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Biomedical subjects

T Masaoka

Publications and source records attributed to T Masaoka.

At least 19 recordsLinked to original sources

The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit model.

In this study, we determined the effect of 80% deacetylated chitin (DAC-80) membrane on postsurgical bleeding after visceral and parietal peritoneal abrasion. Japanese white rabbits underwent a midline laparotomy followed either by a bilateral peritoneal sidewall abrasion (4 x 4 cm) or an abrasion of liver surface (3 x 2 cm). The injured surface was then covered with a 0.2 mm thick DAC-80 membrane. On postsurgical day 2, the rabbits were sacrificed and the amounts of postsurgical bleeding was determined by quantitating the number of red blood cells recovered in 50 ml peritoneal lavage fluid. The DAC-80 membrane was found to reduce postsurgical bleeding after the abrasion of liver surface (treated with DAC-80 membrane: 2.9 +/- 0.8; control: 24.6 +/- 5.9 x 10(8) cells/peritoneal cavity, P less than 0.005). This same hemostatic activity was not observed after application in the peritoneal sidewall abrasion model. We also measured plasminogen activator activity (PA) and urokinase inhibitory (PAI) activity in the spent culture media of macrophages recovered from the postsurgical peritoneal exudate. The DAC-80 membrane reduced the PA secretion from postsurgical macrophages after liver surface abrasion (treated with DAC-80: 2.8 +/- 0.7; control: 3.9 +/- 0.9 mPU/ml). The DAC-80 membrane also showed similar effects on PA secretion after peritoneal sidewall abrasion. No significant effects were found in the secretion of PAI by postsurgical macrophages in both surgical models. These findings suggest that the DAC-80 membrane may have hemostatic activity through the modulation of fibrinolytic activity of peritoneal exudative macrophages.

Adolescent

Rare point mutation at codon 301 and 969 of FMS/M-CSF receptor in acute myelomonocytic and monocytic leukemia.

We have investigated whether point mutations occurred at codon 301 or 969 of FMS (M-CSF receptor) in 19 patients with acute myelomonocytic (M4) and monocytic leukemia (M5). Nineteen peripheral blood and bone marrow blood samples collected from M4 and M5 patients were examined by using polymerase chain reaction and hybridization to allele specific oligonucleotide probes. Mutations at codon 301 and 969 of FMS were not detected in any samples. FMS gene mutations at codon 301 and 969 were rarely involved in M4 and M5 patients in Japan.

Amino Acid Sequence

Levels of complement regulatory proteins, CD35 (CR1), CD46 (MCP) and CD55 (DAF) in human haematological malignancies.

Levels of the membrane complement regulatory proteins, C3b/C4b receptor (CR1, CD35), membrane cofactor protein (MCP, CD46), and decay-accelerating factor (DAF, CD55), expressed on cells from patients with haematological malignancies and normal subjects were assessed by flowcytometry using the respective monoclonal antibodies (mAbs). All myeloid and most lymphoid leukaemia samples tested were CR1-negative: two of the 42 leukaemia samples expressed minute amounts of CR1. Lack of CR1 in leukaemia cells was confirmed with two mAbs raised against CR1, 31R, and 243R, which recognized different epitopes and induced different degrees of CR1-mediated fluorescent shift on flow-cytometry in granulocytes and erythrocytes. MCP was increased in most chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL), and was also increased in majority of acute nonlymphocytic leukaemia (ANLL), acute lymphocytic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). Levels of DAF were also high in CML and CLL, and were variable in other types of leukaemia: some were DAF-negative while others expressed extremely high levels of DAF. In CML patients, the high level of MCP and the lack of CR1 were normalized after medical treatment. These results are in agreement with the data obtained with human leukaemia cell lines, and support the hypothesis that CR1 is essentially a differentiated cell antigen and that a high level of MCP reflects some malignant transformation or an immature stage in blood cells.

Antibodies, Monoclonal

Marked increase of CD57+CD16- cells in long-term survivors of graft-versus-host disease after allogeneic bone marrow transplantation.

