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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 289 records · Page 16Linked to original sources

Detection of a circulating tumor-associated antigen with a murine monoclonal antibody, LISA 101, selected by reversed indirect enzyme-linked immunosorbent assay.

In the presence of a characterized monoclonal antibody recognizing a soluble molecule, additional monoclonal antibodies reactive with unknown antigenic determinants on the molecule can be easily selected by reversed indirect enzyme-linked immunosorbent assay. A novel murine monoclonal antibody, LISA 101, was selected by reversed indirect enzyme-linked immunosorbent assay against soluble antigens, which exist in sera and in pleural effusions derived from lung adenocarcinoma patients and which bear determinants recognized by the previously characterized murine monoclonal antibody KL-6. Antigenic determinants recognized by the LISA 101 antibody appear to be sialylated carbohydrate in nature and different from those recognized by previously reported monoclonal antibodies against sialylated carbohydrates, such as NS 19-9, FH-6, and KL-6, suggested by competitive inhibition assay and immunostaining of tissues. A circulating antigen, LISA 1-6, was detected by a bimonoclonal bideterminant assay using immobilized LISA 101 antibody and enzyme-labeled KL-6 antibody. It was found that serum LISA 1-6 levels were elevated in 63% (25 of 40) of patients with lung adenocarcinoma and in 92% (11 of 12) of patients with pancreatic carcinoma, but only in 6.5% (2 of 31) of patients with benign lung diseases and in 7.1% (1 of 14) of patients with pancreatitis. The present observations indicate that the LISA 1-6 antigen may serve as a new tumor marker for adenocarcinomas of the lung and the pancreas. Additionally, the reversed indirect enzyme-linked immunosorbent assay may be a widely applicable method for selecting new monoclonal antibodies against as yet unknown antigenic determinants on soluble molecules.

Adenocarcinoma↗

[Ultrasonographic diagnosis of mild fatty infiltration of the liver with the difference between liver and kidney echolevels].

At the same dynamic range (DR) a constant difference of echolevels was found between two materials with different acoustic impedance in any gain-setting by the phantom study. Our retrospective study in which we compared the difference between liver-kidney echolevels with the US-findings of fatty liver indicated that the difference over 10 in echoleveled by our equipment with 3.5 MHz phased array sector scan and 42 dB DR had a possibility of the fatty infiltration of the live. In our prospective study of 1452 abdominal US-studies we found 93 cases (6.5%) with the difference over 10 in echolevel. In all these patients the difference of liver-spleen CT-numbers and liver-kidney echolevels was compared. Although the liver CT-number is normally higher than the spleen, 75 of 93 patients showed the lower liver CT-number than that of the spleen, indicating fatty infiltration of the liver. The abnormal difference of echolevels were independent from the severity of fatty infiltration. Concerning the US-findings, "bright liver" (77.4%) and "masking sign" (66.7%) were more sensitive than "vascular blurring" (44.1%) and "deep attenuation" (44.1%). But for the severe fatty infiltration with the difference over -20 H.U. between liver-spleen CT numbers, the last two findings seemed very credible. The abnormal difference between liver-kidney echolevels was most sensitive (80.7%), especially in mild cases with 0 to -19 H.U. (53 in 75 cases), and very objective than the other US-findings.

Fatty Liver↗

Allo-class I-reactive CD4-CD8- T cell hybridomas recognize the conformational change of class I molecule resulting from the exchange of the alpha 3 domain.

H-2Kb-reactive, interleukin (IL) 2-producing T cell hybridomas possessing neither CD8 nor CD4 molecules were employed for the study of allorecognition on interspecies hybrid antigens by T cells in the absence of an influence of these accessory molecules. Both HTB176.10 and HTB177.2 T cell hybridomas reacted with KbKbB7 hybrid antigens as well as Kb antigens and they produced more IL2 in response to Kb antigens than KbKbB7 hybrid antigens. IL2 production of these T cell hybridomas was dependent on the surface expression level of Kb molecules on stimulators. Therefore, L cells expressing almost equivalent levels of Kb or hybrid antigens were selected for further functional studies by these T cell hybridomas. They apparently produced less IL2 in response not only to interspecies hybrid antigens but also to interspecies hybrid antigens in response to Kb antigens. These results indicated that T cell hybridomas recognized the conformational change of class I molecule resulting from the exchange of the alpha 3 domain via their T cell receptors.

Amino Acid Sequence↗

The structure of HLA-B35 suggests that it is derived from HLA-Bw58 by two genetic mechanisms.

The primary structure of HLA-B51 and HLA-Bw52 suggested that HLA-B51 was derived from HLA-Bw52 by the combination of a genetic exchange with HLA-B8 and a point mutation. To investigate the evolution of the HLA-B5 cross reactive group, the HLA-B35 gene was cloned and the primary structure was determined. HLA-B35 is identical to HLA-Bw58 except in the alpha 1 domain. The alpha 1 domain of HLA-B35 except Bw4/Bw6-associated amino acids is identical to that of HLA-B51, which was suspected to be an intermediate gene between HLA-B51 and HLA-Bw52. These data suggest that HLA-B35 has evolved from HLA-Bw58 in two steps; an in vivo replacement of the alpha 1 domain with HLA-B51 and genetic exchange with one of the HLA-Bw6 genes. These three genes and HLA-Bw58 are postulated to share a common ancestor. As HLA class I molecules of a serologically cross-reactive group (CREG) have limited polymorphism, we suspected they might have evolved from a common ancestor. In fact, the structures of HLA-B51 and HLA-Bw52 in HLA-B5 CREG demonstrate that they differ by only two amino acids. Both substitutions are in the helical region of the alpha 1 domain and suggest that HLA-B51 could be derived from HLA-Bw52 by the combination of a genetic exchange with HLA-B8 and a point mutation (Hayashi et al. 1989). HLA-B35 belongs to the HLA-B5 CREG and is serologically related to Bw6, while HLA-B5 (B51 and Bw52) is related to Bw4. HLA-B35 is serologically closer to HLA-B51 than to HLA-Bw52. Therefore, we have cloned a genomic gene of HLA-B35 and determined its structure to study further the evolution of the HLA-B5 family.

Amino Acid Sequence↗

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged↗

Schistosoma mansoni: suppression of carbamoyl phosphate synthetase (ammonia) and ornithine carbamoyltransferase activities in the liver of infected mice.

ICR female mice infected with cercariae of Schistosoma mansoni exhibited a significant decrease in both total and specific activities of carbamoyl-phosphate synthetase (ammonia) (EC 6.3.4.16) and ornithine carbamoyltransferase (EC 2.1.3.3), and also in the serum urea level. Intraperitoneal administration of the S. mansoni egg granulomas or 15,000g X 30 min supernatant fluid of their extract into the uninfected, normal mice also significantly decreased the total and specific activities of both enzymes without any appreciable histopathological influence on their livers. S. mansoni viable eggs caused a significant decrease in the total and specific activities of carbamoyl phosphate synthetase (ammonia) alone as well as active intraperitoneal inflammation when inoculated into the normal mice by the same route. There was no difference in the amount of food intake between the control and these experimental mice. These findings suggest that the granuloma or inflammatory cells induced by schistosome eggs produce some factor(s) which may be responsible for reduction of these enzymatic activities in experimental schistosomiasis mansoni.

Animals↗

Radiation therapy for brain stem tumor with special reference to CT feature and prognosis correlations.

Seventy-nine patients with tumors of the medulla oblongata, pons, and midbrain treated by radiation therapy between 1962 and 1987 were analyzed. According to histology obtained in 28 cases, 61% were high-grade astrocytomas and 39% were low-grade astrocytomas. The 5- and 10-year survival rates of 71 patients who completed radiotherapy were 17 and 15%, respectively. Various potential prognostic factors were analyzed, and patients with a midbrain tumor, with a low-grade tumor, and without cranial nerve paresis were found to have a better prognosis. Computed tomography (CT) was performed both before and after radiotherapy on 42 patients. The volume of the tumor estimated from the CT image was various, but the tumors could be classified into three types according to the pattern of contrast enhancement (CE). Twenty-three tumors showed no CE, 15 showed a diffuse CE, and 4 showed a ring CE. No-CE tumors were generally hypodense on plain scan and were mostly large, whereas diffuse- or ring-CE tumors were relatively small. A complete response (CR) or partial response was obtained with 77% of the no-CE tumors, 64% of the diffuse-CE tumors, and 50% of the ring-CE tumors. The CR rate was higher in the tumors with a smaller volume. The 5-year survival rates for diffuse-CE, no-CE, and ring-CE tumors were 33, 15, and 0%, respectively. The 5-year survival rate was 56% for tumors smaller than 6 cm3, 16% for tumors between 6 and 20 cm3, and 0% for tumors larger than 20 cm3. In conclusion, (a) ring-CE tumors exhibited a poor prognosis; and (b) a diffuse-CE tumor, or a small or middle-sized no-CE tumor is most likely to be controlled by conventional radiation therapy.

Adolescent↗

17-Desoxy estrogen analogues.

A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents. Estrogen-relative binding affinities were determined, in vivo assays for estrogenic and postcoital antifertility activity were conducted in rats, and selected candidate compounds were further tested for estrogenic activity in monkeys. In the rat, the 17-desoxyestratriene derivatives 8a, 8b, and 30 have shown low estrogenic activity while retaining potent antifertility activity. Structural modifications at the outset included a variety of 17-substituents and an omission of the 17-oxygen functionality, which was previously thought to be necessary for potent activity. The 17 beta-ethyl side chain exhibited the greatest antifertility activity with the largest separation ratio to estrogenicity. Nuclear modification of 17-desoxyethylestrane derivatives at positions 7 and 11 further increased the desired separation of activity, with the 11-hydroxy moiety enhancing separation more than other features.

Animals↗

11 beta-nitrate estrane analogues: potent estrogens.

Various estrane derivatives 1 reacted with cerium ammonium nitrate (CAN) selectively and efficiently to provide 9 alpha,11 beta-defunctionalized derivatives 2, which were subsequently deoxygenated at C-9 with triethylsilane/boron trifluoride etherate to the desired target 11 beta-nitratoestranes 3a, 3b, and 5. When examined for estrogenic and postcoital antifertility activity, 11 beta-nitrates 2c, 2d, and 3b most notably displayed more potent oral activity than did ethynylestradiol.

Animals↗

Analysis of xenoantigenicity of HLA class I molecules by a complete series of human-mouse hybrid genes.

To investigate the xenoantigenicity of HLA class I antigens, a complete series of human/mouse chimeric major histocompatibility complex class I genes was constructed by using the human HLA-B7 and mouse H-2Kb genes. All of these hybrid antigens were stably expressed on L cells at high levels. Nine anti-HLA class I monoclonal antibodies, including 5 monomorphic, 3 broad polymorphic, and 2 specific polymorphic ones, were tested by binding to these cell lines. Our data suggest that the alpha 2 domain of HLA-B7 plays an important role in the formation of the antigenic determinants recognized by all of the anti-HLA class I mAbs tested. However, the antigenic determinants of the monomorphic mAbs were complex. In some cases, all of the three extracellular domains were required for expression of the epitope. The location of xenoimmunogenic site of HLA-B7 antigen was also examined by immunizing (B6xC3H)F1 and C3H mice with the parental and hybrid antigens. Our data suggest that the alpha 1 and alpha 2 domains of HLA-B7 must be expressed together for production of antibodies against monomorphic determinants of HLA class I antigens, while the alpha 3 alone can induce xenoantibodies in (B6xC3H)F1 mice but not in C3H mice.

Animals↗

[Anti-tumor promoting activities and inhibitory effects on Epstein-Barr virus activation of Shi-un-kou and its constituents].

The Kampo-prescription, Shi-un-kou, and its constituent crude drugs [Lithospermum erythrorhizon (1), Macrotomia euchroma (2) and Angelica acutiloba (3)] were assayed for their inhibitory effects on Epstein-Barr virus activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). The crude drugs exhibited inhibitory activity singly and in combinations. In particular, the combination of 2 and 3 yielded enhanced inhibition and lower cytotoxicity. The anti-tumor promoter activity suggested by these results was further investigated in an in vivo study, which demonstrated that Shi-un-kou markedly inhibited TPA-induced skin tumor formation in mice.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of CV-3611, a new free radical scavenger, on ischemic heart failure in conscious beagle dogs.

The effects of CV-3611, a new free radical scavenger, on coronary circulation failure and infarct size after ischemia/reperfusion were studied in conscious beagle dogs. The dogs underwent occlusion of the left circumflex coronary artery for 60 min and then were reperfused for 14 days. The dogs were divided into three groups: a control group, a pre-treated group that received CV-3611 or alpha-tocopherol, and a post-treated group that received CV-3611. During occlusion, varying degrees of ventricular arrhythmia were noted; after reperfusion, the arrhythmia tended to become severe. CV-3611 at a daily dose of 10 mg/kg or 30 mg/kg and alpha-tocopherol at a daily dose of 60 mg/kg reduced the incidence of overall post-occlusion arrhythmia. Coronary blood flow in the control group was reduced to 20% of the preocclusion level at 7 days after reperfusion, whereas in the CV-3611 and alpha-tocopherol treated groups, the decreased coronary flow was remarkably suppressed. The infarct size for the CV-3611- and alpha-tocopherol-treated groups, measured at 14 days after reperfusion, was reduced by 70% when compared with the control group. Based on these observations, it is proposed that CV-3611 exerts its beneficial effects on ischemic tissue by protecting against oxygen free radical-mediated damage induced by ischemia/reperfusion.

Animals↗

Nucleotide sequence of the macromomycin apoprotein gene and its expression in Streptomyces macromomyceticus.

