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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 1,153 records · Page 64Linked to original sources

Effect of intravesical instillation of antitumor drugs in the development of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumors in rats.

We examined the effects of intravesical instillation of adriamycin (ADM) and cis-diammine-dichloroplatinum (CDDP) on the development of bladder tumors induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in 115 rats. Intravesical instillation was performed in two ways; continuous administration (5 times a week for 5 weeks) and intermittent administration (once a week). Group 1 (control group) did not receive intravesical instillation. Group 2 I(ADM), group 3 (CDDP) and group 4 (physiological saline) were continuous type. Group 5 (ADM), group 6 (CDDP) and group 7 (physiological saline) received intermittent administration. Bladder weight was significantly higher in group 4 than in groups 1 or 7, and that in groups 2 and 3 than that in group 5 and 6. In groups 2, 3, 5 and 6 bladder weight was almost normal or higher than in the control group, and in group 3 histologically cancer was not seen in one rat. Physiological saline had promoting activity, and ADM and CDDP had both inhibitory and promoting activities. Also, intravesical instillation itself was suggested to promote tumor development under carcinogenic circumstances. We conclude that intermittent intravesical instillation should be performed to inhibit tumor recurrence and intravesical instillation therapy should not be performed clinically for a long period.

Administration, Intravesical↗

[Studies of progressive factors of stage A prostatic cancer].

We studied the progressive factors for incidental carcinoma of the prostate of 38 patients. Effects of anti-androgen drugs for the development of incidental carcinoma were examined. There were no statistical differences with age, tumor size, histopathological grade, or invasion of BPH capsule. However, the tumor progression rate was high for a tumor size of more than 10 mm or poorly differentiated adenocarcinoma. Therefore, tumor progression was related with tumor size and histopathological grade. Of 15 patients with stage A1 disease, two patients had tumor progression. Patients with stage A1 disease are being followed with no treatment, but radical treatment may be necessary for young men. Patients with stage A2 disease must be treated with radical prostatectomy, radiation therapy or hormone therapy case by case. None of the patients who were treated with anti-androgen drugs had stage A1 disease. Patients not treated had stage A1 and A2 diseases. Anti-androgen drugs may have inhibited the development of stage A1 disease.

Adenocarcinoma↗

[Idiopathic retroperitoneal fibrosis: report of 4 cases].

We report 4 cases of idiopathic retroperitoneal fibrosis (IRF). Two cases were demonstrated by surgical biopsy, and in one of them ureterolysis was performed at the same time. After pathological diagnosis, these two patients were treated by steroid therapy. The other two patients were suspected to have acute renal failure due to IRF, and they were treated by nephrostomy or by double-J ureteral stent. In one of them retroperitoneal fibrous tissue had almost disappeared on CT examination. None of these 4 patients have had recurrence of IRF.

Acute Kidney Injury↗

Detection of novel proteins associated with secondary amyloidosis and Alzheimer's disease by monoclonal antibody.

We have established a monoclonal antibody (MoAb) AM34 (IgG1) which was prepared by a hybridoma constructed from fusion between murine myeloma cells and murine splenocytes. Crude amyloid proteins which were used as immunogen, were extracted from the kidney of a patient with rheumatoid arthritis by the distilled water method. This antibody strongly reacted with all 8 cases of secondary amyloidosis, but did not react or very weakly reacted with 17 tissue sections of primary or myeloma-associated amyloidosis. Other amyloid tissues did not give any positive reaction. Interestingly, 6 brain tissues of Alzheimer's disease clearly showed positive staining with this antibody, whereas two apparently normal brain tissues exhibited negative staining. Senile plaque cores, neurofibrillary tangles (weakly stained) and cerebrovascular amyloid in Alzheimer's disease were stained. Absorption of the MoAb AM34 with the crude amyloid proteins abolished the immunoreactivity of the MoAb AM34 not only with the kidney tissue section of the secondary amyloidosis, but also with the above mentioned portions of the brain in the case of Alzheimer's disease. Therefore, these immunohistological data suggest that the MoAb AM34 recognizes common epitope which exists in amyloid deposits of both secondary amyloidosis and Alzheimer's disease. An inhibition test on the kidney section showed that the reactivity of MoAb AM34 was not at all inhibited by the pretreatment of the section with 10 times higher concentration of anti-human amyloid A (AA) MoAb KM268 which was prepared against synthetic peptides of AA protein, suggesting that MoAb AM34 might react with amyloid-related protein other than AA protein. In addition, MoAb KM268 did not react with any lesions in Alzheimer's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

Immunochemical characterization of adenocarcinoma-associated antigen YH206.

The antigen recognized by MAb YH206 is mainly expressed in adenocarcinomas and is also detected in the sera of cancer patients (Hinoda et al., 1987). This antigen (antigen YH206) was chemically characterized and purified by column chromatography. SDS-PAGE analysis revealed a broad component in the high-molecular-weight range which was clearly detectable by carbohydrate (PAS) but not by protein (silver) stain. Agarose gel electrophoresis and immunoblotting of antigen YH206 indicated that it consists of a high-molecular-weight component (more than 2,000 kDa). Treatment of antigen YH206 with alkali suggested that the antigenic determinant consists of carbohydrate chains of mucin type. Density gradient ultracentrifugation revealed that the activity of antigen YH206 is localized at a density of 1.45 g/ml, suggesting that antigen YH206 is a mucin. Neuraminidase treatment of antigen YH206 indicated that the epitope is cryptic and contains an asialocarbohydrate chain. Once antigen YH206 has been purified by affinity chromatography, neither CA19-9 antigen nor DU-PAN-II antigen can be detected, although they were present at very high levels in the crude ascitic starting material; these last two are representative carbohydrate antigens which are widely used for serodiagnosis to detect adenocarcinomas.

Adenocarcinoma↗

Sigma region located between C mu and C delta genes of human immunoglobulin heavy chain: possible involvement of tRNA-like structure in RNA splicing.

Noncoding regions within the cluster of immunoglobulin heavy chain constant genes in the human genome contained a number of repeats. In the mu-delta intron, two repeating units were contained. One 442-base-long fragment located JH-mu intron (defined as "sigma mu(sigma mu)") occupied the position in the mu-delta intron. The other 1166-base-long fragment located somewhere in front of S (class switch) region of C gamma gene was also found in the mu-delta intron. We defined the repeats in the mu-delta intron as "SIGMA (sigma)". The polarities of the longer repeats in the genome were opposite between the mu-delta intron and the upstreams of C gamma genes. These inverted copies (defined as sigma gamma 3 and sigma gamma 4), located 6 kb upstream of their respective C gamma's, were apparently transcribed in vitro, via RNA polymerase III and transcripts should have contained tRNA-like structures. Small DNA fragments capable of encoding tRNA-like structures were also found in corresponding regions of mouse Ig C gamma cluster.

Animals↗

Structure and function of the myoglobin containing octaethylhemin as a prosthetic group.

Spectrophotometric titration of ferric octaethylporphyrin (OEP) with apomyoglobin revealed their 1:1 complex formation. Proton NMR spectrum of the OEP-reconstituted deoxymyoglobin exhibits an exchangeable peak from the proximal F8 histidine at 78.5 ppm, indicating the incorporation of iron OEP into the heme cavity to form the Fe-N(His-F8) bond. OEP metmyoglobin without external ligand has an iron-bound water that deprotonates above pH 7.8. Affinities of the aquometmyoglobin for several ionic ligands were comparable with those of native metmyoglobin. Deoxy OEP myoglobin at 25 degrees C reversibly binds oxygen with an affinity of P50 = 0.8 mm Hg, which is similar to that of native protein. These results indicate that iron OEP serves as a prosthetic group for myoglobin with normal function, despite the significant structural and electronic difference between OEP and protoporphyrin. The unexpected functional similarity between native and OEP myoglobins was interpreted in terms of a structural perturbation at the heme distal site caused by introduction of bulky OEP into the heme pocket.

Animals↗

Improved methods for separating hydrolytic granules of neutrophil leucocytes.

