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Biomedical subjects

T Otani

Publications and source records attributed to T Otani.

At least 235 records · Page 13Linked to original sources
PubMed1988

Stimulation of non-specific resistance to infection by muroctasin.

The profile of the stimulant activity of a muramyl dipeptide (MDP) analog, N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) on the host resistance to infection was clarified through the following results. A comparative study of parent MDP and MDP-Lys(L18) in relation to the protection against infection with various pathogens revealed the same spectrum of antiinfectious activity, but a different potency: the greater strength of MDP-Lys(L18) was demonstrated both by the smaller influence of bacterial inoculum size on its activity and by the smaller minimal dosage required for inducing significant activity. The superiority of the oral application of MDP-Lys(L18) over MDP was also demonstrated. The protective activity of the compound was substantially influenced by the timing of treatment, the greatest activity being achieved by treatment 1 day before infection. Furthermore, treatment with MDP-Lys(L18) restored the depressed resistance induced by cyclophosphamide to systemic infection with E. coli in mice, and that induced by cortisone acetate to bacteremic pneumonia with P. aeruginosa in guinea pigs. The chemotherapeutic efficacy of antibiotics on E. coli infection was potentiated by combined use of MDP-Lys(L18) for normal mice and mice immunosuppressed with cyclophosphamide. From these findings, enhancement of the host resistance to infection by MDP-Lys(L18) may be an important aspect in the future evaluation of therapy for infection in immunocompromised patients. Finally, since the compound augmented 1. the function of polymorphonuclear leukocytes, such as chemotaxis, phagocytosis, and superoxide anion generating capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Phase I study and clinical pharmacological study of muroctasin.

In a first part a phase I clinical study on the immunomodulator N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) in male healthy volunteers was performed to assess safety, immunological activities, and preliminary pharmacokinetics of the drug by subcutaneous administration. 1. Safety Slight increase (38 degrees C) in body temperature was observed in a high-dose group by subcutaneous administration. Redness was noted as a change in the injection site, but no dose-dependency was seen in this respect. No other noticeable subjective nor objective symptoms were detected. On the other hand, positive C-reactive protein (CRP) (1 case out of 35) and slight increase in gamma-glutamyl transpeptidase (gamma-GTP, 1 case out of 35) associated with the use of this drug were observed. But the causal relationship of gamma-GTP with this drug was not clear because the finding returned to normal value during the treatment. 2. Immunological activities and leucocyte count Mitogenic responses of lymphocytes were augmented after subcutaneous administration of this drug. Increase in peripheral leukocyte count was also observed. This was due to the increase in neutrophil count. 3. Pharmacokinetics Pharmacokinetic parameters (maximum serum levels, area under serum concentration-time curve, time to reach maximum blood level, biological half-life) were obtained after a single administration of 400 micrograms: Cmax: 6.93 +/- 1.32 ng/ml (mean +/- SE), AUC: 37.22 +/- 6.51 ng/ml/h, tmax: 1.32 +/- 0.26 h and t1/2: 2.7 +/- 0.8 h. The safety of subcutaneous administration of MDP-Lys (L18) injection has been confirmed in 35 male healthy volunteers. It was suggested that adequate doses for phase II studies in patients were 200 micrograms to 400 micrograms. In a second part a clinical pharmacological study (single subcutaneous administrations of 100 micrograms and 200 micrograms and multiple 5 day subcutaneous administration of 200 micrograms of MDP-Lys (L18) was performed on male healthy volunteers to assess pharmacokinetics, effect on leukocyte function and on immune system, and safety: 1. Pharmacokinetics a) serum concentration after single administration Cmax in 100 micrograms and 200 micrograms were 1.48 and 2.78 ng/ml, respectively. The AUC values were 6.71 and 15.62 ng/ml/h, respectively, with dose dependency.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Beneficial effect of muroctasin on experimental leukopenia induced by cyclophosphamide or irradiation in mice.