A 1.6 kb Sph I-Sac I DNA fragment from Streptomyces macromomyceticus, expected to include the macromomycin (MCM) apoprotein gene, was sequenced. The fragment (1,556 bp) was found to include a putative promoter, an ORF directing pre-apoprotein which should be split into the leader peptide (Met1 to Gly32) and the MCM apoprotein (Ala33 to Ala144), and a putative terminator. The amino acid sequence deduced from the base sequence of the DNA is consistent with the amino acid sequence previously determined by the Edman degradation and other procedures applied to the protein, except base sequence AAC coding for Asn was found rather than Asp111 previously reported. The GC content of the 3rd letters throughout the ORF was 92% in contrast to the sum of the first and the second letters, 62%. There was a low GC content stretch of 20 bp (30% GC) at about 120 bp upstream of the ORF. The Pst I-Sph I 620 bp fragment including the low GC content stretch showed promoter activity when subcloned in a promoter probe vector. About 700 nucleotides long mRNA, which is long enough to span the ORF and the bordering regions, was identified using the Northern blot analysis. A primer extension experiment showed that the transcriptional starting point was A at 89 bp upstream of the ORF. Dot blot analysis of expression of MCM apoprotein gene indicated that the gene was expressed nearly constitutively, while production of holo MCM (the complex consisting of MCM apoprotein and a specific chromophore) depended greatly on culture conditions.

Amino Acid Sequence↗

Elevation of laminin and beta-subunit of prolyl 4-hydroxylase in the sera of human subjects with Schistosomiasis mansoni.

Serum levels of several markers for liver fibrosis were measured utilizing three groups of human subjects related with schistosomiasis mansoni in northeast Brazil; (1) 20 Schistosoma mansoni egg-positives, who have never been administered with anti-schistosomal drugs, (2) 29 egg-negative inhabitants in the endemic area of schistosomiasis, and (3) 23 egg-negative Japanese immigrants in the non-endemic area. None of these sera were positive for antibody to the surface antigen of human hepatitis B (HBs) and circulating HBs antigen. There was no significant difference in the serum levels of N-terminal peptide of procollagen type-III between the egg-positive subjects and either of the egg-negative Brazilian or Japanese immigrants, whereas the mean value of serum laminin significantly increased in the egg-positive subjects. A significantly higher concentration of serum immunoreactive beta-subunit of prolyl 4-hydroxylase (IR beta PH) was also observed in the egg-positive subjects only in comparison with that of the egg-negative Brazilian. Serum laminin and IR beta PH concentrations of the egg-positive subjects did not correlate with the absorbance of enzyme-linked immunosorbent assay (ELISA) which utilized crude antigens isolated from schistosome adults or eggs. No significant difference in these two parameters was observed between two subgroups of the egg-negative Brazilian or Japanese immigrants divided according to the serological data by ELISA. These findings suggest that serum laminin and IR beta PH levels are worth further evaluation for their usefulness as the marker for liver fibrosis in schistosomiasis.

Adolescent↗

[Scintigraphic estimation of dearterialization after transcatheter hepatic arterial embolization therapy].

Radionuclide angiography was performed by bolus injection of 99mTc-phytate in 10 patients with liver neoplasms before and after the transcatheter hepatic arterial embolization therapy. The ratio of the slopes of the upstrokes for the hepatic arterial and abdominal aortic first transit curves constitutes the regional hepatic arterial to aortic blood flow ratio (RHA/A ratio), which represents quantitatively the arterial blood flow of hepatic region of interest as a fraction of aortic blood flow. The degree of embolic dearterialization was estimated by the change of this ratio derives from the same region of interest for each patient before and after the embolization. The values and post-embolic reduction of the ratio correlated well individually with the angiographic features and other patients' data. The arterial blood supply to the tumor could not be reducted using Lipiodol alone as the embolic material in only 1 case. The finding that the splenic arterial to aortic blood flow ratio (S/A ratio), calculated in the same way, was practically unchanged after the hepatic arterial embolization indicates the good reproducibility of these measurements. This noninvasive method may be helpful to evaluate the therapeutic effect of hepatic arterial embolization.

Aged↗

[High-resolution computed tomography for diagnosing pulmonary complications in patients with lung cancer].

The diagnostic value of high-resolution computed tomography has been assessed in 10 lung cancer patients with pulmonary infiltrates. This method was used to evaluate the radiographic appearance of the new pulmonary disease. The expectorated sputum of each patient was examined for a bacteriologic and cytologic diagnosis. In some patients, the flexible bronchofiberscopy that was accompanied by bronchoalveolar lavage was performed so as to establish the etiologic diagnosis. In conclusion, high-resolution computed tomography was found to be useful in diagnosing pulmonary complications in lung cancer patients.

Adult↗