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Biomedical subjects

M Ohkoshi

Publications and source records attributed to M Ohkoshi.

At least 19 recordsLinked to original sources

Uveitopathogenic sites in recoverin.

PURPOSE: This study was carried out in order to determine the most potent and novel uveitopathogenic sites of recoverin using synthetic peptides. METHODS: Several synthetic peptides containing the recoverin sequence plus adjuvants were injected into Lewis rats, and the uveitopathogenic sequence was defined, clinically, histologically, and immunologically. RESULTS: Peptides containing of amino acids 57-85 and 136-167 induced severe EAU, and the lowest doses to induce EAU were 20 microg and 10 microg, respectively. Lymphocyte proliferative reactions were also positive for peptides 57-85 and 136-167. The core sequences within the uveitopathogenic site were 65-79 and 153-164. Peptides of amino acids 65-79 within 57-85 and 149-167 within 136-167 were the smallest in the recoverin sequence, respectively, that could induce severe EAU. CONCLUSION: We found recoverin has some novel potent uveitopathogenic sites, 149-167. These findings of the uveitopathogenic sites in recoverin may lead to improved understanding of the pathogenesis of uveitis and the means to design specific treatment.

Animals↗

Identification of the hexon region of an adenovirus involved in a new outbreak of keratoconjunctivitis.

We tested 15 adenovirus (Ad)-positive patients involved in a case of nosocomial spread of keratoconjunctivitis. A neutralization test, PCR-restriction fragment length polymorphism analysis, and sequencing of the hypervariable regions of the hexons were performed in order to identify the type of Ad involved. The serotype of the Ad was not identical to any published Ad sequence by either method.

Adenovirus Infections, Human↗

Potent growth-suppressive activity of a serine protease inhibitor, ONO-3403, toward malignant human neuroblastoma cell lines.

FOY-305 is a synthetic serine protease inhibitor and ONO-3403 and FO-349 are its derivatives. The effects of these compounds on the proliferation of 13 human neuroblastoma cell lines were investigated in vitro by MTT colorimetric assay. The half maximum inhibition concentrations of ONO-3403 varied between 22 and 90 microg/ml while those of FOY-305 and FO-349 were higher than 100 microg/ml. ONO-3403 showed higher growth-inhibitory activity for N-myc-amplified neuroblastomas as compared with that for non-amplified cells. Since N-myc amplification in neuroblastomas is well correlated with a poor prognosis, ONO-3403 could be an effective anticancer drug for malignant neuroblastomas.

Allylglycine↗

Analysis of uveitogenic sites in phosducin molecule.

PURPOSE: Phosducin, a retinal photoreceptor protein, induces experimental autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptides. METHODS: Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC. First, 13 peptides covering the entire sequence of phosducin were synthesized, and each was injected into the hind footpad of Lewis rats for immunization, and induction of EAU was examined clinically and histologically. Next, peptides that appeared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. RESULTS: Of the 13 peptides used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior chamber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and serous retinal detachment was found in cases of severe inflammation. Infiltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino acid sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunized with these peptides also exhibited high value on lymphocyte proliferation assay. CONCLUSION: Phosducin has 5 uveitogenic sites. Among others, one of them has potent and others weak uveitogenicity.

Amino Acid Sequence↗

[Protease inhibitors as anticancer chemotherapy--experimental and clinical studies].

A synthetic protease inhibitor FOY-305 (Foypan) not only inhibited the skin tumorigenesis in mice but also suppressed the growth of autochthonous solid tumor in mice. Furthermore, administration of FOY-305 inhibited the metastasis of Lewis lung carcinoma and colon adenocarcinoma to the lung in mice, experimentally and spontaneously. Clinically, FOY-305 prevented both recurrence and metastasis in the patients who had received many anticancer drugs. In 2 terminal secondary cases, tumor remission and elongation of survival time were observed. Above results suggest a possibility for applying a new type chemotherapy using protease inhibitors.

Adenocarcinoma↗

[Proposal of a standard method for clinical evaluation of antimicrobial agents in prostatitis--specifications of patients and criteria for evaluation of clinical efficacy].

The criteria for clinical evaluation of the efficacy of antimicrobial agents on prostatitis were proposed. Nomenclatural definition, specifications of patients and criteria were as follows. Acute prostatitis: Target infection is acute bacterial prostatitis with no underlying condition in urinary tract. The findings of swelling and tenderness of prostate by rectal examination are essential. The patients are between 16 and 69 years old. They have fever greater than 37 degrees C and pain on micturition. Microscopic examination reveals white blood cells (WBCs) in VB1 or VB2 before treatment greater than or equal to 10 cells/hpf. Viable bacteria in VB1 or VB2 before treatment are greater than or equal to 10(4) bacteria/ml. Period of treatment is for 7 days. To evaluate clinical efficacy, 3 days after administration, changes of symptoms (fever and pain on micturition) are recorded. Seven days after administration, changes of symptoms, microscopic examinations and number of bacteria are recorded. The overall clinical efficacy is graded as "excellent", "moderate" or "poor" by combining changes in the above 3 parameters. Chronic prostatitis: Target infection is chronic bacterial prostatitis with no underlying condition in urinary tract. The patients are between 16 and 69 years old. Microscopic examination reveals WBC in EPS or VB3 before treatment greater than or equal to 10 cells/hpf. Viable bacteria before treatment are greater than or equal to 10(3)/ml (GNR) or greater than or equal to 10(4)/ml (GPC). Treatment period is for 14 days. To evaluate clinical efficacy, after 14 days of administration, changes of symptoms, microscopic examinations and number of bacteria are recorded. The overall clinical efficacy is graded as "excellent", "moderate", or "poor" by combining the changes in the 2 parameters, microscopic examination and number of bacteria.

