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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 1,099 records · Page 61Linked to original sources
PubMedDate not supplied

Bis(hydroxamamide)-based bifunctional chelating agent for 99mTc labeling of polypeptides.

To develop chelating molecules that provide 99mTc-labeled polypeptides of high in vivo stability and high specific activities under mild reaction conditions, an asymmetrical bis(benzohydroxamamide) compound with an amine group, 4'-aminomethyl-N,N'-trimethylenedibenzohydroxamamide [NH2-C3(BHam)2], was designed and synthesized. The amine residue of NH2-C3(BHam)2 was converted to a maleimide group by reaction with N-succinimidyl-6-maleimidohexanoate, and the conjugation product was coupled to thiol groups of a monoclonal antibody against osteogenic sarcoma (OST7, IgG1) pretreated with 2-iminothiolane to prepare C3(BHam)2-OST7. 99mTc radiolabeling of C3(BHam)2-OST7 was performed by the exchange reaction with [99mTc]glucoheptonate. [99mTc]C3(BHam)2-OST7 was further characterized using directly radioiodinated OST7 ([125I]OST7) and [111In]labeled OST7 with 1-[4-[(5-maleimidopentyl)amidobenzyl]ethylenediamine-N,N, N'N'-tetraacetic acid (EMCS-Bz-EDTA) as references. [99mTc]C3(BHam)2-OST7 was obtained with radiochemical yields of over 94% at protein concentrations as low as 0.2 mg/mL at room temperature for 1 h. [99mTc]C3(BHam)2-OST7 remained stable after incubation in freshly prepared murine plasma and in the presence of cysteine. Similar binding affinities to tumor cells were observed between [99mTc]C3(BHam)2-OST7 and [125I]OST7. When injected into normal mice, [99mTc]C3(BHam)2-OST7 exhibited radioactivity levels in the blood similar to [111In]-EMCS-Bz-EDTA-OST7 up to 24 h postinjection with significantly faster elimination rate of the radioactivity from the liver. In nude mice bearing osteogenic sarcoma, no significant differences were observed in the radioactivity levels in the blood and the tumor between [99mTc]C3(BHam)2-OST7 and [125I]OST7 at 24 h postinjection. These findings indicated that C3(BHam)2 provided 99mTc chelate of high stability at low concentrations even when conjugated to an intact antibody. Such characteristics render bis(hydroxamamide) compounds useful as chelating molecules for preparation of 99mTc-labeled polypeptides.

Amides↗
PubMedDate not supplied

Intracellular metabolic fate of radioactivity after injection of technetium-99m-labeled hydrazino nicotinamide derivatized proteins.

Hydrazino nicotinate (HYNIC) has been shown to produce technetium-99m (99mTc)-labeled proteins and peptides of high stability with high specific activities. However, persistent localization of radioactivity was observed in nontarget tissues such as the liver and kidney after administration of [99mTc]HYNIC-labeled proteins and peptides, which compromises the diagnostic accuracy of the radiopharmaceuticals. Since lysosomes are the principal sites of intracellular catabolism of proteins and peptides, 99mTc-HYNIC-labeled galactosyl-neoglycoalbumin (NGA) was prepared using tricine as a co-ligand to investigate the fate of the radiolabel after lysosomal proteolysis in hepatocytes. When injected into mice, over 90% of the injected radioactivity was accumulated in the liver after 10 min injection. At 24 h postinjection, ca. 40% of the injected radioactivity still remained in liver lysosomes. Size-exclusion HPLC analyses of liver homogenates at 24 h postinjection showed a broad radioactivity peak ranging from molecular masses of 0.5-50 kDa. RP-HPLC analyses of liver homogenates suggested the presence of multiple radiolabeled species. However, most of the radioactivity migrated to lower molecular weight fractions on size-exclusion HPLC after treatment of the liver homogenates with sodium triphenylphosphine-3-monosulfonate (TPPMS). The TPPMS-treated liver homogenates showed a major peak at a retention time similar to that of [[99mTc](HYNIC-lysine)(tricine)(TPPMS)] on RP-HPLC. Similar results were obtained with urine and fecal samples. These findings suggested that the chemical bonding between 99mTc and HYNIC remains stable in the lysosomes and following excretion from the body. The persistent localization of radioactivity in the liver could be attributed to the slow elimination rate of the final radiometabolite, [[99mTc](HYNIC-lysine)(tricine)2], from lysosomes, and subsequent dissociation of one of the tricine co-ligands in the low pH environment of the lysosomes in the absence of excess co-ligands, followed by binding proteins present in the organelles. The findings in this study also suggested that the development of appropriate co-ligands capable of preserving stable bonding with the Tc center is essential to reduce the residence time of radioactivity in nontarget tissues after administration of [99mTc]HYNIC-labeled proteins and peptides.

