UCT1072s, new antitumor antibiotics with topoisomerase II mediated DNA cleavage activity, from Aspergillus sp.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Nakano.
Explore the source record for details and available documents.
BACKGROUND: We have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response. METHODS: Sixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringer's lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation. RESULTS: The serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A. CONCLUSIONS: We have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.
Explore the source record for details and available documents.
A 51-year-old man was admitted with systemic lymph node adenopathy. Hematological examination on admission revealed leukocytosis, and 35% of leukocytes were classified as pathologically abnormal. Moreover, increases in serum IgM (kappa type) and plasma viscosity were recognized. Following biopsy of the lymph node, a diagnosis of non-Hodgkin's lymphoma (diffuse, mixed type) was made. After the implementation of combination chemotherapy, the results of hematological and physical examinations improved. As the nadir receded, serum IgM increased once more, and nine courses of chemotherapy were necessary. In order to promote steady progress toward discharge, etoposide therapy was instituted. Subsequent low-dose etoposide therapy at 50 mg/day rarely resulted in an increase in serum IgM, subjective or objective adverse effects, except for mild lekopenia. After discharge the patient was placed on intermittent etoposide therapy and remained in a state of remission for approximately 11 months. Fortunately, his rehabilitation was successful, and he returned temporarily to his former position. The 2nd remission has continued for approximately seven months. Consequently, long-term low-dose etoposide therapy is speculated to be a significantly useful therapeutic technique for intractable malignant lymphoma.
BACKGROUND: Lymph node metastasis has been one of the strongest prognostic factors in patients with cervical cancer. In order to select patients with high risk for recurrence, a relationship between status of lymph node and other histopathological parameters was investigated in the patients treated with radical hysterectomy with pelvic lymph adnectomy. METHODS: Of 483 patients undergoing radical hysterectomy with pelvic lymph adnectomy, 309 had stage Ib disease, 62 stage IIa, and 112 stage IIb. RESULTS: Pelvic lymph node metastasis(PLNM) was positive in 98 patients (20%). Of those positive patients, 51(56%) had metastasis in one site, 25 (26%) in two sites, and 22 (22%) in three or more sites. There was a significant difference in survival between patients with metastasis in one or no sites and those in two or more sites (p<0.0001). There was a relationship between PLNM in more than two sites and histological parameters such as histologic subtype, longitudinal diameter of cervical lesion, degree of stromal invasion, depth of stromal invasion, lymph-vascular space invasion, parametrial invasion, and corpus invasion. All of these parameters except for histologic subtype were significantly correlated with the number of positive lymph node sites. Multivariate analysis revealed that among these parameters, longitudinal diameter of the cervical lesion, parametrial invasion, and lymph-vascular space invasion were independently significantly correlated with PLNM in two or more sites. CONCLUSIONS: From these results, patients having these three histopathological parameters could be considered as those with extensive disease distribution.
MOLT-4 cells undergo apoptosis after X irradiation. A radiosensitive variant, MOLT-4N1, and a radioresistant variant, MOLT-4N2, have been studied with respect to their radiosensitivity and its relationship to the levels of TP53 protein (formerly known as p53). X irradiation induces apoptosis in both cell lines with the following difference: The induction of apoptosis in MOLT-4N2 cells occurred later than in MOLT-4N1 cells as determined by the morphological changes and DNA fragmentation. The levels of cell death measured by the dye exclusion test coincided with the levels of apoptosis in both cell lines, suggesting that radiation-induced cell killing is determined by the induction of apoptosis. Unirradiated MOLT-4N1 cells contained a significantly higher intracellular level of TP53 protein and a much higher level of TP53 mRNA compared to MOLT-4N2 cells. X irradiation led to an accumulation of TP53 protein in both cell lines that was greater in MOLT-4N1 cells. This accumulation of TP53 protein preceded changes in DNA degradation and ladder formation and in nuclear morphology. These results strongly suggest that the radiosensitivity of MOLT-4 cells correlates well with the unirradiated control levels of TP53 mRNA and TP53 protein, and that the quantitative levels of TP53 protein must reach a threshold for the cells to undergo apoptosis.