Adolescent↗

[Well-controlled comparative study on aztreonam and cefoperazone in the treatment of complicated urinary tract infections].

A well-controlled comparative study was conducted in order to evaluate the efficacy, safety and usefulness of the monobactam antibiotic aztreonam (AZT) in complicated urinary tract infections (UTI) using cefoperazone (CPZ) as the control drug. Patients with complicated UTI due to Gram-negative bacteria were examined. However, in polymicrobial infections, the cases caused by Gram-negative and Gram-positive bacteria were also examined. Both drugs were administered 1 g, twice a day by intravenous drip infusion for 5 days. Overall clinical efficacy was evaluated by the criteria proposed by the UTI committee in Japan. Of the total 394 cases, the clinical efficacy was evaluated for 152 cases in the AZT group and 143 cases in the CPZ group excluding 99 cases of exclusion or dropout. There was no statistically significant difference in the back ground characteristics between the 2 groups. The overall clinical efficacy rate was 55.3% for AZT and 55.2% for CPZ with difference not significant. As for clinical efficacy, in the monomicrobial infection after postprostatectomy (G-2), AZT was superior to CPZ (P less than 0.05), whereas in the polymicrobial infection without indwelling catheter (G-6), CPZ was superior to AZT (P less than 0.1). The overall bacteriological eradication rate was 77.2% for AZT and 74.5% for CPZ. For Gram-negative bacteria only the eradication rate for AZT (83.2%) was superior to that for CPZ (74.6%). This was probably due to the stability of AZT to beta-lactamase. Side effects were observed in 3 cases out of 201 in the AZT group and 5 cases out of 189 in the CPZ group. No severe abnormal laboratory finding was observed in any group; there was no significant difference between the 2 groups. Consequently, AZT was judged to be an antibiotic with clinical usefulness equal to, or even superior to that of CPZ.

Adolescent↗

[Recurrence of acute uncomplicated cystitis--criteria for the evaluation of recurrence after antimicrobial chemotherapy].

UNLABELLED: The recurrence of female acute uncomplicated cystitis was investigated clinically. The criteria for the evaluation of recurrences were proposed, as follows; PATIENTS: Target infection is acute uncomplicated cystitis (AUC) which had satisfied the specifications of AUC Criteria by the UTI Committee of Japan and showed the excellent effects of an antimicrobial agent after a definite period of administration. Treatment period: Seven days; after 3 days' administration to evaluate the drug efficacy, patients shall take an additional 4 days' treatment. Interval of follow up proposed was 7 days. Evaluation of recurrence: Parameters of criteria are pyuria and bacteriuria. Recurrence: Pyuria greater than or equal to 10 WBCs/hpf and bacteriuria greater than or equal to 10(4)/ml. Evaluation of the day of recurrence: Evaluation should be made 14 days after the start of treatment. Urine sampling: After 7 days of treatment, midstream urine is collected and in cases with positive findings, catheterized urine should then be collected. Using these criteria it will be possible to evaluate and compare the ability of various antimicrobial agents to cure acute uncomplicated cystitis.

Acute Disease↗

[Tuberculosis of the penis: report of a case and review of the literature].

Tuberculosis of the penis is a rare disease. We report a case of tuberculosis of the penis. A 51-year-old man noticed a painless induration with a central ulceration on the glans penis. He had a history of tuberculosis of cervical lymph-nodes, right epididymis and leg skin. Examination of the other parts showed no evidence of tuberculosis. Tuberculin test was strongly positive. The skin lesion of the glans was excised. The pathology was epithelioid cell granuloma with Langhans' giant cell, indicative of tuberculosis. But acid-fast bacilli were not detected in the Ziehl-Neelsen preparation of the tissue. The patient was treated with isoniazid, rifampicin and cycloserine. After the treatment for approximately 5 months, recurrence was not observed and enlargement of cervical lymphadenopathy improved. We reviewed 39 cases of tuberculosis of the penis reported in Japan during the past 14 years.

Antitubercular Agents↗

[The problem in the incubation of injective solutions. The difference between ampule and vial].

