Search PubMed⌕ Search

Biomedical subjects

T Kudo

Publications and source records attributed to T Kudo.

At least 253 records · Page 14Linked to original sources

Induction of major histocompatibility complex class II antigens on human colonic epithelium by interferon-gamma, tumor necrosis factor-alpha, and interleukin-2.

Class II antigens are strongly expressed on the inflamed colonic epithelium in inflammatory bowel disease. However, the mechanism of this epithelial class II antigen induction is not fully understood. Increased activities of interferon (IFN)gamma, tumor necrosis factor (TNF)alpha, and interleukin (IL)2 have been shown in the inflamed mucosa of inflammatory bowel disease. Therefore, we studied whether these cytokines could induce class II antigens on the human colonic epithelium. By an organ culture technique, 284 normal colonic biopsy specimens obtained from 49 individuals were cultured in media containing different concentrations of cytokines with/without anti-IFNgamma R antibody. Colonic epithelial class II antigens were identified by the indirect immunoperoxidase staining method with anti-human leukocyte antigen (HLA)-DR, DP, and DQ monoclonal antibodies. IFNgamma, TNFalpha, and IL2 induced epithelial class II antigens in 16 of 16 cases (100%), 2 of 16 cases (12.5%), and 6 of 17 cases (35%), respectively. Epithelial class II antigen expression in response to TNFalpha was induced via IFNgamma but not via IL2. This is the first demonstration that: (i) the induction of class II antigens on the colonic epithelium in response to TNFalpha is mediated via IFNgamma, and (ii) that IL2 induces class II antigens.

Epithelial Cells↗

[Pharmacokinetics of propofol and ketamine during and after total intravenous anesthesia with propofol, fentanyl and ketamine for pediatric patients].

Pharmacokinetics of propofol and ketamine during propofol-fentanyl-ketamine (PFK) anesthesia for pediatric surgery was studied. Plasma levels of propofol (Pp) were maintained approximately at 2.5 micrograms.ml-1 during surgery. Fifteen minutes after the cessation of propofol infusion, Pp decreased to 1.5 micrograms.ml-1. Plasma levels of ketamine (Pk) were maintained at 150-200 ng.ml-1 during the surgery. After the cessation of ketamine infusion, Pk decreased as quickly as Pp. Pk values at 15 minutes and 120 minutes after the cessation of the infusion were 93 ng.ml-1, 24 ng.ml-1, respectively. On the other hand, plasma norketamine (Pn) levels increased gradually during surgery and stayed at 100-150 ng.ml-1 after the end of ketamine infusion to play an important role in post-operative sedation and pain relief. In conclusion, pharmacokinetics of propofol and ketamine in pediatric patients was similar to that in adult patients. PFK anesthesia can be used safely for pediatric as well as for adult patients.

Anesthesia, Intravenous↗

[Clinical indication of propofol for pediatric patients--pharmacokinetics of propofol and ketamine during and after total intravenous anesthesia with propofol, fentanyl and ketamine (PFK) in a neonate].

A 60-day-old neonate boy received hepatic portojejunostomy for biliary atresia under PFK. Pharmacokinetics of propofol and ketamine during and after PFK was also studied. Plasma levels of propofol (Cp) and ketamine (Ck) were maintained at 2 to 3 micrograms ml-1 and at 200 to 300 ng ml-1 during surgery, respectively. Both Cp and Ck decreased quickly after the end of infusions. From the pharmacokinetic point of view, PFK may be safely applied even for neonates.

Anesthesia, Intravenous↗

Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes.

Patients without any evidence of lymph node metastases are supposed to have a fair prognosis, but some of these patients develop recurrent disease unexpectedly after surgery. The object of this study is to examine whether the detection of human papilloma virus (HPV) DNA could be used as a diagnostic marker to predict such recurrences. Two hundred and thirty-six patients undergoing radical hysterectomy and pelvic lymphadenectomy for stage Ib and II cervical cancer at Okayama University Hospital (Japan) from 1988-1994 were reviewed, and only those cases positive for HPV-16 or HPV-18 in primary sites were included in this survey. The E6-E7 region of the HPV genome was amplified by a sensitive nested PCR from archival pelvic lymph node specimens. HPV sequences identical to those of the primary sites were detected in histologically confirmed negative lymph nodes, regardless of histological type or HPV type of the primary lesion, in 9 of 10 patients who recurred within 4 years of surgery. In contrast, histologically confirmed negative lymph nodes from 12 patients with stage IIb disease without evidence of recurrent disease were all negative for the presence of HPV, except for 1 lymph node. The presence of HPV DNA in histologically negative nodes implies the possibility of early nodal involvement or coexistence of undetectable hematogenic dissemination and could therefore be used as a diagnostic marker to predict the unexpected recurrence of these patients.

Adult↗

[Preoperative chemotherapy for advanced colorectal carcinomas--comparison of histological effect between UFT + leucovorin tablet and UFT alone].

The authors analyzed the histological effect of preoperative chemotherapy for 41 colorectal advanced cancer patients using resected specimens. Twenty patients in the UFT + LV group received 400 mg/day of UFT and 30 mg/day of leucovorin for 10-14 days just before the operations. Twenty-one patients with UFT alone received UFT 400 mg/day during the same period. Only one patient in the UFT + LV group developed the side effect of mild leukocytopenia. The histological effect of the UFT + LV group was superior to that of the UFT alone group (p = 0.03). The number of Grade 1a and 1b in the UFT + LV group was 14 (60.9%) and 7 (30.4%), while in the UFT group 16 (66.7%) and 2 (8.3%). Histological examination revealed no lesions which showed Grade 2 and 3 in both groups. There was the tendency for the histological effect in moderately differentiated adenocarcinomas to be superior to that in well-differentiated adenocarcinomas in both group. The histological effect in metastatic lymph nodes was superior to that in the original colorectal lesions in both groups. This suggests preoperative chemotherapy with UFT + LV and UFT could achieve the clinical down-staging of advanced colorectal cancer.

Administration, Oral↗

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗

Up-regulation of a set of glycosyltransferase genes in human colorectal cancer.

The carbohydrate structures of glycoconjugates of cancer cells change markedly in comparison with those of noncancerous cells. We aimed to determine which glycosyltransferases are up-regulated or down-regulated in human colon cancer tissues in order for the dramatic change in carbohydrate structures to occur. The transcript levels of 12 glycosyltransferase genes were measured by a competitive reverse-transcription-PCR method in noncancerous and cancerous colorectal tissues. Eight well- to moderately differentiated and three poorly differentiated carcinomas were examined in comparison with noncancerous colon epithelial tissues adjacent to the carcinoma tissues. Two of the twelve glycosyltransferase genes, Fuc-TIV and ST3Gal II, were significantly up-regulated in all cancerous tissues regardless of the histologic features. Four genes, ST3Gal I, ST6Gal I, beta1,4GalT, and Core2 GnT, showed a tendency toward up-regulation, and a ST3Gal III gene showed a tendency toward down-regulation. The other genes, Fuc-TIII, Fuc-TVI, and ST3Gal IV, which were most abundantly expressed in colorectal tissues, did not show significant up-regulation except in the poorly differentiated carcinomas. The Fuc-TVII gene was expressed at a very low level and was not up-regulated, and the Fuc-TV gene was not expressed at all in the colorectal tissues. Interestingly, all of the 12 glycosyltransferase genes examined, except the Fuc-TV, Fuc-TVI, Fuc-TVII, and ST3Gal III genes, were markedly up-regulated in all of the poorly differentiated carcinomas. We concluded that multiple glycosyltransferase genes are up-regulated, probably leading to extensive glycosylation of glycoconjugates in colorectal cancer cells. Lastly, sialyl Lewis antigens, ie, sialyl Lewis x and a antigens, which are terminal epitopes of sugar chains and well known as tumor-associated antigens, were quantified by Western blotting analysis. Based on the levels of transcripts of the 12 enzymes together with the amounts of sialyl Lewis antigens, we concluded that Fuc-TIII, Fuc-TVI, and ST3Gal IV are mainly responsible for synthesis of the sialyl Lewis antigens in colon tissues, but are not responsible for the augmented expression of the antigens in colorectal cancers. The amounts of sialyl Lewis x and a epitopes on mucins in colon cancer tissues can thus be determined through combinatorial up-regulation of the multiple glycosyltransferase genes.

Adult↗

[Identification of macrophage migration inhibitory factor (MIF) in rat gastrointestinal tract and its role in rat stomach].

Macrophage migration inhibitory factor (MIF) is the first discovered lymphokine. It was originally identified by its ability to prevent the migration of macrophages out of capillary tubes. Since then, the expression of MIF activities has been found at a variety of inflammatory loci, suggesting its role in regulating the function of macrophages in host defence. More recent reports showed that MIF may have functions besides in the immune system. For instance, MIF mRNA and protein are expressed in anterior pituitary cells, brain, embryonic eye lens and differentiating epidermal cells, suggesting its pivotal role in the regulation of neuroendocrine system, cell growth and differentiation. The aim of this study was to examine the presence and localization of MIF mRNA and its product in the gastrointestinal tract of adult rats. For studying the expression of MIF mRNA and protein, Northern blot analysis and immunoblotting were carried out. For examination of cellular localization of MIF in detail, immunohistochemical studies were performed with the use of rabbit polyclonal antibody directed against recombinant rat MIF. MIF mRNA and protein were strongly expressed in the rat gastric mucosa and to a lesser extent in the esophagus, small intestine and colon by Northern blot analysis and immunoblotting. By immunohistochemical study, positive MIF staining was confined within the cytoplasm of parietal cells. Chief cells and surface mucous cells were negative for MIF staining. Intraperitoneal injection of rat gastrin I caused a decline of MIF mRNA level. And after 6 hours of injection, the level of MIF mRNA returned to the level before injection. In the present study, we demonstrate for the first time that MIF mRNA and protein are strongly expressed in gastric parietal cells. Its constitutive expression in parietal cells suggests that MIF may play an important role in parietal cell physiology.

Animals↗

Ten minute 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

We investigated the utility of a 10-min 13C-urea breath test (13C-UBT) using 100mg of 13C-urea; this is a simple and rapid method for the detection of Helicobacter pylori infection. One hundred and fifty-one patients in whom the identification of H. pylori was established by rapid urease test, culture, and histology of six biopsy specimens underwent 254 13C-UBT examinations before and/or after eradication treatment. In the 133 patients who did not receive eradication treatment, the calculated sensitivity of the 10-min 13C-UBT was 99.4% and specificity 100% when the cut-off point was set at 3.5/1000, using a mass spectrometer. In the 121 patients who received eradication treatment, this cut-off point gave a sensitivity of 86.7%, a specificity of 99.1%, and a positive predictive value of 92.9%, with a negative predictive value of 98.1%. There were no significant differences between the diagnosis of H. pylori infection at 1 month and more than 3 months after the endpoint of eradication treatment. The 10-min 13C-UBT is suitable for the diagnosis of H. pylori infection before and after eradication treatment.

Breath Tests↗

[Effect of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery].

Effect of propofol as an agent for anesthetic induction on plasma levels of cortisol, beta-endorphin-like immunoreactivity (beta-ELI), growth hormone (GH) and prolactin were evaluated in 20 non-abdominal surgical patients ranged in ages from 19 to 64 years. Anesthesia was induced with either intravenous propofol 2-2.5 mg in ten patients or intravenous thiopental 4-5 mg in the remaining 10 patients as the control group, and succinylcholine was administered intravenously to facilitate tracheal intubation. Enflurane-nitrous oxide-oxygen was then given to maintain anesthesia in all the patients of both groups. Plasma cortisol levels decreased slightly with anesthesia in the propofol group, but they increased slightly after anesthetic induction in the control group. Therefore they were significantly lower in the propofol group than those in the control group. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma beta-ELI levels were unchanged with anesthesia alone in the patients of both groups. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma GH levels were not affected with anesthesia, but they increased slightly during surgery in both groups. Plasma prolactin levels increased significantly during anesthesia and surgery in both groups, and they decreased after the emergence from anesthesia but were still significantly higher than the preanesthetic values in both groups. The authors' findings suggest that effects of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery are comparable to those of thiopental, and that propofol does not exert inhibitory effect on pituitary-adrenocortical function during anesthesia and surgery.

Adult↗

Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas.

The aim of this study is to address the role of mdm-2-gene amplification in the tumorigenesis of uterine sarcomas. Differential PCR with DNA from formalin-fixed paraffin-embedded specimens was employed in 12 patients with uterine sarcomas. We detected mdm-2-gene amplification in 4 out of 12 uterine sarcomas. The estimated copy number of the mdm-2 gene ranged from 4 to 13. Positive cases included 1 leiomyosarcoma and 3 carcinosarcomas, however, there was no correlation between mdm-2-gene amplification and clinicopathological characteristics. Over-expression of p53 protein was also immunohistochemically studied in the same series of patients: 4 out of 8 carcinosarcomas displayed p53 immunoreactivity. Taking these results together, only one carcinosarcoma was found to have both mdm-2-gene amplification and p53 over-expression. In contrast, half of the patients were found to have alterations either of mdm-2 or of p53. These findings support the notion that mdm-2-gene amplification might be an alternative mechanism for escaping from the regulatory pathway of p53 to suppress cell growth.

Adult↗

Molecular cloning of chicken FTZ-F1-related orphan receptors.

FTZ-F1 is a member of the orphan nuclear receptors, which belongs to the steroid hormone receptor superfamily, and plays a role in the blastoderm and nervous system development in Drosophila. Recently, several FTZ-F1 family genes have been cloned in several species. SF-1/Ad4BPs have been identified as master regulators controlling steroidogenic P-450 genes in mammals and are considered to be the mammalian homologues of FTZ-F1. Moreover, SF-1/Ad4BP plays a critical role in the sexual differentiation of gonads in mammals. In vertebrates, except for mammals, the functional homologue of SF-1/Ad4BP has not been identified before. Herein, we cloned two chicken cDNAs (OR2.0 and OR2.1), which encode putative FTZ-F1 family receptors, by reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). OR2.1 consists of 3255 bp, is expressed in the adrenal glands and gonads, and is considered to be the chicken counterpart of mammalian SF-1/Ad4BP. However, OR2.0 consists of 2945 bp, is expressed in the livers and the adrenal glands, and is considered to be the chicken counterpart of mouse LRH-1, which is a member of the FTZ-F1 family in mammals.

Amino Acid Sequence↗

Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme.

The H genes, encoding an alpha1,2fucosyltransferase, which defines blood groups with the H structure, of four Bombay and 13 para-Bombay Japanese individuals were analyzed for mutations. Four Bombay individuals were homologous for the same null H allele, which is inactivated by a single nonsense mutation at position 695 from G to A (G695A), resulting in termination of H gene translation. The allele inactivated by the G695A was designated h1. The other 13 para-Bombay individuals possessed a trace amount of H antigens on erythrocytes regardless of their secretor status. Sequence analysis of their H genes showed four additional inactivated H gene alleles, h2, h3, h4, and h5. The h2 allele possesed a single base deletion at position 990 G (990-del). The h3 and h4 alleles possessed a single missense mutation, T721C, which changes Tyr 241 to His, and G442T, which changes Asp148 to Tyr, respectively. The h5 allele possessed two missense mutations, T460C (Tyr154to His) and G1042A (Glu348to Lys). The h2, h3, h4, and h5 enzymes directed by these alleles were not fully inactivated by the deletion and the missense mutations expressing some residual enzyme activity resulting in synthesis of H antigen on erythrocytes. Thirteen para-Bombay individuals whose erythrocytes retained a trace amount of H antigen were determined to be heterozygous or homozygous for at least one of h2, h3, h4, or h5 alleles. This clarified that the levels (null to trace amount) of H antigen expression on erythrocytes of Bombay and para-Bombay individuals are determined solely by H enzyme activity. These mutations found in the Japanese H alleles differ from a nonsense mutation found in the Indonesian population. To determine the roles of the H, Se, and Le genes in the expression of H antigen in secretions and Lewis blood group antigen on erythrocytes, the Lewis and secretor genes were also examined in these Bombay and para-Bombay individuals. The Lewis blood group phenotype, Le(alpha- b+), was determined by the combinatorial activity of two fucosyltransferases, the Lewis enzyme and the secretor enzyme, and the secretor status was solely determined by the secretor enzyme activity, not by H enzyme activity. Bombay individuals were confirmed to be homozygous for the inactivated H and Se genes. As expected from the very low frequency of Bombay and para-Bombay individuals in the population, ie, approximately one in two or 300,000, the H gene mutations were found to be very variable, unlike the cases of the point mutations in the other glycosyltransferase genes; the ABO genes, the Lewis gene, and the secretor gene.

Adenine↗

Application of the variable region in 16S rDNA to create an index for rapid species identification in the genus Streptomyces.

Partial nucleotide sequences (120 bp) of the 16S rRNA gene (rDNA) containing a variable alpha region were compared in 89 strains of the genus Streptomyces belonging to eight major clusters of category I in Bergey's Manual of Systematic Bacteriology. Fifty-seven kinds of partial 16S rDNA sequences were observed among the 89 strains. Forty-three of the strains were grouped into 11 'identity groups', based on the fact that the strains in each group shared an identical sequence in the 120-bp region. The results of a phylogenetic analysis based on the 16S rDNA 120-bp sequences revealed that 60 of the 89 strains could be categorized into seven clusters, each consisting of four or more strains. Based on these observations it was concluded that short nucleotide sequences bearing the variable alpha region are useful for Streptomyces species identification.

DNA, Ribosomal↗

Abnormal distribution of neurofilament L in neurons with Alzheimer's disease.

Abnormality of cytoskeletal proteins is closely related to the pathology of Alzheimer's disease. As neurofilament proteins are major cytoskeletal components of neurons, abnormality of neurofilaments is proposed in brain with Alzheimer's disease. Free-floating sections of the hippocampus with Alzheimer's disease were studied immunohistochemically, using a polyclonal antibody specifically bound to the tail region of neurofilament L (NF-L). In brains with early onset type of Alzheimer's disease, many neurons and dystrophic neurites were labeled by the antibody, while these observations were not seen in either brains with late onset type or control brains. Double immunohistochemical staining of NF-L and tau protein demonstrated that abnormal deposition of NF-L was not always accompanied with that of tau protein, indicating that the abnormal deposition of NF-L might not occur in parallel with that of tau protein. These observations suggest the involvement of neurofilament proteins on the pathology of Alzheimer's disease in a different way than tau protein.

Aged↗