Search PubMed⌕ Search

Biomedical subjects

T Kanai

Publications and source records attributed to T Kanai.

At least 127 records · Page 7Linked to original sources

Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders.

The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic resonance images of the brain and spinal cord were studied in 57 Japanese patients with multiple sclerosis (MS). Twenty-three patients clinically displayed selective involvement of the optic nerve and spinal cord and were classified as having Asian-type MS. The other 34 patients had disseminated central nervous system involvement and were classified as having Western-type MS. Patients with Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but more gadolinium-enhanced spinal cord lesions than did patients with Western-type MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101 allele were associated with Western-type MS (41.2%), but not with either Asian-type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS thus suggests the presence of two etiologically distinct diseases in Asians.

Alleles↗

A novel heterologous gene expression system in Saccharomyces cerevisiae using the isocitrate lyase gene promoter from Candida tropicalis.

We have found that the upstream region of the isocitrate lyase gene (UPR-ICL) from the n-alkane-utilizing yeast Candida tropicalis was functional in Saccharomyces cerevisiae as a novel promoter with nonfermentable carbon sources, such as oleic acid, acetate, ethanol, and glycerol/lactate. The expression of two foreign genes coding for beta-galactosidase from Escherichia coli (LacZ) and glutamate decarboxylase from rat brain was carried out under the control of UPR-ICL. Expression of LacZ was repressed by glucose and enhanced over 300-fold by acetate. When an expression vector pWI3 containing multicloning sites between UPR-ICL and the transcriptional terminator of the isocitrate lyase gene (TERM-ICL) was used, the smaller isoform of glutamate decarboxylase (GAD65) was highly produced in a soluble and active form. These results demonstrate that the novel expression system using UPR-ICL and TERM-ICL from C. tropicalis is useful for the production of heterologous proteins in S. cerevisiae.

Animals↗

Plasma hepatocyte growth factor levels are increased in systemic inflammatory response syndrome.

Interleukin-1 (IL-1), a cytokine released from macrophages by endotoxin stimulation, has been shown to upregulate the genetic expression of the hepatocyte growth factor (HGF). The present study was conducted to determine whether plasma HGF is increased in patients with systemic inflammatory response syndrome (SIRS). The plasma levels of HGF, endotoxin, and beta-glucan were measured in 41 surgical patients without hepatic diseases, 18 of whom had been diagnosed with sepsis, and 33, with nonseptic SIRS. The plasma HGF was found to be significantly increased in the 18 patients with sepsis, at 0.69 +/- 0.47 ng/ml (mean +/- SD), and in the 23 patients with nonseptic SIRS, at 0.49 +/- 0.37 ng/ml, compared to values in 40 normal controls, at 0.10 +/- 0.03 ng/ml (P < 0.001). No significant correlations were observed between the plasma levels of HGF and endotoxin (r = 0.02) or beta-glucan (r = -0.05) in any of the patients; however, plasma HGF was significantly correlated with the WBC count (r = 0.34, P < 0.05) and with total bilirubin (r = 0.45, P < 0.01). Plasma HGF was also strongly correlated with alanine transaminase (ALT) in 8 patients with ALT levels higher than 50 U/l (r = 0.70), but there was no such correlation in 33 patients with ALT levels of 50 U/l or less (r = 0.30). Thus, although the clinicopathologic significance of HGF is not well understood, the present findings indicate that plasma HGF increases in response to infection or inflammation.

Digestive System Neoplasms↗

Ciliated foregut cyst in cirrhotic liver.

We encountered a patient with a ciliated hepatic foregut cyst with accompanying liver cirrhosis, which was hard to distinguish from well-differentiated hepatocellular carcinoma. A lesion 2 cm in diameter was found in the subcapsular region of the medial segment of the liver. It was slightly hypoechoic on ultrasonography, of high attenuation on nonenhanced computed tomography (CT), of high intensity on T1-weighted spin echo images of magnetic resonance imaging (MRI), and of isointensity on T2-weighted spin echo images. It was not enhanced in the arterial phase images of MRI, and was shown as a complete perfusion defect on CT arterial portography. The cyst was enucleated and found to be filled with bloody mucinous fluid.

Carcinoma, Hepatocellular↗

Calculations of depth-dose distributions, cross sections and momentum loss.

The ability to know with precision the depth-dose, dose average LET, fluence and energy distributions is of great importance in many research fields, including therapeutic and diagnostic medicine when using heavy ion beams, as well as in space research. We have therefore developed a model and a computer code for calculating these distributions when using high energy proton or heavy ion beams. In this model, we use semi-empirical total reaction and partial cross section formulas developed by us and a new prescription to take into account the energy and momentum loss of the secondary nuclei. In this paper, we will also present an empirical equation for the total inelastic 4He-p cross section, as well as the partial cross sections for the production of 3He, 3H, 2H, p and n.

Algorithms↗

The role of DNA repair on cell killing by charged particles.