Highly efficient methods for isolating two hydrolytic granules of neutrophils are described. Neutrophil obtained from guinea pig peritoneal exudate cells were washed extensively with isotonic sucrose and then treated with heparin. More than 95 per cent of the cells so treated were disrupted with a Dounce homogenizer. Since nuclei were broken, leaving other organelles intact, homogenates were incubated with DNase to reduce viscosity. Postnuclear supernatants were centrifuged on a discontinuous gradient of Percoll. Azurophil granules, high in beta-glucuronidase activity, sedimented at fractions of d = 1.081 and showed very little activity of other marker enzymes. High neutral alpha-glucosidase activity was observed in granular fractions of d = 1.038 and it is suggested that this is a marker for specific granules of neutrophils.

Animals↗

Binding of heparin onto ethylene-vinyl alcohol copolymer membrane.

Heparin was ionically bound onto the surface of an ethylene-vinyl alcohol copolymer (EVAL) membrane which was derivatized by aminoacetalization to produce cationic surface charges. The amount of bound heparin was proportional to the ion exchange capacity of the aminoacetalized membrane and the maximal amount obtained in this experiment was 96 Unit/cm2 (0.59 mg/cm2). Plasma recalcification times were measured for the heparinized membrane thus obtained. Recalcification times increased proportionally with the amount of heparin bound on the membrane, while original EVAL membranes and the non-heparinized aminoacetalized membrane did not show increases in recalcification times. This means that the heparinized EVAL membrane has a more nonthrombogenic property due to the release of heparin. The apparent amount of heparin released from the membrane into plasma was estimated from plasma recalcification times. The release rate was 0.30-0.33 Unit/cm2/h (1.8 X 10(-3)-2.0 X 10(-3) mg/cm2/h) for the membranes whose surface was considered to be saturated with heparin. The release amount was about 0.6% compared to the adsorbed heparin in the case of the 96 Unit/cm2-heparinized membrane incubated in plasma for 60 min.

Binding Sites↗

Clinical characteristics of prostatic cancer detected by mass screening.

Since 1981 we have been studying prostate cancer (Pca) by mass screening in three cities, eight towns and seven villages in Gunma prefecture, Japan. From 1981 to 1985, 5,770 subjects were examined. The clinical character of Pca detected by mass screening is compared with control (i.e., Pca detected in the outpatient clinic in Gunma University). Of the 54 Pca patients detected by mass screening (Stage B: 28, C: 8, D: 18), approximately 50% had early-stage Pca. The ratio of early-stage Pca is significantly higher than in the control. An extended survival rate in high-stage Pca detected by mass screening also was observed through comparison with control. We determined two types of Pca in advanced stage: (1) asymptomatic or less symptomatic and better prognostic Pca found in mass screening and (2) symptomatic and worse prognostic Pca found in control.

Acid Phosphatase↗

A monoclonal antibody to the carbohydrate chain on human hepatocellular carcinoma-associated antigen which suppressed tumor growth in nude mice.

There have been few reports stating that monoclonal antibody alone inhibits human solid tumor growth in vivo. The present study demonstrated that monoclonal antibody S1 (IgG2a), which recognized the antigenic determinant of the carbohydrate moiety, showed antibody-dependent cell (or macrophage)-mediated cytotoxicity (ADCC or ADMC) in conjunction with murine splenocytes of both BALB/c and athymic mice. In vivo experiments demonstrated that the antibody S1 clearly prolonged the survival of athymic mice which had been inoculated with a human liver carcinoma cell line. In addition, the antibody S1 significantly suppressed the human hepatoma line transplanted s.c. into nude mice. 125I-Labeled monoclonal antibody S1 revealed that the antibody accumulated significantly in the tumor mass. Many mononuclear cells were observed surrounding tumor cells when the antibody was given. This model system might be useful for analyzing the ADCC (or ADMC) mechanism in vivo.

Animals↗

Quantitative assessment of cerebral blood flow using technetium-99m-hexamethyl-propyleneamine oxime: Part I, Design of a mathematical model.

To design a mathematical model for quantifying cerebral blood flow using 99mTc-hexamethyl-propyleneamine oxime (HM-PAO), basic studies were performed in animals and human volunteers. Microautoradiography revealed that HM-PAO crossed the blood-brain barrier. Thin layer chromatographic studies demonstrated the rapid disappearance of free HM-PAO in the brain tissue. Back diffusion from brain to blood was found negligible. From these observations, the familiar microsphere model was employed in the measurements of blood flow with HM-PAO. This, however, resulted in much lower flow values than simultaneously obtained values with the labeled microspheres. This underestimation was ascribed to the high affinity of HM-PAO to blood cells and serum protein. Taking the binding of HM-PAO to blood components into consideration, the following model equation was designed for quantifying cerebral blood flow: Ce(t) = Ca(t)-kCa(t)*exp(-kt), Cb(T) = F integral of T0 Ce(t)dt, where Ce and Ca are the free HM-PAO concentration in the intravascular space and the arterial whole-blood concentration of HM-PAO, respectively, as a function of time (t), Cb is the brain activity concentration, k is the rate constant for the binding of HM-PAO to the blood components, F is the blood flow value, T is time of measurement, and * denotes the operation of convolution. In clinical studies, Ca(t) and Cb(T) are obtainable from a dynamic single photon emission computerized tomographic study of the brain and multiple arterial blood sampling, respectively. The values for F and k can be estimated using a nonlinear least squares fitting method.

Animals↗

Isolation and characterization of horridum toxin with arginine ester hydrolase activity from Heloderma horridum (beaded lizard) venom.

A hemorrhagic toxin with lethal and arginine ester hydrolytic activities was isolated from Heloderma horridum (beaded lizard) venom by Sephadex G-75, DEAE-Sephacel, and Q-Sepharose column chromatography. The hemorrhagic toxin was shown to be homogeneous as demonstrated by a single band on acrylamide gel electrophoresis and immunodiffusion. Its molecular weight is approximately 31,000 with an isoelectric point of 3.9. Hemorrhagic, lethal, and benzoyl-L-arginine ethyl ester hydrolytic activities of this preparation were inhibited by diisopropyl fluorophosphate (DFP), N-bromosuccinimide, and beta-mercaptoethanol, suggesting that serine, tryptophan, and disulfide bonds are involved in these activities. Also there was an increase in creatine kinase activity in mice serum which is an indicator that the toxin is involved in muscle damage. This protein was stable to heat and pH ranges between 2 and 11. The Michaelis constant (Km), for benzoyl-L-arginine ethyl ester, and inhibition constant (Ki), for DFP, were found to be 6.9 X 10(-3) and 1.93 X 10(-4) M, respectively.

Amino Acid Sequence↗

Kallikrein-like enzyme from the venom of Agkistrodon p. piscivorus.

1. A kallikrein-like enzyme was isolated from Agkistrodon p. piscivorus venom by Sephadex G-100, DEAE-Sephacel and S-Sepharose column chromatographies. 2. A kallikrein-like enzyme was shown to be homogeneous as demonstrated by a single band on acrylamide gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunodiffusion. 3. Its molecular weight is approx. 29,000 with an isoelectric point of 7.8. 4. A kallikrein-like enzyme is able to cleave a kininogen analog to release bradykinin, and the B beta chain of fibrinogen. These proteolytic and tosyl-L-arginine methyl ester hydrolytic activities were inhibited by diisopropyl fluorophosphate, suggesting that the serine hydroxyl group is involved in enzymatic activities.

Amino Acids↗

Changes in plasma thyroid hormones, luteinizing hormone (LH), estradiol, progesterone and corticosterone of laying hens during a forced molt.

1. Circulating concentrations of iodothyronines, luteinizing hormone(LH), estradiol(E2), progesterone and corticosterone were measured in hens before, during, and after a forced molt induced by fasting. 2. Corticosterone increased at the onset of molt, peaked at the maximal molt and returned to pre- and post-molt levels. LH, E2 and progesterone declined during the molt, and the decline was coincident with the cessation of egg production. 3. Thyroxine(T4), triiodothyronine (T3) and reverse triiodothyronine(rT3) increased during the molt. The increases of T4 and T3 were not abolished even if the forced molt was conducted in mild weather.

Animals↗