Subcutaneous injection of N2-[N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, favoured recovery of mice from experimental leukopenia induced by cyclophosphamide or by irradiation with X-rays. These effects were observed only when MDP-Lys(L18) treatment occurred after cyclophosphamide injection or X-ray irradiation. Prophylactic treatment resulted in neither preventive nor restorative efficacy on leukopenia. In contrast, glutathione was hardly effective on leukopenia in both models, irrespective of treatment timing. The restorative efficacy of muroctasin was found to be dose-dependent and to be attributable at least to its augmenting effect on colony-stimulating factor production, followed by the marked proliferation and differentiation of myeloblasts towards mature granulocytes in the bone marrow. These beneficial effects of MDP-Lys(L18) warrant further evaluation of its clinical usefulness.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

[Indications for and limitations of HpD photodynamic therapy for esophageal cancer and gastric cancer].

HpD photodynamic therapy (PDT) was performed on 4 patients with superficial esophageal cancer, 20 patients with 22 early gastric cancer lesions and one patient with advanced gastric cancer. About 50 h before irradiation, 3 mg/kg of HpD or 1.3-2.5 mg/kg of Photofrin II was injected intravenously. The entire lesion including a 5-mm border of normal surrounding mucosa, was irradiated with an argon dye laser at 630nm wavelength with an output of 100-400mW at the tip of the fiber. Complete response (CR) to HpD-PDT was obtained in 2 of 2 mucosal esophageal cancers, and one of 2 submucosal lesions, totalling 3 of 4, and in 13 of 13 mucosal gastric cancers and 7 of 9 submucosal lesions totalling 20 of 22. The depths of cancer involvement were determined endoscopically. In Borrmann 1 lesion with muscularis externa involvement, in spite of two trials with HpD-PDT, only partial response (PR) was obtained. Tumor laser dose had to be more than 90 J/cm2, and in several cases combined hot biopsy with electrodiathermy and/or repeated HpD-PDT was needed to obtain CR. HpD-PDT is indicated for superficial esophageal cancer and depressed and/or assembled protuberant-type of early gastric cancer with poor risk.

Aged↗
PubMed1988

[Clinical effects of oxybutynin hydrochloride in the treatment of unstable bladder and overactive neurogenic bladder: a long-term clinical trial].

Clinical effects and therapeutic usefulness of oxybutynin hydrochloride were evaluated in a long-term clinical trial on patients with unstable bladders and neurogenic bladders. Of the 46 patients entered into the trial, 37 were those diagnosed with an unstable bladder and 9 with a neurogenic bladder with overactive detrusor. In 37 of the cases (80%), the period of drug administration reached up to 12 weeks and in 16 cases (34%) the drugs were administered for more than 24 weeks. The average administration period was 165.9 days. The average total given dose was 1776.9 mg and average dose per day was 10.7 mg. Excellent and good responses were obtained in 76.3, 88.9 and 69.6% at 12 and 24 weeks after start of administration and at the time of discontinuing the drug, respectively. The cystometric changes at pre- and post-administration were evaluated on 23 cases and revealed a significant increase in volume at first sensation and maximum desire to void. Maximum resting intravesical pressure was significantly declined and uninhibited detrusor contractions were significantly suppressed. Side effects were noted in 11 of the 46 cases (23.9%), most of which were well tolerated by the patients. In 4 cases the drug had to be discontinued because of the side effects. Dry mouth was the most common side effect, occupying almost half of the incidents. No significant abnormality was noted on blood laboratory data, blood pressure or heart rate, following the drug administration. In one case slight increase in serum glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase was encountered, but its relationship with the drug was obscure. The clinical usefulness of this drug (excellent and good) was 78.9, 88.9 and 69.6% at 12 and 24 weeks after start of administration, and at the time of drug discontinuation, respectively. The present long-term trial proved that oxybutynin hydrochloride is an exceedingly effective and safe agent for clinical management of unstable bladder and overactive neurogenic bladder.

Adolescent↗
PubMed1987

Gonadotropin alpha subunit. Differential processing of free and combined forms in human trophoblast and transfected mouse cells.

The gonadotropins luteinizing hormone, follicle-stimulating hormone, and human chorionic gonadotropin are composed of two noncovalently linked subunits, alpha and beta. The alpha subunit, identical in all three hormones, is produced in excess over the unique beta subunits by pituitary and placenta, and is secreted as uncombined, or free subunit. Free alpha subunit from both tissues has a larger molecular weight than the dimer form. In bovine pituitary an extra O-linked oligosaccharide is added to free alpha subunit, and this modification has recently been detected at an analogous position (threonine 39) on human alpha subunit secreted by choriocarcinoma cells. To assess the contribution of N-linked and O-linked oligosaccharides to the heterogeneity of human free alpha subunit, we have compared free alpha with human chorionic gonadotropin alpha secreted by explants and cultured cytotrophoblasts of human first trimester placenta. We have also examined the free and combined forms of human alpha subunit expressed in transfected C-127 mouse mammary tumor cells. Processing of the alpha subunit in placental and C-127 cells was similar. Tryptic mapping of placental-derived and transfected alpha subunits indicated that O-glycosylation at threonine 39 was not a major modification. In the presence of the oligosaccharide processing inhibitor swainsonine the difference in size between the free and combined forms of alpha was eliminated in both placental and C-127 cells, indicating that the two forms of alpha differed in their N-linked oligosaccharides. Furthermore, the oligosaccharides of free alpha subunits from placental and transfected cells were resistant to endoglycosidase H, but the combined forms of alpha were partially sensitive to the enzyme. Thus, in human first trimester placenta and mouse C-127 cells, combination of alpha with human chorionic gonadotropin beta alters the processing of N-linked oligosaccharides on alpha subunit.

Alkaloids↗
PubMed1987

Cosmid mapping of the human chorionic gonadotropin beta subunit genes by field-inversion gel electrophoresis.

A cosmid clone containing the entire hCG beta gene cluster has been isolated. The restriction map of this clone has been determined by an indirect-end-label FIGE (field inversion gel electrophoresis) method. Analysis of this cosmid clone shows that there are 6 hCG beta genes in human genomic DNA. A previously uncloned portion of the hCG beta cluster, termed the "gap" region, has been shown not to contain any sequences homologous to the hCG beta cDNA. The restriction mapping method employed in this study takes advantage of the superior resolution of FIGE for high molecular weight DNA fragments in the size range 15-50 kb. This method is broadly applicable and permits rapid and accurate restriction mapping for extended regions of genomic DNA that have been cloned into cosmid or lambda vectors.

Chorionic Gonadotropin↗
PubMed1987

The effects of ultraviolet irradiation of the skin on herpes simplex virus infection: alteration in immune function mediated by epidermal cells and in the course of infection.

Previously, we demonstrated that Ia+ epidermal cells (EC) have herpes simplex virus (HSV) antigen-presenting capacity in vitro and play an important role in resistance to HSV infection in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the HSV-immunity function of EC both in vitro and in vivo and on the pathogenesis of HSV infection. Immune T cells cultured with EC and HSV antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected nude mice. Immune T cells stimulated with EC obtained from irradiated mice did not effectively clear HSV and allowed development of zosteriform skin lesions. In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform rash. In addition, mice irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of HSV showed increased severity of infection and a higher incidence of latency compared with control mice. These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects HSV pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent HSV infections is discussed.

Animals↗
PubMed1987

Palliative laser therapy.

Endoscopic laser treatment has been tried for hemostasis, relief of stenosis and reduction of tumor volume in advanced upper gastrointestinal cancer. This form of treatment was found to be effective for each purpose, but success was usually only temporary. Thus, it was considered that endoscopic laser therapy for problems of advanced upper GI cancer could perhaps be improved by modifying the technique and/or developing new methods, such as the combination of the laser with other therapies.

Aged↗
PubMed1987

Correction of reflux with the ureteric crossover method. Clinical experience in 50 patients.

We describe 50 consecutive patients who underwent anti-reflux surgery with the ureteric crossover method; 32 had primary and 18 had secondary reflux. The surgical procedure was characterised by the fact that the ureters crossed and overlapped each other at their middle portion submucosally. The surgical success rate was 100% for primary reflux patients and 89% for those with secondary reflux. It was concluded that the ureteric crossover method was a safe and effective anti-reflux procedure.

Adolescent↗
PubMed1987

[Clinical study of bunazosin hydrochloride, an alpha 1-adrenergic blocker, in benign prostatic obstruction and neurogenic bladder dysfunction].

