosy. KRM-1648 completely inhibited the growth of leprosy bacilli inoculated into nude mouse footpads, even 6 months after the medication had been stopped, when given orally at a daily dose of 0.6 mg/kg, 5 or 6 times weekly, during 3-5 months postinoculation. In comparison, the growth inhibition by KRM-2312 was incomplete under the same conditions, though it was still stronger than that by rifampicin. Complete growth inhibition by KRM-1648 was also observed when it was given orally at a dose of 1 or 3 mg/kg twice weekly during the same period. In contrast, the growth inhibition by rifampicin was only slight at 1 mg/kg and partial at 3 mg/kg under the same condition.

Animals

[Clinical evaluation of panipenem/betamipron in severe infections complicating hematological disorders].

Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found.

Adult

Anastomotic stricture with the EEA stapler after colorectal operation in the dog.

Anastomosis of the gastrointestinal tract has been made more secure by the use of the EEA (U. S. Surgical Corp.) stapler. The development of anastomotic strictures after stapling anastomosis is one of the major postoperative complications of this method. This study was done to compare the incidence of anastomotic stricture between stapling anastomosis and layer-to-layer handsewn anastomosis. Twelve dogs were divided into two groups. In each group, two colonic anastomoses were performed. Intestinal contents were not allowed to pass through one of the anastomotic sites created in an isolated segment of the colon, but were allowed to pass through the other site in the remaining colon. By the 28th postoperative day, anastomoses made with the EEA stapler, which had been excluded from contact with feces, had developed significantly more strictures when compared with the other anastomoses (p less than 0.05). The anastomotic strictures were membranous in nature when examined macroscopically and histologically.

Anastomosis, Surgical

Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy.

The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy.

Adenocarcinoma