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Biomedical subjects

A Higuchi

Publications and source records attributed to A Higuchi.

At least 73 records · Page 4Linked to original sources
PubMed1993

Protective activity of anti-exotoxin A monoclonal antibody against mice infected with toxin-producing Pseudomonas aeruginosa.

The neutralizing and protective effect of murine monoclonal antibody (MAb) 3C7 (IgG1) against Pseudomonas aeruginosa exotoxin A was examined in an experimental mouse model of infection with exotoxin A-producing strains. Treatment with MAb 3C7 blocked the reduction of functional elongation factor 2 (EF-2) in the liver of mice but could not clear the bacteria. Administration of gentamicin caused bacteria to be cleared but did not block reduction of hepatic EF-2 level. Treatment with either MAb 3C7 or gentamicin individually did not prolong time to death; however, the combined therapy with both MAb 3C7 and gentamicin cleared bacteria and blocked the reduction of hepatic EF-2 level, resulting in a significant increase in the survival rate of mice. These results suggest that anti-exotoxin A MAbs show effectiveness against pseudomonal infection caused by exotoxin A-producing strains.

ADP Ribose Transferases↗
PubMed1993

Adjuvant chemotherapy for invasive urothelial cancer: experience with a methotrexate, vincristine, cisplatin, cyclophosphamide, adriamycin and bleomycin (MVP-CAB) regimen: a preliminary report.

MVP-CAB chemotherapy (methotrexate, vincristine, cisplatin, cyclophosphamide, adriamycin and bleomycin) was administered to 28 patients with high grade, locally-invasive or regional lymph node-involved urothelial cancer as an adjuvant therapy after radical surgery. The median follow-up period of all the evaluated patients was 24 (range, 5-62) months. The median disease-free durations in patients with pT1b+2+3 bladder and upper urothelial cancer were 26 and 22 months, respectively. In contrast, all patients with pT4 disease or lymph node metastases had a recurrence within 24 months of surgery. The median disease-free durations in patients with pure transitional cell carcinoma (grade 3) of the bladder and upper urothelial cancer were 19 and 18 months, respectively. The median disease-free duration in patients with grade 3 pT1b+2+3 pure transitional cell carcinoma was 19 months. In contrast, the median disease-free duration in bladder cancer patients with pT1b+2+3 squamous cell carcinoma components was 35 months. The three-year actuarial survival rates were 79 and 89% for pT1b+2+3 bladder and upper urothelial cancer, respectively, while the three-year actuarial survival rates of patients with pT4 bladder cancer and pT4 upper urothelial cancer were 0 and 100%, respectively. The two-year actuarial survivals in the bladder cancer and upper urothelial cancer patients with lymph node involvement were 0 and 100%, respectively. The three-year actuarial survivals of patients with pure transitional cell carcinoma (grade 3) were 53 and 80% in bladder cancer and upper urothelial cancer patients, respectively. The three-year actuarial survival rate in patients with squamous cell carcinoma or adenocarcinoma components which did not recur was, however, 100%. Although randomized studies comparing MVP-CAB and M-VAC (methotrexate, vinblastin, adriamycin and cisplatin) or other chemotherapeutic regimens will be necessary, we believe our results indicate that MVP-CAB chemotherapy may be useful as an adjuvant therapy for patients with urothelial cancer, including those with squamous cell carcinoma and adenocarcinoma components. More intensive MVP-CAB chemotherapy, i.e., increasing the dose of cisplatin and giving at least five courses, as well as the use of granulocyte colony stimulating factor and a new antiemetic drug (granisetron), will, however, be necessary for patients with pT4 or lymph node-involved disease.

Adenocarcinoma↗
PubMed1993

Paratesticular leiomyosarcoma with elevated serum basic fetoprotein: a case report.

A case of paratesticular leiomyosarcoma associated with elevated serum basic fetoprotein level is reported. A 45-year-old male visited our hospital with a 6-month history of a painless left scrotal mass. High orchiectomy was performed under the diagnosis of left testicular tumor. Macroscopic and microscopic examination of the resected tumor demonstrated it to be paratesticular leiomyosarcoma. The value of serum basic fetoprotein, which is a newly identified oncofetal protein and useful as a tumor marker in some kinds of malignant neoplasm, was elevated before therapy, and its fluctuation was correlated with his clinical course. In spite of chemotherapy and resection of metastatic lesions in the lung, his condition gradually deteriorate with increasing serum basic fetoprotein level, and he died with carcinomatosis 2 years and 6 months after his admission. We suggest that basic fetoprotein is a useful tumor marker in this disease.

Antigens, Neoplasm↗
PubMed1993

[A case of asynchronous renal cell carcinoma and urothelial cancer of the urinary bladder and left ureter].

A 49-year-old male with left renal cell carcinoma and urothelial cancer (bladder and residual left ureter), which asynchronously occurred, was reported. He had received radical nephrectomy due to renal cell carcinoma 12 years earlier. He was followed up by his local physician for 7 years postoperatively, during which time no metastatic lesion was detected. However, he presented with macroscopic hematuria on January 7, 1992, and a diagnosis of urinary bladder cancer was made at our hospital. Computerized tomography demonstrated a non-papillary, broad-based tumor on the left wall of the urinary bladder, which histologically was transitional cell carcinoma (grade 3). Radical cystectomy, ureterectomy of the left residual ureter and ileal conduit were performed. Histological examinations showed that the urinary bladder tumor was transitional cell carcinoma, grade 3, pT-3b, and CIS (transitional cell carcinoma, grade 3) was found in the residual left ureter. Chemotherapy containing cis-platinum was performed as an adjuvant therapy, but multiple lung metastatic lesions appeared 2 months postoperatively, the histology of which was transitional cell carcinoma, suggesting metastasis from the urothelial cancer. Chemotherapy was ineffective, and he died of the disease 9 months after the operation. If this patient had been under long-term follow-up, the urothelial cancer may have been resected completely by transurethral resection. Our report indicated the importance of examination of the urinary tract in patients with such cancers, as well as the necessity of long-term follow-up.

Carcinoma, Renal Cell↗
PubMed1993

[Anesthesia for severely burned patients--23 operations in 8 burned patients].

Severely burned patients require repeated debridement or skin grafting soon after the burn injury until the closure of the injury. We retrospectively examined 23 operations in 8 severely burned patients who had undergone debridement or skin grafting more than twice within 30 days. We classified 23 operations into 1st to 4th categories according to days after the burn injury and compared each group regarding intraoperative fluid balance, hypovolemia and perioperative complications. In the 3rd or 4th operation, mean blood loss and fluid administration were more than those of the 1st or 2nd operation. Respiratory dysfunctions or circulatory complications such as hypotension, oliguria occurred more frequently during or after the 3rd or 4th operation. Since patients are in hyperdynamic and hypercatabolic state at the time of the 3rd or 4th operation patients, they will be easily damaged in the peri-operative period. This study suggests that we should bear in mind, in the anesthetic management of burned patients, that they can be in hyperdynamic state as well as in shock state.

Adult↗
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↗