It can be noted that it is not simple double strand breaks (dsb) but the non-reparable breaks that are associated with high biological effectiveness in the cell killing effect for high LET radiation. Here, we have examined the effectiveness of fast neutrons and low (initial energy = 12 MeV/u) or high (135 MeV/u) energy charged particles on cell death in 19 mammalian cell lines including radiosensitive mutants. Some of the radiosensitive lines were deficient in DNA dsb repair such as LX830, M10, V3, and L5178Y-S cells and showed lower values of relative biological effectiveness (RBE) for fast neutrons if compared with their parent cell lines. The other lines of human ataxia-telangiectasia fibroblasts, irs 1, irs 2, irs 3 and irs1SF cells, which were also radiosensitive but known as proficient in dsb repair, showed moderated RBEs. Dsb repair deficient mutants showed low RBE values for heavy ions. These experimental findings suggest that the DNA repair system does not play a major role against the attack of high linear energy transfer (LET) radiations. Therefore, we hypothesize that a main cause of cell death induced by high LET radiations is due to non-reparable dsb, which are produced at a higher rate compared to low LET radiations.

Animals↗

LET dependence of cell death, mutation induction and chromatin damage in human cells irradiated with accelerated carbon ions.

We investigated the LET dependence of cell death, mutation induction and chromatin break induction in human embryo (HE) cells irradiated by accelerated carbon-ion beams. The results showed that cell death, mutation induction and induction of non-rejoining chromatin breaks detected by the premature chromosome condensation (PCC) technique had the same LET dependence. Carbon ions of 110 to 124keV/micrometer were the most effective at all endpoints. However, the number of initially induced chromatin breaks was independent of LET. About 10 to 15 chromatin breaks per Gy per cell were induced in the LET range of 22 to 230 keV/micrometer. The deletion pattern of exons in the HPRT locus, analyzed by the polymerase chain reaction (PCR), was LET-specific. Almost all of the mutants induced by 124 keV/micrometer beams showed deletion of the entire gene, while all mutants induced by 230keV/micrometer carbon-ion beams showed no deletion. These results suggest that the difference in the density distribution of carbon-ion track and secondary electron with various LET is responsible for the LET dependency of biological effects.

Carbon↗

HLA-DQ-binding peptide motifs. 1. Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthritis-susceptible and non-susceptible haplotypes.

The frequency of the HLA-DR4-DQ4 haplotype (DRB1(*)0405-DQA1(*)0302-DQB1(*)0401) is significantly increased in Japanese patients with rheumatoid arthritis (RA) and DRB1(*)0405-binding peptide motifs were identified in our previous studies. To clarify the DQ4-binding peptide motifs, the primary structure of DQ4-binding peptides was determined by affinity-based selection of a phage random peptide library. Analog peptides of a high-affinity DQ4 binder revealed that two major anchors (VxxxxxxxR; where x is any amino acid) play an essential role in binding to DQ4. The affinity of synthetic VAAAAAAAR-based analog peptides showed that substituting V to W, G, L, I, M, P, F, Y or A and R to H, M, L, I or V allows binding. The involvement of the ninth residue of the peptides, especially Arg, was critical for high-affinity binding. In comparison with other class II-binding peptide motifs reported to date, peptide motifs for DQ4 were unique, in that Gly and Pro are allowed as low-affinity N-terminal anchors. Interestingly, 94 putative DQ4-binding motifs were detected in the human type II collagen molecule, since it is composed of (Gly-X1-X2)n and is rich in R and P at positions X2. However, no significant differences were observed between the affinities of the collagen-derived peptides with DR or DQ molecules of RA-susceptible DR4-DQ4 and with those of non-susceptible DR4-DQ8 (DRB1(*)0406-DQA1(*)0301-DQB1(*)0302) haplotypes, indicating that the susceptibility to RA is not a simple immune response gene phenomenon specific to collagen. The immunogenetic implications of the unique peptide motifs for DQ are discussed.

Amino Acid Sequence↗

Determination of the presence of interleukin-6 in bile after orthotopic liver transplantation. Its role in the diagnosis of acute rejection.

OBJECTIVE: The authors evaluated the significance of interleukin-6 (IL-6) in bile in the diagnosis of acute rejection after liver transplantation. SUMMARY BACKGROUND DATA: Interleukin-6 in blood has not been shown to be useful as a marker of acute rejection in clinical liver transplantation. In a rat liver transplantation model, the authors have found that bile IL-6 levels correlated well with the severity of rejection as determined histologically, whereas kinetics of serum IL-6 differed among rats without any definite feature related to graft rejection. METHODS: Fifty-one patients who underwent orthotopic liver transplantation between May 1990 and February 1991 at the University of California, Los Angeles, were included in the study. After liver transplantation, bile and blood were collected daily, and IL-6 levels were measured by the enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 increased to 1228 +/- 317 pg/mL on the day of transplantation and decreased to 50 pg/mL or less within 48 hours. Patients who had uneventful postoperative courses had low levels of bile IL-6 throughout their hospitalization. In patients with acute rejection, bile IL-6 significantly increased (1090 +/- 990 pg/mL; p<0.05), but decreased in response to antirejection therapy. In patients who had liver dysfunction due to ischemic change or sepsis, bile IL-6 did not increase. Patients with cholangitis had significantly increased levels of bile IL-6 (146 +/- 47; p<0.05). Interleukin-6 in blood increased with many kinds of complications other than rejection and seemed to be less specific than that in bile. CONCLUSIONS: Measurement of IL-6 in bile may be a useful, noninvasive tool for diagnosing acute rejection.

