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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 847 records · Page 47Linked to original sources
PubMed1993

A fucose residue can mask the MUC-1 epitopes in normal and cancerous gastric mucosae.

MUSE11, DF3 and SM3 MAbs react with a synthetic peptide of 20 amino-acids: VTSAPDTRPAPGSTAPPAHG. This sequence is a tandem repeat domain of the mucin-type glycoprotein coded by the muc-1 gene. MUSE11 and DF3 MAbs immunoreact strongly with mucus cells of the normal surface gastric epithelium of Le(a+b-) non-secretors, but in spite of the peptidic nature of the recognized epitope, the same tissue of Le(a-b+) secretors reacts only after treatment with alpha-fucosidase. These reactions are inhibited by the PNA lectin, which recognizes the T disaccharide antigen (beta Gal 1-3 alpha GalNAc), suggesting that the peptide epitope may be close to the T-saccharide structure. The SM3 MAb reacted on the surface gastric epithelium of all individuals after a more drastic deglycosylation using 20 mM periodate. Computer modeling of the MUC-1 immunoreactive glycopeptide containing the H type-3 trisaccharide alpha Fuc 1-2 beta Gal 1-3 alpha GalNAc- bound to the threonine of the PDTRP-pentapeptide shows that the peptide epitope might be masked when the fucose is positioned over the arginine. Thus, a single fucose linked to the T structure could mask the MUC-1 epitopes. In gastric adenocarcinomas, MUSE11 and SM3 epitopes are expressed in 75% (25/33) and 9% (3/33) respectively, while, after partial deglycosylation by periodate treatment, they are positive in 100% (33/33) and 70% (23/33) of cases, respectively.

Adolescent↗
PubMed1993

Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers.

The expression of MMP-7 (pump-1) gene was examined in 10 cases of colorectal cancer by utilizing RT-PCR. In 9 out of 10 cases, MMP-7 mRNA was detected in cancerous tissue, whereas none was detected in adjacent normal colon tissue. However, this message was detected in only 1 out of 6 colon-cancer cell lines. In colonic mucosa from 3 patients with ulcerative colitis it was not detected. The expression of MMP-2 (72-kDa type-IV collagenase) mRNA was also investigated in the same tissue samples, and was detected in all samples, including cancerous and non-cancerous tissue. Our data suggest that MMP-7 is expressed in a tumor-associated manner in colorectal cancers and may play a role in tumor progression.

Adult↗
PubMed1993

Randomized study of individualized induction therapy with or without vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 Study of the Japan Adult Leukemia Study Group.

BACKGROUND: It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance-intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). METHODS: A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance-intensification therapy was randomized to 4 or 12 courses given every 6 weeks. RESULTS: Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease-free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance-intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French-American-British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. CONCLUSIONS: Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Acute Disease↗
PubMed1993

Precursor polyprotein for multiple neuropeptides secreted from the suboesophageal ganglion of the silkworm Bombyx mori: characterization of the cDNA encoding the diapause hormone precursor and identification of additional peptides.

Peptidergic neurons, which serve as source of various endocrine neuropeptides, were identified in the suboesophageal ganglion (SG) and brain of insects. In the silkworm Bombyx mori, SG is known to secrete two neuropeptides, diapause hormone (DH) responsible for induction of embryonic diapause and pheromone biosynthesis-activating neuropeptide, which share a pentapeptide amide, Phe-Xaa-Pro-Arg-Leu-NH2 (Xaa = Gly or Ser), at the C terminus. We have isolated cDNA clones for DH from the cDNA library of SG by using oligonucleotide probes. The molecular characterization of the cDNA reveals that the mRNA encodes an open reading frame consisting of 192 aa residues in which the 24-aa DH peptide is localized at the N-terminal region just after the signal peptide. A homology search proposed that the cDNA encodes pheromone biosynthesis-activating neuropeptide and three other neuropeptides [alpha-, beta-, and gamma-SG neuropeptide (SGNP)] in the region following DH, all of which are flanked by possible tryptic cleavage sites and share the Phe-Xaa-Pro-Arg-Leu-Gly sequence at the C terminus. Northern hybridization analysis clearly showed that the gene expression was limited to SG. We chemically synthesized alpha-, beta-, and gamma-SGNP and used them to identify components in extracts of SG and to examine biological functions, alpha- and gamma-SGNP were identified in extracts of SG, and the synthetic beta- and gamma-SGNP expressed weak DH activity. These results indicate that DH, along with four other neuropeptides, is generated from a common precursor polyprotein that is encoded by a single mRNA transcribed in neurosecretory cells of SG.

Amino Acid Sequence↗
PubMed1993

Decreased expression of DCC mRNA in human colorectal cancers.

The mRNA expression levels of DCC gene, which is cloned from the deleted region of chromosome 18q in colorectal cancers and thought to be a tumor-suppressor gene, was evaluated in tissue specimens surgically resected from patients with colorectal cancer by RT-PCR. This method was chosen as the expression level of DCC mRNA is below the detectable level for Northern-blot analysis. Semi-quantitative measurements of DCC mRNA were performed based on a standard curve defined by serial dilution of DCC cDNA. As a result, the expression level of DCC mRNA was found to be lower in 17 out of 30 colorectal cancers than in adjacent non-cancerous tissues. Inclusion of smooth muscle in tissue specimens was observed to have little disturbing effect on comparisons between cancerous and non-cancerous regions. In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.

Actins↗
PubMed1993

Rabbit eye irritation caused by wearing toxic contact lenses and their cytotoxicities: in vivo/in vitro correlation study using standard reference materials.

To clarify the relationship between eye irritancy and cytotoxic potential induced by irritant materials, we made lenses coated with standard reference materials (SRMs) prepared from various amounts of zinc diethyldithiocarbamate (ZDEC) and polyurethane (PU). Zinc diethyldithiocarbamate was classified as a mild irritant by the Draize eye irritation test. When ZDEC-SRM coated contact lenses were applied to rabbit eyes, Draize scores increased in proportion to both the ZDEC and PU concentrations used for coating. Furthermore, correlation with the cytotoxic potential (gamma = -0.93) was better than with lactate dehydrogenase (LDH) activities of tears from rabbit eyes wearing these coated lenses (gamma = 0.78). In conclusion, in vivo eye irritancy induced by wearing lenses could be estimated quantitatively with the cytotoxic potentials using a colony assay. Furthermore, we could compare different sensitivities caused by the same set of SRMs among three different sites of tissue. As a result, the order of sensitivity was eye > muscle >> skin.

3T3 Cells↗
PubMed1993

Primary structure of the variable regions of a monoclonal antibody MUSE11 recognizing the tandem repeat domain of a mucin core protein, MUC1.

A monoclonal antibody (MAb) MUSE11 recognizes an epitope in the tandem repeat domain of a mucin core protein, MUC1. We show that the epitope of MAb MUSE11 could be within the continuous amino acid sequence PDTRPAPG. Since there is increasing evidence indicating that this region is highly immunogenic, cDNA cloning of the variable regions of heavy-chain (VH) and of light-chain (VL) of MAb MUSE11 was performed by using RT-PCR to provide a basis for analyzing the structure of the antibody-antigen complex and for producing anti-idiotypic antibodies. The deduced amino acid sequence revealed that the VH and VK of MAb MUSE11 could be assigned to subgroups IIIA and II of mouse immunoglobulin heavy and light chains, respectively. When compared with the V regions of other MAbs in the same subgroup, the complementary determining region 3 (CDR3) in the VH region of MAb MUSE11 consisted of a unique sequence that may be important in defining the specificity of MAb MUSE11.

Amino Acid Sequence↗
PubMed1993

Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis.

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.

Adenocarcinoma↗
PubMed1993

Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats.

The usefulness of transabdominal ultrasonography in the diagnosis of 3,2'-dimethyl-4-aminobiphenyl- and testosterone propionate-induced tumors of the urogenital organs was evaluated in F344 rats. Seven mass lesions (1 ventral prostate, 1 dorsolateral prostate, 3 seminal vesicles, and 1 kidney) in the urogenital organs could easily be diagnosed concerning size and localization by ultrasound. Histological examination revealed a lesion in the ventral prostate to be an abscess and the other tumors to be malignant. Three hydronephroses by tumor invasion to the ureter, and six tumors in organs other than the urogenital organs could be detected by ultrasound. The threshold of malignant tumor detection by ultrasound was 7 mm in actual length. The size of the mass lesion estimated by ultrasound correlated well with the direct measurement (r = 0.96). Transabdominal ultrasonography is useful for diagnosing the localization of experimental tumors and accurately measuring their size in the urogenital organs of rats.

Adenocarcinoma↗
PubMed1993

Recombinant human IL-5 augments immunoglobulin generation by human B lymphocytes in the presence of IL-2.

The biological activity of interleukin-5 (IL-5) on human B lymphocytes was examined by using a newly purified recombinant human IL-5 preparation. Different densities of B cells from human tonsil samples were isolated by Percoll density gradient from nonrosetted cells. The IL-5 preparation did not act as a B cell growth factor on the large (in vivo-activated) or small (resting) B cells after activation with polyclonal B cell activators. The IL-5 augmented the immunoglobulin (Ig) generation of Staphylococcus aureus Cowan strain I (SAC)-activated B blasts in the presence of interleukin-2 (IL-2). The effect of IL-5 on Ig generation was greater in pokeweed mitogen (PWM)-driven B blasts than that in SAC-induced B blasts when assessed by enzyme-linked immunosorbent assay. The amounts of mu RNA isolated from IL-5/PWM-treated cells were also larger than those from IL-5/IL-2-treated B blasts. These results suggest that the human IL-5 can increase Ig generation of B cells in the presence of IL-2 by working at the level of mRNA coding for Ig.

B-Lymphocytes↗
PubMed1993

Mapping of the Mod-1 locus on mouse chromosome 9.

A new method for typing the Mod-1 locus on mouse Chromosome (Chr) 9 was developed, based on restriction fragment length polymorphism (RFLP) within a polymerase chain reaction (PCR)-amplified fragment. The new method led us to revise the strain distribution pattern (SDP) of Mod-1 in the BXD (C57BL/6J x DBA/2J) and AKXD (AKR/J x DBA/2J) recombinant inbred (RI) strains. The new SDP eliminates several previously reported examples of double recombination events between Mod-1 and the closest flanking loci in the BXD and AKXD strains. In the BXD strains, the revised SDP of Mod-1 was identical to that of the Mod-1-related D9Rtil locus. Thus, the identity of D9Rtil as a Mod-1-related locus rather than Mod-1 itself is in question. The method was also applied to an interspecific backcross panel between an inbred strain of Mus musculus molossinus (MSM/Ms) and C57BL/6J to map Mod-1 with respect to surrounding microsatellite loci, defining the proximal localization of Mod-1 with respect to D9Mit10 with a genetic distance of 0.6 +/- 0.6 cM.

Animals↗
PubMed1993

Effects of body and head positions on bilateral difference in tympanic temperatures.

We have examined the nonparallel changes in tympanic membrane temperatures (Tty) from the two ears in response to various changes in body and head positions. Upon assuming a lateral recumbent position, the Tty on the lower side increased while that on the upper side decreased. Pressure application over a wide area of the lateral chest only caused inconsistent and obscure asymmetric changes in Tty. A lateral flexion of the head with the subject sitting upright and a rotation of the head to the side in a supine position induced an increase in the Tty on the lower side compared to that on the upper side. The temperature and blood flow of the forehead often decreased on the lower side and increased on the upper side, although such responses were not always concomitant with the asymmetric changes in Tty. A dorsal flexion of the head with the subject in a reclining position caused a slight increase in the Tty, whereas raising the head upright induced a slight decrease in them. Two additional experiments were carried out with single photon emission computed tomography using 99mTc-hexamethylpropyleneamine oxime as tracer, and a slight, relative decrease in counts was noted in the right hemisphere during rotation of the head to the right. These results would strongly suggest that unilateral increases and decreases in Tty could have been caused by one-sided decreases and increases, respectively, in blood flow to the brain and/or the tympanic membrane, induced by a vasomotor reflex involving vestibular stimulation.

Adult↗
PubMed1993

A new Pax gene, Pax-9, maps to mouse chromosome 12.

Members of the Pax gene family have recently been shown to play important roles in mouse embryogenesis. Of eight so far characterized Pax genes, three have been associated with mouse developmental mutants. Here we report the cloning of a new Pax gene, Pax-9. Most of the DNA sequence encoding the highly conserved paired domain has been determined and compared with previously known paired domains. This comparison classifies Pax-9 as a member of the same subgroup as Pax-1/undulated. By analysis of the segregation of a Pax-9 restriction fragment length polymorphism and a large number of simple sequence length polymorphisms in an interspecific C57BL/6 x Mus musculus mollosinus backcross, Pax-9 was mapped close to the D12Nds1 locus on the proximal part of Chromosome (Chr) 12.

Amino Acid Sequence↗
PubMed1993

The genetic map around the tail kinks (tk) locus on mouse chromosome 9.

Tail kinks (tk) is a classical mouse skeletal mutation, located on Chromosome (Chr) 9. As the first step for the positional cloning of the tk gene, we have established a genetic map of a region surrounding the tk locus by generating a backcross segregating for tk. From this backcross, 1004 progeny were analyzed for the coat-color phenotype of the proximally located dilute (d) gene and for the distally flanking microsatellite marker, D9Mit12. Fifty-six recombinants between d and tk and 75 recombinants between tk and D9Mit12 were identified, completing a panel of 130 recombinants including one double recombinant. This panel allowed us to map five microsatellite loci as well as d and Mod-1 with respect to tk. We show that one of the microsatellite markers mapped, D9Mit9, does not recombine at all with tk in our backcross. This indicates that the D9Mit9 locus will serve as a good starting point for a chromosomal walk to the tk gene.

Animals↗
PubMed1993

A long term observation of antibody status to chicken anaemia virus in individual chickens of breeder flocks.

The antibody status to chicken anaemia virus (CAV) in four layer breeder flocks was evaluated. Sera were periodically collected from the same 17 to 20 individual chickens of each flock ranging in age from 10 to 63 weeks old. The neutralising and fluorescence antibody were detectable in individual chickens during the observation periods ranging from 13 to 44 weeks. A high prevalence of both neutralising and fluorescence antibodies was observed; however, the prevalence of fluorescence antibody in older chickens was lower than that of neutralising antibody. The geometric mean (GM) of neutralising antibody titres, after all the chickens examined had seroconverted in flocks 1, 2 and 4, ranged from 373.2 to 2940.6. In flock 1, the GM titre at 63 weeks old was significantly lower than that at 37 and 52 weeks old. In flock 4, the GM titre at 48 weeks old was significantly lower than that at 24 and 35 weeks old. In flock 2, the GM titre at more than 31 weeks old significantly increased compared with that at 25 weeks old; this tendency was not seen in the GM of the fluorescence antibody titres. The results indicate that immunity to CAV can last a long time in naturally infected individual chickens.

Animals↗
PubMed1993

Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.

This study aims at clarifying whether the humoral immune response to the tandem repeat domain of MUC1 can be induced or not in vivo. The expression of MUC1 mRNA in the colon was revealed by Northern blot analysis, and cDNA cloning of an extracellular tandemly repeated domain of MUC1 was then performed to prepare the recombinant MUC1 protein. A cDNA clone coding for ten repeat domains was ligated into an expression vector in prokaryotes, resulting in a recombinant protein which could react with the MAb MUSE11 against an adenocarcinoma-associated antigen whose epitope has been shown to be localized in the tandem repeat domain on MUC1. The reactivity of sera from patients with ulcerative colitis with the recombinant protein was evaluated by SDS-PAGE and Western blot analysis to detect the antibodies against this tandem repeat domain. Five out of 19 serum samples tested positive, and these reactions were totally inhibited by MAb MUSE11, suggesting that the epitope recognized by these antibodies in sera is almost identical to that recognized by MAb MUSE11. The data represent the first demonstration of antibody production against a peptide epitope of the tandem repeat domain of MUC1.

Adolescent↗
PubMed1993

The CYP1A1 gene and cancer susceptibility.

A close correlation between cigarette smoking associated lung cancer incidence and an Msp I restriction fragment length polymorphism (RFLP) of the human P-450 1A1 (CYP1A1) gene was found in a Japanese population in terms of genotype frequency and cigarette dose. A Val/Ile codon difference in the primary structure of the CYP1A1 protein (Val-, Ile-type) was in linkage disequilibrium with the Msp I RFLP. A synergistic increase in susceptibility to lung cancer was found when combining genotyping of CYP1A1 and the Mu-class of glutathione S-transferase (GST1). Interindividual variability in the genetic make-up of carcinogen metabolizing enzymes may thus be a key host factor to explain the differences in susceptibility to chemical carcinogenesis among individuals.

Cytochrome P-450 Enzyme System↗