A newly developed alpha 1-adrenergic blocker, bunazosin hydrochloride (Detantol, Eisai) was clinically investigated in 17 patients with benign prostatic obstruction and 18 patients with neurogenic bladder dysfunction. Subjective symptoms improved in 11 of the 17 cases (64.7%) with prostatic obstruction and in 4 of the 10 cases (40%) with neurogenic bladder dysfunction. Dose-dependent subjective improvement was observed with dosages of 3 to 9 mg/day. A dosage of 12 mg/day did not improve subjective symptoms more than did the 9 mg/day dose. In prostatic obstruction, 7 of the 10 objective parameters improved significantly. However, for neurogenic bladder dysfunction, only two parameters improved significantly. Improvements in objective findings were generally dose-dependent in cases of prostatic obstruction, but not in neurogenic bladder dysfunction. Mild side effects, none of them serious, were reported in 9 of the total 35 cases (26%). They generally consisted of dizziness, nasal obstruction and headache. Comprehensive improvement, i.e., improvement of both subjective symptoms and objective parameters, occurred in 11 of the 17 cases (64.7%) of prostatic obstruction and 6 of the 18 cases (33.3%) of neurogenic bladder dysfunction.

Adolescent↗
PubMed1987

Lack of effectiveness of ofloxacin against experimental syphilis in rabbits.

Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in experimental syphilis in rabbits in comparison with penicillin G. Experimental syphilis was established by intradermal injection of Treponema pallidum subsp. pallidum Nichols. Ten days after infection, the dermal lesions were characterized by syphilitic papula accompanied with central necrosis. These animals were subsequently treated either with ofloxacin twice a day at an oral dose of 10 mg/kg or with penicillin G once a day at an intramuscular dose of 10,000 U/kg for 21 consecutive days. In penicillin G-treated animals, the dermal lesions became smaller as early as day 3 of treatment and almost disappeared during the therapy. In marked contrast to remarkable efficacy of penicillin G was further development of the lesions in ofloxacin-treated animals, showing no difference in pathological manifestations as compared to untreated animals. The results of nontreponemal serologic test correlated well with the response of animals to treatment.

Animals↗
PubMed1987

[Serum beta 2-microglobulin in spinal cord injury patients--its efficacy as a screening test of renal function].

We evaluated the reliability of serum beta 2-microglobulin (beta 2-MG) in comparison with serum creatinine, blood urea nitrogen and creatinine clearance in 164 patients with spinal cord injury. The value of serum beta 2-MG demonstrated the highest correlation coefficient (r = -0.927) in relation to creatinine clearance. The beta 2-MG value reflected the severity of hydronephrosis on excretory urography, with very few false negative values. The value of beta 2-MG is concluded to be one of the best screening tests in evaluating renal function in spinal cord injury patients.

Female↗
PubMed1987

[Perivesical abscess associated with neurogenic bladders: report of two cases].

We report two cases of perivesical abscess associated with neurogenic bladders. One patient suffered from diabetic neurogenic bladder, and the other spinal cord injury. Both patients had an uninhibited contraction at the low capacity on cystometry. They complained of difficulty in micturition and presented with large lower abdominal tumors. Although the extravasation of contrast medium was not confirmed on cystography, we believe that the perivesical abscess was the consequence of urinary leakage out of the bladder. The abscesses disappeared after drainage. We have discussed the possible mechanism involved in the abscess formation which occurred in the neurogenic bladders.

Abscess↗
PubMed1986

A paraplegic fathering a child after an intrathecal injection of neostigmine: case report.

This paper reports a 33-year-old male paraplegic (T6) who fathered a child by artificial insemination following an intrathecal injection of neostigmine. His wife was healthy and pregnancy was achieved after the 10th insemination. She delivered a mature female child weighing 3,100 g in August 1984. To our knowledge this is only the fourth successful case in the world following neostigmine injection.

Adult↗
PubMed1986

In vitro activity of DQ-2556, a new cephalosporin.

The in vitro antibacterial activity of DQ-2556, a new semisynthetic cephalosporin, was compared with that of ceftazidime and cefotaxime. The activity of DQ-2556 against members of the family Enterobacteriaceae was roughly comparable to that of cefotaxime. Against Pseudomonas aeruginosa, DQ-2556 was slightly less active than ceftazidime. DQ-2556 was more active than the reference cephalosporins against staphylococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DQ-2556.

Bacteria↗