We have evaluated long-term serial changes in the immunological state from soon after allogeneic bone marrow transplantation (BMT) In 44, mainly leukemia patients with respect to changes in lymphocyte surface markers. Absolute numbers of cluster designation (CD)2+, CD20+ and human lymphocyte antigen-DR+ (HLA-DR+) cells recovered to within their normal ranges three months, one year and two years, respectively, after BMT. The reversal of the CD4+: CD8+ ratio persisted for five years or more but returned to normal after six years. CD57+CD16- cells were markedly increased from three mo up to a maximum of five years after transplantation; they were increased between three and six months after transplantation irrespective of graft-versus-host disease (GVHD), but changes after one year or more differed among patients without GVHD, with acute GVHD, with acute and chronic GVHD or with chronic GVHD. Absolute numbers of CD57+CD16- cells tended gradually to return to normal after one year or more in the group without GVHD but only after six years in patients in the other three GVHD groups.

Adolescent

[Clinical effects of cefodizime in severe infections complicated with hematological diseases. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.

Adolescent

[Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.

Adolescent

[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Adolescent

Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections.

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.

Animals

Keratoacanthoma ensuing from bone marrow transplantation for chronic myeloid leukemia.

We encountered a 36-year-old woman, who developed two keratoacanthomas at rather a short interval after bone marrow transplantation for chronic myeloid leukemia. This skin disease seems to be associated with various factors, but its etiology still remains obscure. The fact that the patient was under postoperative immunosuppressive treatment suggests that, among other factors, a deterioration or an impairment of immunocapacity may play some role in the pathogenesis of keratoacanthoma. It is intriguing that two lesions appeared successively in one patient.

Adult

[Late phase II study of MST-16 (sobuzoxane) efficacy for malignant lymphoma].

A late phase II study with MST-16 for malignant lymphoma was performed with the collaboration of 11 institutions belonging to the Hanshin Hematological Disease Treatment Research Group. Out of a total 40 patients entered into the study, 37 cases (33 of NHL and 4 HD) were evaluated for efficacy and 27 cases for side effects. The response rate was 29.7% (2 cases of CR and 9 PR). The factors affecting response rate were histological classification, phenotype of tumor cell surface and stage of disease. Bone marrow suppression and G-I disorders were the main toxicities observed, but they disappeared by the cessation of MST-16 treatment.

Adult

[Co-operative on salvage chemotherapy with VP-16 for malignant lymphoma. Hanshin Study Group on Treatment for Hematological Disorders].

Forty one patients with refractory malignant lymphoma were treated with a combination of VP-16, ACM, BH-AC, MTX and PDN as a salvage chemotherapy. These patients were either resistant to frontline therapy or refractory in their relapses. Three patients (7%) achieved a complete remission and 14 patients (34%) attained a partial remission. An overall response rate was 41%. Major toxicities were myelosuppression, nausea, and vomiting. However, they were well tolerated. This regimen has been effective in the treatment for the patients with refractory malignant lymphoma.

Aclarubicin

[Minor thoracotomy for the treatment of spontaneous pneumothorax].

We have recently established the following therapeutic principles for spontaneous pneumothorax, and have obtained favorable results. 1. All patients, including those with a first episode, are subjected to thoracotomy. 2. The standard technique is minor thoracotomy through a skin incision of 5 cm which is aesthetically superior, except complicated cases with chronic obstructive lung disease in elderly patients or giant bullae. 3. Bilateral simultaneous axillary minor thoracotomy is applied to bilateral pneumothorax, whether synchronous or metachronous. 4. Thoracotomy is attempted by other approaches when we preoperatively suspect pulmonary bullae in the lung bases or diaphragm. In the past three years (1988 to 1990), 68 out of 70 cases (97.1%) of spontaneous pneumothorax admitted to our department were operated on. Of them, 55 cases (81% of all surgical cases) underwent minor thoracotomy. Pleural abrasion was performed in order to prevent postoperative recurrence of the pneumothorax. The 55 cases of minor thoracotomy consisted of 51 males and 4 females aged 27.6 years on average (range: 15 to 64). In 22 cases (40%), this was the first occurrence, combination with hemothorax was seen in 4 cases, and bilateral simultaneous axillary minor thoracotomy was performed in 11 cases (20%). The location of the bullae was the upper lobe (or upper segment) in 95.5%, the middle lobe (or lingula) in 6%, and the lower lobe (S6) in 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