Albumins↗
PubMedDate not supplied

Retroviral gag and DNA endonuclease coding sequences in IgE-binding factor gene.

Immunoglobulin-binding factors are known to regulate the synthesis of B-cell-derived immunoglobulin heavy-chain isotypes. Cloning and nucleotide sequence determination of complementary DNA encoding rodent IgE-binding factors (IgE-BF) revealed that messenger RNA encodes a glycoprotein of 557 amino acids which is expressed as a precursor of relative molecular mass (Mr) 60,000 (60K) in COS7 monkey cells. We report here that the 3' two-thirds of the IgE-BF coding sequence shows a surprising homology (72%) at the DNA level with coding sequences of the gag and pol (DNA endonuclease) genes of the Syrian hamster intracisternal A particle (IAP H18), an endogenous retrovirus. This marked homology demonstrates that the rodent gene encoding IgE-BF is a hybrid gene which evolved very recently by integrating genes of viral origin, and that the encoded polypeptide comprises three separate domains: an IgE-BF domain and retrovirus-derived gag and DNA endonuclease-like domains. This may represent the first report of a cellular gene containing a virus-derived coding sequence.

Animals↗
PubMedDate not supplied

Respiratory health associated with exposure to automobile exhaust. I. Results of cross-sectional studies in 1979, 1982, and 1983.

Three cross-sectional studies were conducted in an effort to investigate the effect of automobile exhaust on respiratory symptoms. Female adult subjects were selected from residents who lived near roadways that were subjected to very heavy traffic. A standard questionnaire was administered to approximately 5,000 people. Distances of the residences from the roadside were adopted as an index of exposure to automobile exhaust. The estimated odds ratios for chronic cough, chronic phlegm, chronic wheeze, shortness of breath, and chest cold with phlegm, relative to distance from the roadside--adjusted by age, smoking status, years at residence, occupation, and type of home heating-ranged from 0.76 to 2.75. The 95% confidence limits of the odds ratios for chronic cough and chronic phlegm excluded or approached 1.00 in each of the studies. This suggests that exposure to automobile exhaust may be associated with an increased risk of certain respiratory symptoms.

Adult↗
PubMedDate not supplied

Genetic structure of Asian populations of Bombus ignitus (Hymenoptera: Apidae).

The genetic structure of seven mainland and island Asian populations of Bombus ignitus was investigated using nine microsatellite markers and the sequences of part of the mitochondrial cytochrome b (cytb) gene. While microsatellite markers showed high genetic variability, no sequence variation was found in the cytb gene fragment analyzed. The number of microsatellite alleles ranged from 9 to 24. Gene diversities per locus per population ranged from 0.378 to 0.992. Analysis of molecular variance (AMOVA) and most pairwise F(ST) values showed significant genetic differentiation between mainland and island populations. Cytb sequences data and microsatellite bottleneck tests indicated that almost all populations were subjected to recent bottlenecks. Our results suggest that B. ignitus populations diverged due to recent bottlenecks and geographic isolation.

Animals↗
PubMedDate not supplied

Inflammation as the possible cause of cystic radiolucencies in carpal bones of patients on hemodialysis.

In this investigation of the etiology of amyloid-associated arthropathy in hemodialysis (HD) patients, determination of whether amyloid deposition triggered the formation of the cystic radiolucent bone lesions was attempted. The relationship between these lesions in carpal bones and carpal tunnel syndrome (CTS) was studied by radiography and tomography, and one of the carpal bones, the os capitatum, was examined histologically at autopsy. The mean number of cystic radiolucent lesions in carpal bones of the 21 patients with CTS was significantly greater than that in the 43 patients without CTS. On tomograms, cystic radiolucent lesions of carpal bones had interconnections with joint spaces. Inflammatory fibrous granulation tissue, with or without amyloid deposits, was found in the cystic lesions. It was concluded that cystic radiolucent lesions in carpal bones of patients on HD was related to CTS, and that synovitis and subsequent chronic inflammation were responsible. Thus, amyloid deposits did not trigger the formation of such lesions.