Variations in the actual doses with vials and ampules due to causes of dosage forms and human operations have been discussed. The differences between the labeled doses and actually administered doses with ampules and vials have been studied. The comparison of resulting blood levels revealed peaks of 4.88 +/- 1.08 micrograms/ml and 3.85 +/- 0.71 micrograms/ml actually determined with ampule preparations and vial preparations, respectively, showing some appreciable differences. These values were analyzed with compartment models. Cmax values were 5.13 micrograms/ml and 3.94 micrograms/ml, respectively, showing significant differences (P less than 0.05) between the ampule and vial preparations. However, AUC and Tmax values were equal to each other, so that it was assumed that there would be no problem about the similarity of the 2 types of dosage forms. As to the differences due to human operations, the nurse A did normally collect only 83.0% (75.2 mg) volume of the labeled doses of vials, and, even when she did it with greater care, she collected still 90.0% (81.5 mg) of the labeled doses. On the other hand, the nurse B normally collected 89.8% (81.4 mg) of the labeled dose of vials, and when she used greater care, she collected 92.4% (83.7 mg) of the labeled doses. In the group of ampule preparations, the nurses A and B collected 93.1% (94.8 mg) and 98.1% (99.9 mg), respectively. It was beyond the amount expected in advance for the actually collected dose from ampules. The differences in the collected doses between ampules and vials were within the expected range because ampule preparations usually contain approximate 10% overage, but as to the differences added to this difference due to the human operations, the nearly twice as much speed for collecting the filled preparation by the nurse A would not have been denied for the smaller doses collected on the basis of the above-mentioned results. It was noted therefore that care should be taken in collecting the filled doses from containers into injection syringes.

Adult↗

Clinical experience with a protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate for prevention of recurrence of carcinoma of the mouth and in treatment of terminal carcinoma.

A protease inhibitor, (N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate) methanesulfate was administered orally 3 times daily to 9 patients with squamous cell carcinoma of the oral cavity, at doses ranging from 0.6 g. to 7.2 g. Seven of 9 patients who had undergone all kinds of therapies were observed to see whether recurrence was prevented and in no case did the tumour recur. Also, in 2 terminal secondary cases tumour remission resulted. Histologically, after this therapy, carcinomatous lesions showed marked hyperkeratosis in 2 cases and the survival time in 1 case was markedly prolonged. Haematological and gastrointestinal toxicity was almost never observed at these doses.

Adult↗

[Antipseudomonal activities of new cephem antibiotics].

The antipseudomonal activity of so-called third and subsequent generation cephems was evaluated. The third and subsequent generation cephems have been reported to have antibacterial activity against Pseudomonas aeruginosa. Their potency and clinical efficacy against pseudomonal infections, however, vary from drug to drug. Judging from our experience and our review of the literature, the four drugs, cefsulodin, cefoperazone, cefpiramide and ceftazidime are of value in clinical practice, though the effect of these drugs is not sufficient. In view of the fact that concomitant use of cefsulodin and cefmenoxime eradicated Pseudomonas aeruginosa in as much as 82.9% of the patients who had complicated UTI due to Pseudomonas aeruginosa, concomitant therapy of these four drugs in various combinations is a future subject to be studied.

Cephalosporins↗

[Studies on tobramycin by the intravenous drip infusion method].

Fundamental and clinical efficacy evaluation has been made in the study on the therapy with intravenous drip infusion of tobramycin (TOB) which is one of the aminoglycoside antibiotics and which has been recently approved of intravenous administration. The fundamental evaluations were made with intravenous drip infusion of 60 mg of TOB for 1 hour and that of 120 mg of TOB for 2 hours to 4 healthy adult volunteers on crossover method. Follow-up determinations were made for comparison on its concentrations in blood and urine samples which were collected both at intervals thereafter, using 2 assay methods of the bioassay and the EMIT methods. The maximum blood level of TOB based on the intravenous drip infusion of 60 mg for 1 hour was 5.9 micrograms/ml and 4.6 micrograms/ml by the bioassay and the EMIT methods at the end of intravenous drip infusion, respectively, and 0.3 micrograms/ml and 0.4 micrograms/ml, respectively, at 6 hours after the drip infusion. The T 1/2 value was 1.81 hours with bioassay and 2.41 hours with the EMIT method. The maximum blood level of TOB through drip infusion method of 120 mg of TOB for 2 hours was 7.5 micrograms/ml by bioassay and 5.8 micrograms/ml by EMIT method. The T 1/2 value was 1.87 hours and 1.99 hours, respectively. The recovery rate of TOB from urine until 24 hours after the administration was 83.0% and 94.4% with the doses of 60 mg and 120 mg, respectively, which were determined only with the bioassay. The correlation coefficient between the agar well method and the EMIT method was 0.963 and 0.972 in the groups of intravenous drip infusion of 60 mg for 1 hour and 120 mg for 2 hours, respectively, showing proximity to each other. TOB was kept administered with a daily dose of 120 mg at a time to 11 cases and at 2 times to 1 case with chronic complicated infections of urinary tracts (comprising 9 cases with chronic complicated cystitis, 2 with chronic complicated pyelonephritis, and 1 with acute epididymitis). Of the 12 patients, 8 could meet the criteria for evaluation of drug efficacy and 6 of them proved to be effective, while 2 were ineffective. The efficacy rate was so high as 75%. The rate of disappearance of bacteria was 80.0%, which was very high. No side effect was specifically found out, except 1 case showing slight rise in S-GOT.

Adult↗