We previously established (K. Sonoda et al., Int. J. Oncol., 6: 1099-1104, 1995) a novel monoclonal antibody, 22-1-1, generated from adenocarcinoma of the uterine cervix, and 22-1-1 antigen (Ag) was expressed in cancer cells derived mainly from the uterus and ovary. In this report, a relationship between 22-1-1 Ag expression and clinicopathological variables and the prognostic significance of 22-1-1 Ag were immunohistochemically investigated in adenocarcinoma of the cervix. Of 56 cases, the 22-1-1 Ag was negative in 7, 1+ in 14, 2+ in 26 and 3+ in 9 instances. The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. There was no correlation between 22-1-1 Ag expression and age, stage, grade, myometrial invasion, lymph-vascular space invasion, lymph node metastasis, and parametrial invasion. The estimated 5-year overall survival (OS) of patients with low 22-1-1 Ag expression (-/+) and high 22-1-1 Ag expression (++/ ) were 90.5 and 71.4%, respectively. Patients with high 22-1-1 Ag expression had significantly worse OS than those with low 22-1-1 Ag expression (log-rank test, P = 0.0193). In addition, lymph-node metastasis, age, and clinical stage were significantly related to OS in univariate analysis. Multivariate analysis for OS revealed a prognostic significance in 22-1-1 Ag expression, stage, age, and grade. These data suggest that 22-1-1 Ag expression may be related to prognosis in adenocarcinoma of the cervix.
A 63-year-old man was admitted to our hospital because of left back pain and dysesthesia in his left arm. On physical examination, the patient had ptosis, myosis, and anhydrosis on the left side, suggesting Horner's syndrome. A chest computed tomographic scan disclosed a mass lesion adjoining to the left posterior mediastinum. Although the mass lesion showed a slight decrease in size after the systemic administration of corticosteroids, no further improvement was obtained. Open chest examination revealed extended thickening of the parietal pleura with massive involvement of the upper thoracic sympathetic trunk. The diagnosis was malignant mesothelioma of sarcomatous type. Horner's syndrome is a rare but possible complication in the clinical course of malignant pleural mesothelioma.
Sleep fragmentation is considered to have a central role in the pathophysiology of sleep-disordered breathing. However, the evaluation of sleep fragmentation can be very troublesome work. We sought to evaluate sleep fragmentation in 10 patients with obstructive sleep apnea syndrome by utilizing fast-fourier transforms to render their sleep encephalograms as spectrograms (horizontal axis: time, vertical axis: frequency, color: power). Detailed 5-minute spectrograms revealed relatively uniform patterns of change in EEG spectra during and after apnea episodes. In non-REM sleep, delta activity during apnea was followed by alpha and beta activity during resumed breathing. In REM sleep, flat and low-power spectral patterns during apnea were followed by relatively weak alpha and beta activity during resumed breathing. In compressed, 1-hour views of the spectrograms, repeated apnea events appeared as vertical striped patterns of spectral change. These patterns were thought to be representative of sleep fragmentation. The spectrographic display of EEGs may be a very simple and easy method for the evaluation of sleep-fragmentation in sleep disordered breathing.
