Biomedical subjects
Publications and source records attributed to A Osawa.
The fundamentals of electrocardiographic diagnosis and the types of abnormal ECGs frequently found during surgery are described in this two-part article. Part 1 discusses lead placement and artifact recognition. Part 2 will describe arrhythmia and atrial fibrillation and flutter. Clinical situations of each are analyzed.
The molecular structure of the active site of myoglobin from the shark, Galeorhinus japonicus, has been studied by 1H-NMR. Some hyperfine-shifted amino acid proton resonances in the met-cyano form of G. japonicus myoglobin have been unambiguously assigned by the combined use of various two-dimensional NMR techniques; they were compared with the corresponding resonances in Physter catodon myoglobin. The orientations of ThrE10 and IleFG5 residues relative to the heme in G. japonicus met-cyano myoglobin were semiquantitatively estimated from the analysis of their shifts using the magnetic susceptibility tensor determined by a method called MATDUHM (magnetic anisotropy tensor determination utilizing heme methyls) [Yamamoto, Y., Nanai, N. & Chûjô, R. (1990) J. Chem. Soc., Chem. Commun., 1556-1557] and the results were compared with the crystal structure of P. catodon carbonmonoxy myoglobin [Hanson, J. C. & Schoenborn, B. P. (1981) J. Mol. Biol. 153, 117-124]. In spite of a substantial difference in shift between the corresponding amino acid proton resonances for the two proteins, the orientations of these amino acid residues relative to the heme in the active site of both myoglobins were found to be highly alike.
A questionnaire study was performed among 23,209 dialysis patients in 589 institutions together with a retrospective study at Keio University Hospital to determine the risk of malignancy and factors affecting the risk ratio in dialysis patients. The incidence and mortality were 1.4-fold and 1.9-fold higher in dialysis patients than the expected rates in the general population. Incidence and mortality were 1.9-fold and 2.6-fold higher in males than in females. The risk ratios were remarkably high in university hospitals, followed by public hospitals. However, there was no significant difference between those in private hospitals and in the general population. The incidence was very high during the first 6 months of dialysis treatment and rather low in the 7th-10th year. The risk ratio of malignancy was higher in younger patients. Beyond the age of 60, the influence of age was greater than that of renal failure. Malignancies of the digestive organs were frequent and constituted 56% of all malignancies. Frequencies of malignancy in the liver, colon, rectum, bladder and kidney were higher than expected, whereas in the pancreas the frequency was lower than expected. Metastasis of malignancy was observed in 30% of the cases. Our study demonstrated a slight to moderate overall increase in the risk of malignancy and a widely differing risk ratio of malignancy by organ involved, sex, age, hospital group, epidemiological index and length of dialysis treatment in a large single racial population of maintenance dialysis patients.
This paper describes methods of entering data into an expert system used to study lower urinary tract pressure and flow. Data is usually entered into an expert system directly from the keyboard or on an online basis. We have developed a new method of offline data entry using a photoscanner. For this method, we developed versatile software to convert the graphic data read by a photoscanner to online data format. This software allows us to handle graphic data printed on paper in the same way as online data. The software is also designed to solve the problems caused by blurred lines or ink spots on printed charts. In other words, the software compensates for data reading errors caused by blurred or stained lines on printed charts. Because data can be entered through the photoscanner, the enormous volume of data already recorded in graphic forms can be used by the expert system. As a result, the diagnostic capability of the expert system is significantly improved.
In vivo distribution of radiolabeled lymphokine-activated killer (LAK) cells that were administered either through the caudal vein or the abdominal aorta of Lewis rats was studied. The LAK traffic study showed remarkable increase in radioactivity in several organs peripheral to the arterial injection site. We began treating the patients with metastatic renal cancer by means of regional arterial administration of LAK cells. This treatment was supported by the results of the traffic assay. Our regional LAK therapy, which involves a weekly leukapheresis in combination with daily systemic low dose interleukin-2 administration, has been in practice for over 2.5 years. Seven out of 12 metastatic lesions in the 7 patients treated showed regression. Two responding cases have been alive for over 2 years. Responding lesions were bone, muscle, para-aortic lymph node, and/or retroperitoneum. The regional arterial administration of LAK cells is local therapy. However, this mode of therapy could be useful for those patients with extrapulmonary nonresectable metastasis and at least one injectable feeding artery. This study shows our laboratory data concerning the localization of LAK cells transferred via arterial route and our clinical cases treated with regional arterial administration of LAK cells.
An elderly case of idiopathic retroperitoneal fibrosis (IRPF) with bilateral ureteral obstruction was reported. A 74-year-old man was admitted with complaints of general fatigue and loss of appetite. An elastic hard mass with a smooth surface was palpated in the left upper quadrant of the abdomen. Abnormal ESR and CRP were noticed. Abdominal ultrasonography showed both a homoechoic mass which surrounded the aorta in the retroperitoneal space and bilateral hydronephrosis. Computed tomography revealed a retroperitoneal mass involving bilateral ureters. Magnetic resonance imaging demonstrated a mass with a sharp image and signal intensity. Furthermore the morphological relationship between the mass and the ureters and major vessels clearly indicated the characteristics of benign retroperitoneal fibrosis. Based upon the above findings, a diagnosis of IRPF was made. After confirming the histological diagnosis by biopsy, treatment consisting of bilateral ureterolysis, intra-abdominal transposition of ureters and oral administration of prednisolone was performed, resulting in a normalization of laboratory findings. Analysis of 86 previously cases of IRPF reported up to 1990 in Japan, revealed the peak age to be in the 7th decade with predominance in males (males: females = 57:29).
A case of eosinophilic cystitis complicated with transient vesicoureteral reflux in an 11-year-old girl with allergic disorders is reported. She was suffering from pollakisuria, painful urination, vesical irritability, and gross hematuria for about 2 months. Urinalysis showed aseptic pyuria. White blood cell count was 9,700/mm3 with eosinophils of 10%. Eosinophils were also found on urine cytology. Intravenous pyelography revealed bilateral hydronephrosis and apparently contracted bladder. Tumorous lesion and edematous mucosa were observed in the retrotrigonal region on cystoscopy. The multiple bladder biopsy uniformly revealed eosinophilic cystitis. Following antiallergic treatment, practically all symptoms subsided in steps, and normal cystoscopic appearance and histological structure were restored in 3 months. The vesicoureteral reflux markedly diminished in 10 months.
The ferric high-spin form of the myoglobin from the shark Galeorhinus japonicus, which possesses a Gln residue at the distal site instead of the usual His residue, has been studied by 1H-NMR spectroscopy. Using the heme meso-proton (C5H, C10H, C15H and C20H) resonance shift as a diagnostic probe for identifying the coordination system of the iron center in ferric high-spin form of hemoprotein, it has been shown that G. japonicus metmyoglobin (metMb) possesses the pentacoordinated active site. The pH-dependence study of NMR spectra of G. japonicus metMb revealed the appearance of the hydroxyl form of metMb at high pH, indicating that the protein undergoes the transition between the acidic and alkaline forms. The pK value and the rate for this acid-alkaline transition in G. japonicus metMb were found to be approximately 10 and much less than 4 x 10(2) s-1, respectively. Since the pK value of the acid-alkaline transition for the pentacoordinated heme in Aplysia limacina metMb is 7.8 [Giacometti, G.M., Das Ros, A., Antonini, E. & Brunori, M. (1975) Biochemistry 14, 1584-1588] and that of the hexacoordinated heme in sperm whale metMb is 9.1 [Brunori, M., Antonini, E., Fasella, P., Wyman, J. & Rossi-Fanelli, A. (1968) J. Mol. Biol. 34, 497-504], the OH- affinity of the ferric heme iron does not appear to depend on its coordination system. The acid-alkaline transition rate in A. limacina metMb was reported to be much less than 1.5 x 10(2) s-1 [Pande, U., La Mar, G.N., Lecomte, J.T.J., Ascoli, F., Brunori, M., Smith, K.M., Pandey, R.K., Parish, D.W. & Thanabal, V. (1986) Biochemistry 25, 5638-5646] and therefore a slow transition rate may be unique to the pentacoordinated active site of Mb.
Human autologous peripheral blood lymphocytes (PBL) and lymphocytes infiltrating renal cell carcinoma (TIL) were cultured with medium containing 1000 IU/ml of human interleukin 2 (IL-2). A high cytotoxic activity against fresh autologous as well as cultured allogenic tumor cells was developed. By culturing these lymphocytes with OKT3 monoclonal antibody during the initial 2 days of long-term culture, in terms of T cell activation signal, IL-2-driven lymphocyte proliferation was remarkably accelerated with maintenance of appreciable level of cytotoxic activity. The same culture method also induced an increase in OKT3 and IL-2 receptor positive lymphocyte population in LAK cells and TIL. This method may enable us to gain more autologous TIL in vitro for adoptive immunotherapy of renal cell carcinoma than the usual culture method with IL-2 alone. Five patients with metastatic renal cell carcinoma were treated with adoptive immunotherapy with TIL, LAK and IL-2. One patient with pulmonary metastasis has had a minor response which has lasted for 3 months so far. We have not experienced any serious side effects during the treatment.
Immunological studies were performed in 87 patients with chyluria referred to our clinic from January 1982 to December 1988. White blood cell count in 78 patients was 5210.3 +/- 1440.9/mm3. The fraction and the number of lymphocyte were 18.7 +/- 9.5% and 934.1 +/- 521.6/mm3, respectively: they were lower than normal limit. The percentages of T and B lymphocytes studied in 46 patients were 79.3% +/- 11.2% (normal range: 76-86) and 10.4 +/- 7.9% (normal range: 8-16), respectively: both lymphocytes tended to decrease in percentage. Lymphocyte blast formation stimulated with phytohemagglutinin (PHA) was carried out in 20 patients. The mean of the blast formation was 17410.0 +/- 10275.1 c.p.m. (normal range: 377700-62400), and much lower than normal value. Of 22 patients who had PPD skin test, only 9 (40.9%) were positive. These findings signified that cellular immunity was suppressed in patients with chyluria. On the other hand, the value of immunoglobulin was within normal range (IgG: 1325.3 +/- 475.6 mg/dl, IgA: 242.0 +/- 98.3 mg/dl, IgM 130.4 +/- 95.9 mg/dl). Study on the values of laboratory examinations showed statistically positive correlation between total lymphocyte population and T cell number, and between total lymphocyte population and lymphocyte blast formation. In patients with chyluria, serious sequelae have not been reported. However, care should be taken for possible opportunistic infection and, particularly, malignant tumors because suppression of cellular immunity may be one of the promoting factors of malignant tumors.
From March, 1986 through June, 1988, the reduced M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was used to treat 6 patients with metastatic or locally invasive transitional cell carcinoma of renal pelvis and ureter. Out of 5 evaluable patients with advanced stages (N+ and/or M+) pathological complete remission and partial remission were observed in one patient each and minor remission in two patients inspite of our reduced regimen according to performance status of the patients. Toxicity was rather mild except in one patient who showed severe myelosuppression. This regimen seems to give favorable antitumor activity against transitional cell carcinoma of upper urothelium.
2D NMR spectroscopies have been successfully used to characterize the heme peripheral vinyl groups in paramagnetic hemoprotein in spite of the difficulties from the rapid paramagnetic relaxation and the low digital resolution of the 2D NMR map. The scalar coupling network system among the vinyl protons is clearly identified in the COSY spectra from its characteristic cross-peak pattern and the dipolar coupling connectivities of the vinyl proton resonances with other heme side-chain proton resonances not only provide the specific assignment of vinyl beta-proton resonances but also allow the determination of the vinyl group orientation with respect to the heme plane.
A 3-year-old boy underwent an operation for a right undescended testis. A small, elastic, hard mass attached loosely to the spermatic cord was noted in the inguinal canal away from the testis and epididymis. Pathological examination of this mass revealed mesonephric remnant tissue.
Fifty eight patients who underwent ileal conduit formation in our hospital for the past 14 years were reviewed. Out of them, 11 patients developed hydronephrosis which should be treated. It occurred due to urolithiasis, recurrent tumor, contracted ileal loop in one patient respectively, and ureteroileal junction stricture in 8 patients (10 ureteral units). The 8 patients consisted of 6 males and 2 females. All of the males underwent total cystectomy because of bladder tumor (T.C.C.), and the females had anterior pelvic exenteration because of uterine cancer (adenocarcinoma). Out of 10 ureteral units, 7 were corrected by surgical intervention, 1 was dilated with endourological procedure, and 2 had no treatment. Six ureteral units including 1 ureteral unit treated by an endourological method resulted in improvement or disappearance of hydronephrosis. Histological examination of the stricture revealed fibrosis in 7 ureteral units treated surgically. According to our clinical studies, infection in the pelvic space seemed to be one of the causes which brought about ureteroileal junction stricture.
We herein report the preliminary but appreciable results of regional transarterial infusion of 2 gravity subtypes of autologous lymphokine-activated killer (LAK) cells into the metastatic sites in combination with systemic recombinant interleukin-2 (rIL-2) administration in 3 patients with advanced renal cell carcinoma. Leukapheresis was performed once a week and peripheral blood lymphocytes were separated into 2 different subtypes by Percoll gradient centrifugation. These lymphocytes were incubated with rIL-2 for a few days to induce LAK cells. LAK cells were transferred to the metastatic lesions through cannula twice a week. A large iliac bone metastasis disappeared 3 months after the initial LAK cell therapy via a superior gluteal artery. A case of complete disappearance of psoas muscle and para-aortic lymphnode metastasis as well as partial regression of a lumbar bone metastasis was seen after lumbar arterial infusion treatment. Another case with brain metastasis showed a rapid exacerbation of brain edema after one week's LAK therapy. Our treatment modality seems to be worthwhile and promising for treatment of the advanced renal cell carcinoma.
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Prognosis on evaluable 86 patients with primary bladder tumor seen during the 10 years up to 1985 was evaluated in relation to treatment mode and tumor stage. The majority of patients underwent multimodal therapies including surgery, chemotherapy and immunotherapy with picibanil (OK432). Transurethral resection of the tumor was performed as an initial surgical treatment in 49 patients, 9 of whom ultimately underwent total cystectomy. After leaving hospital, these patients were kept on immunotherapy with OK432 and topical chemotherapy with bladder instillation of mitomycin C or adriamycin (ADM) with or without systemic administration of Tegefur as long as possible. The overall actual 5-year survival rate for the patients treated by initial transurethral resection was 80%. Recurrence rate for these 49 patients was 35%. Total cystectomy with urinary diversion was performed in 37 patients who had been placed postoperatively on systemic administration of Tegafur and immunotherapy with OK 432 as long as possible. The overall actual 5-year survival rate for the patients treated with total cystectomy was 54%. The patients with pT2 and lower stage tumor had an actual 5 year survival rate of 72%, while the patients with pT3 and higher stage tumors had a survival of 10%. The high recurrence rate in the patients with superficial tumor and the low actual survival rate of the patients with pT3 and higher stage remain a problem in the treatment of bladder tumor. In recent trials, bacillus Calmette-Gúerin instillation therapy has been initiated to lower the recurrence rate in superficial tumor and we have had a satisfactory 4-year result.(ABSTRACT TRUNCATED AT 250 WORDS)