Amyloidosis↗
PubMedDate not supplied

Computed tomographic findings of Bellini duct carcinoma of the kidney.

OBJECTIVE: To analyze CT findings of Bellini duct carcinoma, a rare variant of renal cell carcinoma. MATERIALS AND METHODS: The CT findings of five cases of Bellini duct carcinoma were reviewed and the findings were recorded. RESULTS: In all cases the affected kidneys maintained the normal outer contours. In four cases the renal masses protruded into the central sinuses. Contrast enhancement was minimal in four cases. CONCLUSION: Bellini duct carcinoma should be suspected in cases with these CT findings.

Adult↗
PubMedDate not supplied

Sequential alteration of proto-oncogene expression in liver, spleen, kidney and brain of mice subjected to whole body irradiation.

Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the sequential alteration of proto-oncogene mRNA expression in liver, spleen, kidney and brain of mice after whole body irradiation (WBI). The mRNAs investigated in this study were Fas, c-fos, c-myc. bcl-2, and p53, and glyceraldehyde-3-phosphate dehydrogenase mRNA was employed as internal control. C3H/He mice aged 9-10 weeks were exposed to WBI of 7 Gy using a cobalt-60 teletherapy unit, without anesthesia, and sacrificed before and 0.1, 0.5, 1, 2, 3, 6, 12, 24, 48 and 96 h after irradiation. Their liver, spleen, kidney and brain were taken and immediately stored in liquid nitrogen until ready for RT-PCR. Each specimen was homogenized to extract RNA for conventional RT-PCR. The liver of mice administered 7 Gy of WBI revealed no significant changes in the expression of each of the mRNAs examined. In the spleen, c-fos mRNA expression decreased at 2 h following irradiation, and increased remarkably thereafter. In the kidney, no significant change in the expression of each mRNA was shown. In the brain c-fos mRNA expression decreased 1-24 h after irradiation, and showed a recovery thereafter. The remarkable differences in the sequential changes of c-fos mRNA expression following irradiation between each organ revealed by the present experiment may be an important aid in determining the tissue-specific radiosensitivity to ionizing radiation. Further investigations are, however, needed to clarify the signal transduction mechanisms which are mediated by the expression of these proto-oncogenes in each tissue following irradiation.

Animals↗
PubMedDate not supplied

Hepatocellular carcinoma developed in a patient with chronic hepatitis C after the disappearance of hepatitis C virus due to interferon therapy.

A 62 year-old man was admitted to Asahikawa Medical College Hospital. Injection therapy of natural interferon-alpha was performed against chronic active hepatitis with hepatitis C virus infection. He successfully responded to interferon therapy with normalization of serum transaminases and disappearance of serum hepatitis C virus RNA. The liver function test remained within normal limits and serum hepatitis C virus RNA was not detected throughout the observation period. Three years later, CT examination demonstrated 2 small hepatic masses. Ultrasound-guided biopsy of the hepatic mass demonstrated well-differentiated hepatocellular carcinoma histologically. Laparoscopic examination revealed chronic hepatitis, but neither active inflammation nor cirrhotic changes were noted as an underlying liver disease. In the liver specimen, hepatitis C virus RNA was not detected by RT-PCR. Percutaneous ultrasound-guided ethanol injection therapy achieved complete necrosis of the hepatocellular carcinoma and there was no recurrence of hepatic cancer during the follow-up period. This case suggests that patients with chronic hepatitis C infection, who have complete disappearance of serum hepatitis C virus RNA by interferon therapy, should be followed-up carefully for the potential development of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Primary squamous cell carcinoma of the stomach: a case report with a review of Japanese and Western literature.

A case of a 75 year-old male with primary squamous cell carcinoma of the stomach is reported. It is extremely rare to see squamous cell carcinoma developing in the stomach, without being accompanied by a component of adenocarcinoma. Up to the present, 18 Japanese and 62 Western cases of this type of carcinoma have been reported in the literature. The origin of this malignancy has not been well elucidated yet and thus, several plausible hypotheses have been proposed. In this presented case, the tumor consisted of only squamous cell carcinoma and the focus of squamous metaplasia was not found histologically in the adjacent mucosa. Therefore, it may be considered that the carcinoma arises from misplaced squamous cell nests of the stomach.

Aged↗
PubMedDate not supplied

MDV glycoprotein D is expressed in the feather follicle epithelium of infected chickens.

Glycoprotein D (gD) and its homologues are essential for many alphaherpesvirus life cycles. A gene encoding a homologue of gD was recently found in the Marek's disease virus (MDV) genome. Interestingly, gD-negative MDV mutants apparently replicate unimpaired in both cell culture and chickens. In this study, we show the expression of the gD homologue of MDV in feather follicle epithelium in infected birds. The gD homologue was detected in a few feather follicles even when most of the follicles were expressing pp38 or gB, other MDV-specific proteins. These observations indicate that the MDV gD homologue is expressed in a very limited set of cells and may be differently regulated. Since feather follicle epithelium of infected birds are the only place where the infectious cell-free MDV virions can be recovered, analysis of the transcriptional regulation of gD may lead to the understanding of the cell-associated nature of MDV.

Animals↗
PubMedDate not supplied

Thyroid metastasis from hepatocellular carcinoma as an initial presentation: a case report.

Although metastases to the thyroid are not uncommon at autopsy, most of these lesions are clinically occult. To our knowledge, this is the first report of a case of hepatocellular carcinoma initially presenting as a thyroid mass. Various radiological studies suggested malignant thyroid tumor, and core needle biopsy was performed. Metastasis from hepatocellular carcinoma was histopathologically suspected, and subsequent abdominal CT revealed advanced hepatocellular carcinoma.

Aged↗
PubMedDate not supplied

Experimental infection of specific-pathogen-free chickens with serotype-1 fowl adenovirus isolated from a broiler chicken with gizzard erosions.

Gizzard lesions were formed in specific-pathogen-free (SPF) white leghorn chickens inoculated with fowl adenovirus (FAV). The virus, serotype 1 FAV 99ZH strain (FAV-99ZH), was originally isolated from the gizzard mucosa of commercial broiler chickens exhibiting gizzard erosion with intranuclear inclusion bodies. Five-day-old and 53-day-old SPF white leghorn chickens were inoculated with FAV-99ZH by both oral and ocular routes and then examined at necropsy on days 3, 5, 7, 10, 14, and 21 postinoculation (PI). There were no clinical signs in any of the chickens after the inoculation. Focal gizzard lesions occurred macroscopically, however, in inoculated chickens at several experimental periods. FAV was recovered from tissue samples of the proventriculus, gizzard, pancreas, and rectum by day 10 or 7 PI but was not recovered from liver samples of any of the chickens. These results indicate that FAV isolated from gizzard erosion is able to reproduce gizzard lesions as necrosis and erosion in SPF white leghorn chickens and that it may have a greater degree of tissue tropism in gizzards and other digestive organs than in the liver.

Adenoviridae Infections↗
PubMedDate not supplied

Epizootic outbreaks of gizzard erosion associated with adenovirus infection in chickens.

Two outbreaks of gizzard erosion in slaughtered broiler chickens in Japan were examined pathologically and microbiologically. The prevalences of such lesions were 9%-11% and 4%-50% in the affected flocks. Affected chickens had no clinical signs. Group I fowl adenovirus (FAV) serotype 1 was isolated from gizzard lesions. Histologically, gizzard mucosa were necrotic. Intranuclear inclusion bodies were seen in the enlarged nuclei of degenerating epithelial cells of the gizzard. The keratinoid layer in the erosion was edematous and desquamated and contained degenerative cells. Moderate to marked inflammatory cell infiltration was observed in the lamina propria and perivascular connective tissue in the submucosa and muscle layer. Immunohistochemical staining showed evidence of FAV antigens in the intranuclear inclusion bodies within degenerating epithelial cells. Ultrastructurally, numerous viral particles were demonstrated in the inclusions.

Adenoviridae Infections↗
PubMedDate not supplied

Pathogenicity of serotype 1 fowl adenovirus in commercial broiler chickens.