[A pharmacokinetic study of idarubicin hydrochloride, a new anthracycline anti-tumor drug, in patients with acute leukemia. Idarubicin Study Group].

In 21 patients with acute leukemia, idarubicin hydrochloride, a new anthracycline antitumor drug, was administered i.v. for 3 consecutive days to study the pharmacokinetics. The terminal half-lives (t1/2) of the drug in these patients were 6.40-15.10 hrs. in plasma, and 8.09-16.34 hrs. in blood cells. Its main metabolite idarubicinol remained longer in blood; t1/2 values were 43.46-51.01 hrs. in plasma and 36.61-54.70 hrs. in blood cells. After 2-4 hrs, the concentrations of idarubicinol in both plasma and blood cells exceeded those of idarubicin. The AUCs of idarubicinol in plasma were 5.16-8.36 times higher than those of idarubicin, and AUCs of idarubicinol in blood cells were 2.05-4.57 times higher than those of idarubicin. Among the doses ranged from 5 to 15 mg/m2/day, the AUCs of both idarubicin and idarubicinol increased dose-dependently. In 2-compartment multiple dose models, plasma t1/2 alpha and t1/2 beta of idarubicin were 0.25 +/- 0.13 hrs. and 9.4 +/- 3.4 hrs., respectively. The steady-state volume of distribution (Vdss) was 934.9 +/- 370.7 l/m2, and the plasma clearance was 82.3 +/- 29.7 l/hr/m2. The urinary excretion of the drug was comparatively low. Until 7 days after administration, the mean cumulative urinary recovery rates of idarubicin and idarubicinol were 2.04% and 11.53%, respectively, and 13.57% in total.

Acute Disease

Subacute toxicity of paraquat in beagle dogs: clinicopathology and pathologic examinations.

Beagle dogs were allocated to 4 groups, each consisting of 3 males and 3 females, which received 0.055, 0.165 or 0.495 mg paraquat (PQ)/kg/day sc for 4 w to investigate subacute toxicity. Recovery 4 and 8 w postadministration was studied. In the early stage there was vomiting, decreased activity and undernourishment. Induration and ulcers at the injection sites were seen. The group receiving 0.495 mg PQ/kg had reduced food ingestion and occasional decreases in water consumption until the end of the 4-w injection period. Three animals in the 0.495 mg PQ/kg group were sacrificed in the moribund stage with marked decreases in body weight. Ophthalmologic examination at 4 w of recovery detected hemorrhage around the nasalis vein of the left fundus in 1 animal that received 0.495 mg PQ/kg. No abnormal changes in electrocardiography (ECG) were noted throughout the experimental period. Slightly increased urinary protein, reticulocyte counts, and fibrinogen were observed in a few animals in each group. A few animals that received 0.165 or 0.495 mg PQ/kg had increased phospholipid, blood urea nitrogen, and creatine phosphokinase. The lungs of the moribundly sacrificed animals had moderate atelectasis, localized atelectasis, moderate thickening of alveolar wall and pleura, proliferation of fibroblast-like cells, and abundant fibers in interstitium and alveoli. In the liver there was slight hemorrhage along the gallbladder. On electron microscopy of the lung, proliferation of fibroblasts, myofibroblasts and type II alveolar cells, and some mast cells were observed in thickened alveolar walls. Abundant collagen fibers, destroyed cell debris and mitotic figures of spindle-shaped fibroblasts were also observed in the dilated interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals