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Biomedical subjects

A Higuchi

Publications and source records attributed to A Higuchi.

At least 19 recordsLinked to original sources
PubMed1992

13C-NMR spectral analysis of the structures of mouse immunoglobulin G1 carrying allotypes a and j.

A novel 13C nuclear magnetic resonance (NMR) method is described for the detection of subtle structural differences between mouse immunoglobulins carrying different allotypes. Fc fragments of mouse IgG1 antibodies carrying allotypes a and j have been selectively labeled with [1-13C]methionine. 13C-NMR spectra have shown that the microenvironment around Met-398 is significantly different for the two kinds of allotypes. Peptide mapping and amino acid sequence analyses have revealed that Val-406 of IgG1 carrying allotype a is substituted for Ile in the case of allotype j. X-ray crystallographic data indicate that Met-398 is in close spatial proximity to Val (Ile)-406. We therefore conclude that the 13C-NMR method can provide us with a novel spectroscopic probe for the structural characterization of allotypic markers.

Amino Acid Sequence↗
PubMed1992

Temperature-sensitive immunoglobulin A-binding and dimerization of C-terminus-impaired protein Arp4 produced in Escherichia coli.

A gene for protein Arp4, an IgA receptor protein derived from Streptococcus pyogenes AP4, was expressed in Escherichia coli. The product was demonstrated to be accumulated in a periplasmic space as a polypeptide with an apparent molecular weight of 40 kDa with the deleted C-terminal membrane anchor portion of protein Arp4. This 40-kDa peptide of the C-terminus-impaired recombinant protein Arp4 produced in E. coli, designated ir-protein Arp4, was purified from a periplasmic fraction of transformants and its IgA-binding activity was analyzed. The IgA binding of ir-protein Arp4 was temperature-sensitive, that is, ir-protein Arp4 bound IgA at 4 and 25 C, but did not at 37 C. In addition, the dimerization of ir-protein Arp4 was also temperature-sensitive in parallel with temperature-dependent binding activity, suggesting that the dimerization of ir-protein Arp4 may be required for its active binding to IgA. In contrast, ir-protein Arp4 immobilized on Sepharose 4B did bind to IgA even at 37 C as well as 4 and 25 C. The immobilized ir-protein Arp4 might acquire the temperature-resistant IgA binding activity in part through the formation of a stable dimerized ir-protein Arp4 on the solid support.

Bacterial Proteins↗
PubMed1992

Binding of monoclonal antibody specific for domain Ia/II of Pseudomonas aeruginosa exotoxin A at pH 4 strongly neutralizes exotoxin A-induced cytotoxicity in cell culture and in vivo.

Mouse monoclonal antibodies (MAbs) against Pseudomonas aeruginosa exotoxin A (Ex-A) were established, and 4 of 20 MAbs were extensively studied for analysis of the structure-function relationship of Ex-A. IN vivo experiments demonstrated that MAb Ex-3C7 protected mice either injected with Ex-A or infected with Ex-A-producing P. aeruginosa from death caused by Ex-A at the highest rate, followed by MAbs Ex-4F2 and Ex-8H5, in that order. MAb Ex-2A10 failed to rescue the mice. MAb Ex-3C7 (immunoglobulin G1 [IgG1]) inhibited incorporation of Ex-A into target cells and strongly neutralized cytotoxicity in cell culture but did not inhibit an enzymatic activity of Ex-A, ADP-ribosyltransferase, at all. The MAb also bound Ex-A, even at a low pH of 4, and recognized amino acid residues 241 to 297 (domain Ia/II), suggesting that MAb Ex-3C7 can interfere with the conformational change and/or processing of Ex-A by keeping a complex of Ex-A and antibody stable at low pH in the phagolysosome. MAb Ex-4F2 (IgG1), which recognizes residues 550 to 590 (domain III), strongly inhibited Ex-A incorporation and neutralized cytotoxicity in cell culture but only weakly inhibited ADP-ribosyltransferase. MAb Ex-8H5 (IgG1), which recognizes residues 591 to 613 (domain III), also inhibited cytotoxicity in cell culture, but weakly. In contrast to the above three MAbs, MAb Ex-2A10 (IgG2b) greatly inhibited ADP-ribosyltransferase but showed no inhibition of Ex-A incorporation and no neutralizing activity against cell toxicity. A line of evidence indicates that (i) domain Ia/II plays an important role in the pathogenesis of Ex-A and (ii) MAbs that inhibit an intracellular postbinding process, such as conformational change, processing, and translocation of Ex-A in target cells, can display potent inhibitory activity against cytotoxicity in vivo, as well as in cell culture, and would be a good candidate for therapy of pseudomonal infections.

ADP Ribose Transferases↗
PubMed1992

[Adjuvant chemotherapy with MVP-CAB (methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin and bleomycin) for epithelial tumors of the upper urinary tract].

Surgery plus adjuvant chemotherapy using MVP-CAB (Day 1; methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg, Day 2; cisplatinum 50 mg/m2) was conducted in 12 patients with epithelial tumors of the upper urinary tract who had unfavorable prognostic factors (progressive disease which was pT2 or more, or transitional cell carcinoma of grade 2 and 3). The MVP-CAB regimen was as follows: A total of 3 cycles were given either before or after surgery. MVP-CAB was given at 3- to 4-week intervals before surgery, or after surgery if the patient had macroscopic residual lesions. For the patients with micrometastases detected after radical surgery, MVP-CAB was given every 1 to 2 months. The median survival period of the 10 patients who underwent radical surgery was 17 months (5-59 months). The three-year survival rate of these 10 patients (Kaplan-Meier method) was 100% in grade 2 (5 patients), 100% in progressive cancer greater than pT3 (6), and 80% in grade 3 (5). In two patients, residual macroscopic lesions after surgery were confirmed. One of them initially responded to MVP-CAB but died of cancer 21 months later, while the other one did not respond and died of cancer 8 months later. Two renal pelvis cancer patients for whom radical surgery was considered impossible due to distant metastases showed remarkable tumor reduction after MVP-CAB administration (one showed CR for liver metastases and the other showed PR for lymph node metastases).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Kock-rectal bladder. Augmented and valved rectum].

Eight patients with total cysto-urethrectomy underwent an augmented and valved rectum (Kock), a type of continent urinary diversion. A satisfactory outcome was obtained in 6 patients. These 6 patients urinated 6 to 8 times a day (1-2 times during the night). The volume each time was 350-450 ml. Urinary incontinence occurred only 1-2 times a month when deeply asleep, and there were no patients whose daily life was restricted. However, there were 3 patients with urinary tract complications. In 2 of them, urinary diversion was required, and unilateral total ureteral obstruction was observed in the remaining patient. The reason for the complications appeared to be that stapling of the intussusception of the sigmoid colon was performed in 5 placements as described in the original method. Following the 4th patient, we were able to prevent any complication in the urinary tract by stapling of the intussusception in 3 places (at 12, 5 and 7 o'clock), and by suturing mucosa to mucosa of the rectum and intussusception in 6 places with polyglycolic acid suture, and further suturing serosa to serosa of the sigmoid colon and rectum in 4 places with silk suture.

Aged↗
PubMed1992

[Adjuvant chemotherapy (MVP-CAB; methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin) for bladder cancer].

Twenty-three patients with bladder cancer (TCC; 18 patients, SCC; 5 patients) were treated with adjuvant chemotherapy (day 1: methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg, day 2: cisplatinum 50 mg/m2; MVP-CAB). A total of 3 cycles of MVP-CAB were given as preoperative or postoperative therapy. The following results were obtained. Group 1 (purpose to preserve the bladder, preoperative MVP-CAB): Four of 7 patients achieved a partial response. It was possible to perform bladder preservation surgery in 3 of these 4 patients. All 3 patients had pedunculated, solitary tumors, and there was no carcinoma in situ. Group 2 (purpose to improve the prognosis; preoperative MVP-CAB): Hydronephrosis did not resolve in the 4 patients with this complication. They received total cystectomy, and 2 patients died of cancer 23 months later. Group 3 (purpose to improve the prognosis; postoperative MVP-CAB): Ten of 12 patients (total cystectomy; 10 patients, partial cystectomy; 2 patients) survived disease-free for an average of 17 months (5-44 months), 1 patient developed recurrence 12 months later, and 1 patient died of cancer 6 months later. The 1-year survival rate in Group 3 was 86% for TCC, 100% for SCC, 80% for grade 3 TCC, and 89% for pT2 or more advanced cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Pneumothorax during laparoscopy].

A 28-year-old female was scheduled for laparoscopy under general anesthesia. Her history and physical examination were unremarkable. Trachea was intubated uneventfully following intravenous administration of thiopental 200 mg and vecuronium 8 mg. Anesthesia was maintained with 40% O2, 60% N2O and sevoflurane. Shortly after pneumoperitoneum was introduced, airway resistance increased and breathing sounds were hardly audible over the right side of the chest. A chest radiograph showed the right pneumothorax. Immediately after evacuating the peritoneal gas, the chest radiograph and a blood gas analysis showed that the pneumothorax had improved. Pneumothorax can occur subsequently to pneumoperitoneum due to passage of gas through weak points or defects in the diaphragm. Breathing sound should be monitored carefully during the laparoscopic surgery. Anesthetic gas analyzer and capnometer are considered to be useful to confirm the cause of the pneumothorax.

Adult↗
PubMed1992

HTLV-I associated gastric lymphoma.

A large gastric lymphoma was detected in a 42-year-old woman who was seropositive for HTLV-I. The tumor was histologically shown to be of diffuse large cell type, and phenotypic analysis revealed high expression of CD3 and CD4, indicative of a helper/inducer type of T-cell lymphoma. In Southern blot analyses, the tumor cells showed T-cell receptor re-arrangement and contained proviral DNA of HTLV-1.

Adult↗
PubMed1991

The carboxyl terminal amino acid residues of Pseudomonas aeruginosa exotoxin A involved in cell toxicity and pathogenesis, characterized by a neutralizing human monoclonal antibody.

Human monoclonal antibody HI-1A4 (IgG3, lambda) neutralized a toxicity caused by pseudomonal exotoxin A (Ex-A) in cell culture and in vivo, and was effective in experimental Pseudomonas aeruginosa infections in mice. HI-1A4 inhibited an Ex-A catalyzed ADP-ribosylation of elongation factor 2 but did not inhibit an incorporation of toxin into a target cell at all. One molecule of HI-1A4 neutralized at least 2 molecules of Ex-A. HI-1A4 retained its binding activity at pH 4.0. The epitope region for HI-1A4 was demonstrated to be a carboxyl terminal end of amino acid residues 591-613 of Ex-A. HI-1A4 might bind to Ex-A carboxyl terminal region outside a target cell, be incorporated into cells as a complex with Ex-A, and inhibit the intracellular function in which the carboxyl terminal part of Ex-A was involved, resulting in the interruption of intoxication of Ex-A.

3T3 Cells↗
PubMed1991

Kinetic control of steroidogenesis by steroid concentration in guinea pig adrenal microsomes.

For clarification of the effects of steroid concentration on steroidogenesis of adrenal microsomes, the kinetic parameters, Km and kcat, were determined in the steady-state for progesterone and 17 alpha-hydroxyprogesterone metabolism catalyzed by P-450C21 and P-450(17 alpha lyase) in guinea pig adrenal microsomes. At a high concentration of progesterone, it was equally metabolized by P-450C21 and P-450(17 alpha lyase), while at a low concentration, it was hydroxylated at 17 alpha-position with twice higher rate than at 21-position. 17 alpha-Hydroxyprogesterone is apparently metabolized preferentially by P-450C21 at any concentration. Although the productions of deoxycortisol and androstenedione from 17 alpha-hydroxyprogesterone were strongly inhibited by progesterone, androstenedione formation from progesterone was not inhibited by a high concentration of progesterone. The addition of liposomal P-450C21 to the reaction medium containing adrenal microsomes caused a decrease in the concentration of 17 alpha-hydroxyprogesterone released into the medium in the steady state reaction, but this had no effect on the activity of androstenedione formation from high concentrations of progesterone. It thus follows that androstenedione is produced by successive monooxygenase reactions without the release of 17 alpha-hydroxyprogesterone from P-450(17 alpha lyase) at a high concentration of progesterone, which is the condition of the adrenal microsomes in vivo.

17-alpha-Hydroxyprogesterone↗
PubMed1991

C3 deposition in IgA nephropathy in children and adolescents.

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5-21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1+ (N = 4): mesangiocapillary and 1+; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1+ (N = 18): mesangial 1+; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.

Adolescent↗
PubMed1991

C3 deposition in serially biopsied children with IgA nephropathy.

Twenty-five children with IgA nephropathy were studied by serial renal biopsy to investigate C3 deposition. The children were classified into three groups according to the immunofluorescent (IF) course of C3 deposition: group I (N = 9): unchanged or slightly decreased; group II (N = 4): changed to segmental deposition; and group III (N = 12): changed to negative deposition. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, adhesion, fibrous crescents and tubulo-interstitial change). The IF findings were scored semiquantitatively and laboratory data were also studied. The following results were obtained: 1. Normal urinalysis was often observed in group III; 2. The IF scores of IgA and IgG were decreased at the second biopsy in all groups, most notably in group III; 3. The activity indices at second biopsies were decreased in all groups, most notably in groups II and III, consistently with our previous study which showed that C3 deposition increases in accordance with histological activity; 4. The chronicity index was unchanged in all groups and C3 deposition did not reflect histological chronicity. Thus, this study indicates that C3 deposition occurs as the disease progresses and reflects histological activity.

Adolescent↗
PubMed1991

[Treatment of newly diagnosed stage D2 prostatic carcinoma with hormonal therapy alone, or chemotherapy agents in combination with hormones].

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

Administration, Oral↗
PubMed1991

[Combination chemotherapy with methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin (MVP-CAB) for metastatic urothelial cancer].

We studied 31 patients with bidimensionally measurable metastases of urothelial cancer who were treated with a planned regimen (20 mg/m2 methotrexate, 0.6 mg/m2 vincristine, 500 mg/m2 cyclophosphamide, 20 mg/m2 adriamycin, and 30 mg bleomycin on day 1, and 50 mg/m2 cisplatinum on day 2) in cycles given every 3 weeks. CR was achieved in 4 patients (13%) and PR in 17 patients (55%). The response rates according to the disease characteristics were 71% for TCC, 33% for SCC, 67% for renal pelvis tumors, 67% for bladder tumors, 73% for lung metastases, 67% for liver metastases, and 67% for lymph node metastases. The median response duration and the number of cycles of therapy were 32 months/3 cycles for patients with a CR and 6 months/6 cycles for those with a PR. The median duration of survival was 32 months (range: 3-46) in CR, 11 months (range: 1-37) in PR, and 6 months (range: 2-10) in non responders (NC + PD). A significant prolongation of survival was noted in patients with either CR (p less than 0.01) or PR (p less than 0.05). Then main toxic effects were pulmonary fibrosis and myelosuppression. Two patients aged 73 and 81 died of pulmonary fibrosis. However, it was possible to prevent pulmonary fibrosis by not administering bleomycin to patients over 70 years of age, or to patients with pulmonary dysfunction. WBC count nadirs of less than 2,000/m3 were noted in 22 patients (71%). Platelet count nadirs of greater than 5 x 10(4)/mm3 were noted in 7 patients (23%). However, there were no deaths due to myelosuppression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Benign polyp with prostatic-type epithelium of the urinary bladder: a case report.

We report a case of benign polyp with prostatic-type epithelium of the urinary bladder. A 58-year-old male presented with gross hematuria. Cystoscopic examination revealed a 2-mm polypoid lesion in the mid trigone. Immunohistochemical demonstration of prostatic acid phosphatase and prostatic specific antigen in the urothelial cells as well as the prostatic-type epithelial cells suggested the histogenesis of this polyp to be metaplasia of the urothelium.

Antigens, Neoplasm↗
PubMed1990

[Effects of human Cu, Zn-superoxide dismutase in aminonucleoside nephrosis--evaluation of the morphology and glomerular basement membrane anionic charge sites].

It was examined whether superoxide dismutase (SOD) had protective effects in puromycin aminonucleoside nephrosis (PAN). Nephrotic rats were induced by a single intraperitoneal injection of puromycin aminonucleoside (PA, 60 mg/kg). Subcutaneous administration of SOD (30 mg/kg) was started the day before PA injection and continued every 24 hours. Animals were sacrificed 10 days later to assess the morphology and glomerular basement membrane anionic charge sites (CSs). GBM CSs were stained in vitro with polyethyleneimine (PEI) and studied by electron microscopic examination. The SOD-injected group had a significant reduction of urinary protein excretion compared to the PA-treated group. Light microscopy revealed that vast majority of glomeruli in PA-treated group had segmental mesangial expansion and epithelial cell adhesions of the glomerular tuft to Bowman's capsule. Contrasted to these changes in the PA group, glomeruli from SOD-treated group showed less severe morphologic changes. On electron microscopy, the PA-treated rats exhibited marked glomerular epithelial loss of foot processes, epithelial attenuation, cytoplasmic vacuolization and protein reabsorption droplets. The SOD-treated animals demonstrated a lesser degree of epithelial loss of foot processes with a few protein reabsorption droplets. There was also a significant decrease in GBM lamina rara externa CSc stained with PEI in PAN compared to the control. The SOD-treated rats had a significant increase in GBM CSs compared to those of the PAN rats. SOD has protective effects in urinary protein excretion, the morphology and GBM CSc in PAN, which indicate indirect evidence that superoxide and/or its metabolites are responsible for glomerular injury.

Animals↗