The pathogenicity of a serotype 1 fowl adenovirus (FAV-99ZH), isolated from broiler chickens exhibiting gizzard erosion, was investigated in commercial broiler chickens. Five-, 3-, and 1-wk-old commercial broiler chickens were inoculated with FAV-99ZH by both oral and ocular routes. In the 5-wk-old chickens (trial 1), none of which had the maternal antibody to FAV-99ZH, severe gizzard erosions were observed on days 5, 7, and 10 postinoculation (PI). Among the 3-wk-old chickens (trial 2), which were separated into a control group and three treatment groups according to their maternal antibody titer levels, some chickens showed clinical signs such as depression and anorexia. Compared with the control group, all the treatment groups showed decreased weight gain. One treatment group, moreover, showed significantly decreased (P < 0.05) weight gain on day 10 PI. Severe gizzard lesions, such as erosion or ulcers, were observed from day 4 PI in all treatment groups regardless of their maternal antibody levels. The 1-wk-old chickens (trial 3) were separated into a control group and two treatment groups according to their titer levels of the inoculated virus. In spite of high maternal antibody levels, severe gizzard lesions were observed in both treatment groups, which also showed decreased weight gain. One treatment group, inoculated with the higher dose, showed significantly decreased (P < 0.05) weight gain on days 10 and 14 PI compared with the control group. Fowl adenovirus was recovered mainly from gizzard and rectal (including feces) samples from inoculated chickens but was not recovered from liver samples in any of the trials or in any of the control chickens. Although the reproduced disease was similar to that described in a previous report of experimental infection of specific-pathogen-free (SPF) white leghorn chickens with fowl adenovirus, the pathogenicity of FAV-99ZH in commercial broiler chickens was more severe than that in the SPF white leghorn chickens. The results of the present study indicate that FAV-99ZH isolated from gizzard erosion had pathogenicity and produced severe lesions in the gizzards of broiler chickens and that FAV-99ZH could infect and produce illness in broiler chickens with maternal antibodies against this virus.

Adenoviridae Infections↗
PubMedDate not supplied

Outbreaks of adenoviral gizzard erosion in slaughtered broiler chickens in Japan.

Gizzard erosion in broiler chickens was investigated at 18 slaughterhouses in Japan. The condition was observed in 13 of them, and adenoviral gizzard erosion (AGE) was diagnosed histologically, immunohistochemically and virologically in the eroded gizzards from nine of these 13. The antigen-positive intranuclear inclusion body of group 1 fowl adenovirus was observed in the epithelial cells of the affected gizzards, and fowl adenoviruses were isolated from the lesions. In two of the slaughterhouses the total weights of the gizzards disposed of in three years were 3590 kg (0.40 per cent of the gizzards inspected) and 2880 kg (0.19 per cent). Sixteen of the 19 outbreaks of gizzard erosion on 15 farms that were confirmed in three of the slaughterhouses, including the previous two slaughterhouses, were diagnosed as AGE, and the condition was suspected in the other three outbreaks. Most of the adenoviruses isolated were identified as serotype-1 by PCR-restriction fragment length polymorphism. No apparent clinical signs were observed in any of the affected flocks.

Abattoirs↗
PubMedDate not supplied

Pharmacological studies of lappaconitine: supraspinal-spinal interaction in antinociception.

Changes in lappaconitine levels in blood, brain and spinal cord following subcutaneous (s.c.) injection were correlated with the analgesic activity at intervals up to 90 minutes after injection. In the mouse, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections of amounts corresponding to ED50 values in the tail pinch method (i.c.v.: 2333 ng/mouse; i.t.: 1127 ng/mouse) gave peak lappaconitine levels of 1300 ng/g brain and 761 ng/g spinal cord, respectively. However, injection of lappaconitine at ED50 by the s.c. route (7 mg/kg) gave lower peak lappaconitine levels of 320 ng/g brain and 214 ng/g spinal cord. The responses to i.c.v., i.t. and combined i.c.v. plus i.t. administration of lappaconitine were evaluated by the determination of ED50 values, which were plotted as an isobologram. The experimental point is not significantly different from the theoretical additive ED50 point. When a dose equal to the experimental additive ED50 value (i.c.v., i.t. = 620, 413 ng/mouse) was injected, peak lappaconitine levels reached 344 ng/g brain and 241 ng/g spinal cord. Thus, the equianalgesic doses of lappaconitine (ED50 by the s.c. route and additive ED50 by the i.c.v. plus i.t. route) gave closely similar concentrations of the drug in brain and spinal cord. These results indicate that a simultaneous action of lappaconitine on supraspinal and spinal sites is likely to be important for the analgesia produced by systemically administered lappaconitine.

Aconitine↗