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Biomedical subjects

R Kamata

Publications and source records attributed to R Kamata.

At least 37 records · Page 2Linked to original sources

Effects of protease inhibitors on growth of Serratia marcescens and Pseudomonas aeruginosa.

The growth inhibitory effects of chicken egg white ovomacroglobulin (ovoM) on Serratia marcescens and Pseudomonas aeruginosa were studied. The growth of protease-producing strains was greater than that of the strains producing little protease, and was inhibited in a dose-dependent manner by ovoM, a potent protease inhibitor. Dose-dependent enhancement of growth of strains of S. marcescens and P. aeruginosa that produce little protease was observed with the medium treated with proteases. These results indicate that extracellular proteases produced by the organisms augment their growth and that inhibition of the proteases results in suppression of growth.

Gelatin↗

Spreading of Serratia marcescens in experimental keratitis and growth suppression by chicken egg white ovomacroglobulin.

We studied the inhibitory effects of chicken egg white ovomacroglobulin, a broad-spectrum protease inhibitor, and a synthetic protease inhibitory peptide, Bz-GFR-O-mercaptoanilide, on the growth of two strains of Serratia marcescens in a synthetic medium. The growth of the virulent protease-producing strain, S. marcescens kums 3958 (kums 3958), was more rapid than that of the strain producing minimal protease, S. marcescens kums NA (kums NA), and kums 3958 was inhibited in a dose-dependent manner by ovomacroglobulin. The synthetic inhibitor also inhibited the growth of kums 3958 weakly. Dose-dependent enhancement of growth of kums NA was observed in the medium treated with the serratial 56 kilo Dalton protease. By immunohistochemical methods using an antibody to the bacteria, the spreading of kums 3958 was also studied in corneal tissue in experimental keratitis of the guinea pig. In vivo, kums 3958 grew locally, and then spread widely by destroying stromal tissue 7-8 hours after intrastromal injection of the organisms (3 x 10(4) colony-forming units). On the other hand, when kums 3958 mixed with ovomacroglobulin was injected into the cornea, the organisms remained locally in the corneal stroma which showed a lower grade of damage. These results indicate that proteases secreted from S. marcescens destroyed corneal stroma, yielding the organisms enough space for further spreading.

Anilides↗

[Experience of multimodal therapy for advanced neuroblastoma].

The prognosis of advanced neuroblastoma is extremely poor. We treated 5 patients with advanced neuroblastoma, older than 3 years, with multimodal therapy including intraoperative irradiation and autologous bone marrow transplantation. Elevated serum NSE and ferritin level and unfavorable histology according to the Shimadas histological classification, all of which are indicators of poor prognosis, were found in all of them. N-myc oncogene was amplified in 3 cases. After preoperative intensive induction chemotherapy, delayed primary operation and intraoperative irradiation (10-15 Gy) were performed. The postoperative lethal dose chemotherapy and total body irradiation (33 Gy x 3 days) were followed by autologous bone marrow transplantation. Tumor cells were purged using immunomagnetic beads method. Two cases showed recurrence (brain; 1, bone and bone marrow; 1) and a metastatic brain tumor was extirpated completely. All of them are alive during the follow up period from 6mo. to 4y8mo. (mean; 2y5mo.) with no evidence of disease except one. It may be concluded that our multimodal therapy is effective in achieving better results for advanced neuroblastoma.

Bone Marrow Purging↗

[A preliminary study on MR lymphography with iron chondroitin sulfate colloid].

We investigated MR lymphography with iron chondroitin sulfate colloid, which was an intravenous agent for iron deficiency anemia. MR images (SE350/30) of the medial iliac lymph nodes were obtained before and after subcutaneous++ injection of this agent (2 mg Fe) on dorsal hindfeet bilaterally in five rabbits (3.0 kg weight). Signal intensities of the nodes were increased 5-15 minutes after the injection and the nodes were clearly identified in three of them. In the other two, increase in the signal intensity was not shown and any nodes could not be detected macroscopically at the investigated region on dissection. These results indicated the possibility of positive contrast enhancement of lymph nodes on MR imaging using iron colloid.

Animals↗

Inhibition of corneal inflammation by an acylated superoxide dismutase derivative.

Superoxide radicals and their metabolite(s) have been postulated to play an important role in the pathogenesis of inflammation. Hence, superoxide dismutase (SOD) has been used to reduce tissue injury caused by reactive oxygens. However, protection of the cornea and other ocular tissues from oxygen toxicity could not be achieved by administering SOD presumably due to its unfavorable in vivo behavior. To scavenge superoxide radicals on the outer surface of corneal epithelial cells, the authors synthesized an acylated SOD derivative (AC-SOD) by linking capric acid. When instilled into rabbit eyes, a significant amount of AC-SOD remained bound to the corneal surface for a fairly long time. Intracorneal injection of lipopolysaccharide (LPS) triggered infiltration of polymorphonuclear leukocytes (PMNs) to the cornea and induced severe keratitis. Topical administration of AC-SOD to the LPS-treated cornea markedly inhibited the infiltration of PMNs and suppressed the occurrence of keratitis. Under identical conditions, topically administered SOD was rapidly removed by tears and, hence, did not inhibit LPS-induced keratitis. When the number of PMNs in the systemic circulation was reduced by intravenous administration of hydroxyurea, LPS-induced keratitis was inhibited markedly. These results indicate that superoxide radicals and circulating PMNs might play a critical role in LPS-induced keratitis.

Acylation↗

[An early clinical study of Z-100 in leukopenia caused by radiotherapy].

The clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in an early clinical study using three doses, 2, 10 and 20 micrograms. According to the evaluation by investigators and time-course of WBC, the highest effective rate was achieved by 20 micrograms. Adverse reactions occurred in all groups, but there were no serious or clinically relevant reactions. These results suggested that Z-100 is clinically useful for the treatment of leukopenia caused by radiotherapy.

Adult↗

[Silent myocardial ischemia evaluated by ambulatory left ventricular function monitoring].

To determine whether left ventricular function is less disturbed in asymptomatic ischemia than in symptomatic ischemia, exercise-induced left ventricular function was measured in beat-to-beat using an ambulatory left ventricular function monitoring system. The study subjects were 22 patients with coronary artery disease. Supine and sitting ergometer exercise tests were performed. Of 44 exercise tests, 33 showed significant ST depression on electrocardiograms. Among these 33, 17 were asymptomatic: 16, symptomatic. The left ventricular functions during exercise of these 33 were analyzed and compared with those of five normal controls. The changes in end-diastolic volume were not so significant either in controls or in the asymptomatic and symptomatic groups, but the changes in end-systolic volume were reversed in the diseased groups, particularly in the symptomatic group. The changes in ejection fraction (EF), therefore, were significantly negative in the diseased group, particularly in the symptomatic group. The correlation between exercise-induced left ventricular dysfunction and symptoms was evaluated among the 33 patients. Symptoms were present in 35% (6/17) in less than 10% decrease in EF, 44% (4/9) in 10-15% decrease, and 85% (6/7) in greater than or equal to 15% decrease, respectively. Thus, asymptomatic ischemia represents a lesser degree of myocardial ischemia as indicated by mild left ventricular dysfunction, compared with symptomatic ischemia. However, some cases of severe myocardial ischemia did not develop symptoms. We concluded that silent myocardial ischemia is responsible for a lesser degree of myocardial ischemia and decreased pain perception.

Electrocardiography, Ambulatory↗

[Significance of "overshoot" elevation of ejection fraction in early recovery period after exercise in patients with coronary artery disease].

To investigate the relationship between "overshoot" elevation of left ventricular (LV) ejection fraction (EF) in the early recovery period after exercise and myocardial ischemia, LV function was measured in 5 healthy volunteers and 47 pts with coronary artery disease (CAD) using supine ergometer. EF at rest (EFRE), at peak exercise (EFEX), at peak of overshoot (EFOS) and time from cessation of exercise to peak of overshoot (T-OS) were measured using an ambulatory LV function monitor system with a high sensitive CdTe detector. The patients were classified into 3 groups according to EF depression (EFRE-EFEX) by exercise, i.e., D1 (EF decreases less than 5%): 15 pts, D2 (EF decreases 5-10%): 12 pts, D3 (EF decreases greater than or equal to 10%): 20 pts. Degree of overshoot which shows difference in EF between rest and peak of overshoot was 23.8 +/- 2.13% (mean +/- SD) in the normal group, 11.72 +/- 5.12% in D1, 9.56 +/- 6.51 in D2 and 6.12 +/- 4.15% in D3, respectively. T-OS was 1.4 +/- 0.48 in the normal group, 2.8 +/- 0.54 in D1, 4.5 +/- 2.36 in D2 and 5.6 +/- 1.93 min in D3, respectively. We conclude that left ventricular dysfunction was proportionally related to time-lapse from cessation of exercise to peak of overshoot while inversely related to degree of overshoot.

Adult↗

[Transcatheter hepatic arterial chemoembolization using microencapsulated mitomycin C (MMCmc)].

Thirty-six patients with hepatocellular carcinoma were treated by hepatic arterial chemoembolization of microencapslated mitomycin C (MMCmc). The infusion cannulae were placed in the hepatic artery by the Soldinger method, and 10 to 40 mg of MMCmc was injected 1 to 4 times (total doses, 10-110 mg). The evaluation of anti-tumor effects revealed 12 partial responses in 27 evaluable lesions and response rates were 44%. The serum AFP levels were decreased in 70% of patients. The survival rate for 12 months was 35% in all patients, but 67% at Stage III. The control of liver function is also important, because the hepatic failure and esophageal varices were the main causes of death. Side effects such as fever and pain were seen in 70%, but they were mild.

Adult↗

Sequence of mechanical and electrical changes during myocardial ischemia: assessment by an ambulatory left ventricular function monitor.

To investigate the relationship between left ventricular function and electrical changes during myocardial ischemia, ambulatory left ventricular function monitoring and ECG recording were made during the ergometer exercise test in 14 patients with coronary artery disease. An ambulatory ventricular function monitor consists of a small cadmium telluride (CdTe) radionuclide probe (250 g) affixed to the patient's chest wall, a preamplifer (10 g), and a portable data acquisition unit (600 g). Left ventricular time-activity curves were recorded continuously using this monitor, and the end-systolic count (volume), end-diastolic count (volume) and ejection fraction were calculated after background subtraction. Twenty-eight exercise tests were performed in the supine and upright positions. In 15 tests, left ventricular dysfunction, i.e., an increase in the end-systolic count (greater than or equal to 10%) and a decrease in ejection fraction (greater than or equal to 5%), and ST depression (greater than or equal to 0.1 mV) were observed. In these 15 tests, exercise duration was 362 +/- 27 sec. Left ventricular dysfunction occurred earlier than ST depression and the time difference was 97 +/- 19 sec. Left ventricular function recovered 33 +/- 8.5 sec after discontinuation of exercise, while ST depression continued for the additional 85 +/- 18.5 sec after recovery of left ventricular function. In conclusion, 1) left ventricular dysfunction occurs earlier than electrical changes during exercise-induced ischemia; 2) left ventricular dysfunction improves earlier than electrical changes after exercise; and 3) the same temporal sequence exists in the restoration from myocardial ischemia.

Coronary Disease↗

[Uneven fractionation irradiation].

To get the better therapeutic ratio with low LET radiation therapy alone, the improvement of the physical dose distribution and the mode of dose fractionation are required. Since 1972, uneven fractionation irradiation with electron beam has been used for head and neck tumors. The 2 year control rates for primary tongue cancer T1, T2 and T3 by this method were approximately comparable to that of the small source implantation. In the treatment results for the cervical lymph node metastasis, uneven fractionation technique is superior to conventional one. Furthermore, this results was reviewed by means of multivariate analysis.

Analysis of Variance↗

Enhancement of vascular permeability upon serratial infection: activation of Hageman factor--kallikrein--kinin cascade.

A zinc dependent serratial 56K protease caused enhancement of vascular permeability followed by edema formation when injected into the guinea pig peripheral cornea, the subconjunctival space, or the skin. Because this enhancement was not affected by antihistamine, involvement of the kinin-generating system in this permeability enhancement was investigated. The 56K protease induced permeability much greater extent than that by bradykinin on weight basis, and more so on molar basis. The phenomenon was inhibited by soybean trypsin inhibitor, a well known inhibitor of plasma kallikrein, and also by corn trypsin inhibitor, which is the best inhibitor of the activated Hageman factor. In vitro experiments using numbers of synthetic peptide substrates, the 56K protease exhibited a similar substrate specificity to that of plasma kallikrein. Kallikrein is a known endogenous activator of Hageman factor. The enhancement by 56K protease was greatly augmented by inhibition of kininase II with Glu-Trp-Arg-Pro-Gln-Ile-Pro-Pro-OH (SQ 20,881), suggesting generation of bradykinin. Thus, these results indicate that the enhancement of vascular permeability induced by the 56K protease is caused by an activation of Hageman factor by 56K protease followed by subsequent activation of cascade amplification, and resulted in kinin generation in vivo.

Animals↗