The recently discovered GB virus C/hepatitis G virus (GBV-C/HGV) has been shown to be scarcely associated with hepatitis, though its possible pathogenesis remains unknown. In previous report, we designed primers for semi-nested reverse transcription-polymerase chain reaction (RT-PCR) to detect 5'-noncoding region of GBV-C/HGV, and screened the sera from 45 patients with liver diseases or on hemodialysis. In this study, we studied the prevalence of GBV-C/HGV infection in the sera from 35 patients with hemophilia A by this RT-PCR method, and also performed sequence analysis for all isolates including those from the non-hemophilic patients previously reported. GBV-C/HGV was detected in 8.57% (3/35) of the hemophilic patients. The isolates from hemophilic patients had several common mutations, and these mutations were also common in the "West African" genotype isolates represented by the prototype GBV-C. However, sequences in the isolates from other positive patients with liver diseases or on hemodialysis were quite different from those in the isolates from hemophilic patients, and those in the "European/American" genotype isolates represented by the prototype HGV. These sequences were consistent with "Asian" genotype. Simple restriction fragment length polymorphism (RFLP) analysis using the restriction enzyme HhaI successfully discriminated these genotypes. In the hemophilic patients, GBV-C/HGV might have been transmitted by transfusions of the imported plasma-derived clotting factor concentrates. Thus the difference in GBV-C/HGV genotype between the hemophilic patients and the others is suggested to be related to transmission route.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Segmental colitis which showed the similar findings of ulcerative colitis and right-sided colitis with back-wash ileitis has been considered as the unusual form of ulcerative colitis. Today, we have few opportunities to come across those cases, because modern diagnosis of colon disease could make differential diagnosis easily with the sense of broad spectrum of IBD. We presented three cases of segmental colitis and one case of so-called indeterminate colitis associated of carcinoma in the cecum and discussed the clinical significance for diagnosis and finding the step of studying the etiology of IBD. Especially, in the third case, thirteen years old man was showing the sign of early stage of Crohn disease with non-caseating granuloma in the biopsy specimen at first, the findings of the segmental ulcerative colitis with crypt abscess were seen after six months in the second examination. To observe the detail changes of the mucosal lesion in this kind of cases will present the new idea for studying the etiology of IBD.
The application of Doppler velocimetry in the evaluation of the normal human fetal circulation targeting organs such as the placenta, the liver, the brain, and the lungs is presented. Conditions wherein evaluation of the fetal circulation becomes important are many. These conditions include, but are not limited to, intrauterine growth retardation, fetal hydrops, and multiple gestation. The importance of combining Doppler velocimetry with M-mode echocardiography and B-mode scanning is also addressed.
We report a successful surgical case of billowing mitral leaflet syndrome combined with severe mitral regurgitation. A 45-year-old man suffered from congestive heart failure and admitted our institution for precise examination. A heart murmur was pointed out by a medical examination at his high school, and mitral valve prolapse was detected by echocardiography at 23 year of age. No medication was applied because he showed no symptom. From 44 year of age, he noted palpitation on exercise. Holter monitor showed blocked PAC and Wenckebach A-V block, and transesophageal echocardiography indicated severe mitral regurgitation due to the billowing of voluminous both leaflets. At his operation, we recognized the billowing of both leaflets with torn chordae, and size of the mitral valve orifice was 8.5 x 5 cm. The huge mitral valve was replaced with a CarboMedics 31M prosthetic valve by plicating mattress stitches of native mitral annulus. Histopathologic findings showed accumulation of acid mucopolysaccharide. Postoperative echocardiography showed reduction of the left ventricular volume and preservation of the left ventricular function. Relatively slow progression of the billowing mitral leaflet syndrome did not cause apparent symptoms of heart failure in this patient. Therefore, proper selection of the procedure and timing of surgical treatments might be important for successful long-term results after operation of the billowing mitral leaflet syndrome.
A 50-year-old female was admitted to a local hospital because of dyspnea, and diagnosed as having left heart failure secondary to mitral regurgitation. After the improvement of congestive heart failure, polyarthralgia, fever, and positive anti-nuclear antibody were pointed out. She was referred to our hospital for the further evaluation. Serological test showed anti-double stranded DNA antibodies, anti-SS-A antibodies, anti-beta 2-GPI antibodies and biological false positive for syphilis. The diagnosis of SLE has been made from the clinical signs and the serology. Therefore mitral valvular lesion of this patient was considered to be one of the symptoms of SLE. We reported a rare case in which left heart failure was a initial clinical manifestation of SLE.
A 79-year-old woman was admitted to our hospital with complaints of wheezing and dyspnea. Adenoid cystic carcinoma was diagnosed from the findings on biopsy specimens obtained by fiberoptic bronchoscopy. The tumor was resected and end-to-end anastomosis was performed. Precision analyses of lung sounds were conducted before and after the operation. During eupnea the tracheal sounds prior to operation contained an accentuated, high-frequency component at about 1,500 Hz. The tracheal sounds included a single monophonic wheeze during deep inspiration and 5 wheezes during forced expiration. By contrast, lung sounds in the chest wall were almost normal both before and after the operation. We concluded that increases in high-frequency components in tracheal sounds and the manifestation of various wheezes can be useful in diagnosing tracheal stenosis and/or tumors.