Acute Disease↗

Changes in myocardial lactate metabolism during ramp exercise in patients with effort angina and microvascular angina.

Changes in myocardial lactate metabolism during ramp exercise were investigated through great cardiac vein catheterization in 15 patients with effort angina (EA) and 7 patients with microvascular angina (MVA). The exercise test was performed using a supine bicycle ergometer. Blood samples were obtained from the great cardiac vein (GCV) and the radial artery each minute during exercise. Patients in the EA group showed a point at which the lactate extraction ratio (LER) and the ST level decreased rapidly during exercise. This point was clearly recognized in 12 of 13 patients, and may represent the ischemic threshold. Both the LER and ST level showed similar changes during exercise, and these values were significantly different between the ischemic threshold and peak exercise (p < 0.01). Both the LER and ST level were strongly correlated with the duration of exercise until the threshold (r = 0.703). In the MVA group, both the LER and ST level during exercise continuously decreased throughout exercise without an ischemic threshold in all of the subjects. Endomyocardial biopsy revealed sclerosis of small arteries in the myocardium in all of the patients. In both effort angina and microvascular angina, a close correlation was noted between the change in ST and that in the myocardial lactate extraction ratio.

Adult↗

[Biological effect of carbon beams on cultured human cells].

This study was performed to determine the biological effect of carbon beams on 13 human tumor cells, in comparison with 200 KVp X-rays. Carbon beams were generated by the Riken Ring Cyclotron. The RBE (relative biological effectiveness) values were distributed from 1.46 to 2.20 for LET of 20 ke V/micron, and 2.29-3.54 for 80 keV/micron. The RBEs were increased in all cell lines as the LET of carbon beams was increased from 20 to 80 keV/micron. There was no significant difference in radiosensitivity between cells from adenocarcinoma and those from squamous cell carcinoma. The relationship between the radiosensitivity of cells to X-rays and RBE was analyzed, but no significant correlation was suggested. Several survival curves of 20-40 keV/micron carbon beam irradiation showed the initial shoulders and the recovery ratios between two split doses were determined. Recovery was observed for LET of 20 keV/micron but not for that of 40 keV/micron. Furthermore, recovery ratios were 1.0-1.8, smaller than those for X-rays (1.5-2.4).

Adenocarcinoma↗

A new technique for exposing Calot's triangle during laparoscopic surgery: usefulness of extracorporeal lifting of the round ligament and gallbladder.

We developed a maneuver for holding and lifting the intraperitoneal organs from the extracorporeal side using a new instrument, the leading bar, by which we could guide the tape or the thread to the outside of the abdomen. In the case of cholecystolithiasis with a thickened wall or a stone stuck in the neck, we lifted the round ligament and gallbladder for better exposure of Calot's triangle, using the tape or thread through the abdominal wall to the extracorporeal side, and then clamped them with Kocher's forceps. With this technique, a good view of Calot's triangle was maintained so that the surgeon could expose the cystic duct easily and safely using both hands.

Cholangiography↗

[Mutation induction by heavy ion beams and X-rays: analysis with cultured cell line].

This study was performed to determine the biological effects of heavy ion beams on cultured cells. V79 cells were irradiated with carbon or neon beams or X-rays, and cell survivals was calculated by the colony assay method. The Do values for 150 kVp X-rays, 20 keV/micron and 80 keV/micron carbon beams, and 80 keV/micron neon beams were 2.2Gy, 1.8Gy, 1.0Gy and 1.4Gy, respectively. After 7-10 day expression periods, the mutation frequencies at the hypoxanthine-guanine phosphribosyl transferase (hprt) locus were analyzed from the numbers of colonies formed in media supplemented with 6-thioguanine. An extremely higher frequency of mutation was observed with heavy ion beams compared with X-rays. Both cell killing effect and the mutation induction were enhanced when the LET of carbon beams was increased from 20 to 80 keV/micron. These results mean that carbon beams had a stronger cell-killing effect than X-rays, but also carried a high risk of mutation induction. On the other hand, neon beams yielded cell survival curves similar to those of carbon beams, but they had a smaller mutation induction effect than carbon beams. The effect of fractionated irradiation (3 hr interval) on cell survival and mutation frequency were also examined. When cells were irradiated with X-rays, cell survival was increased by fractionation, but the mutation frequency was not modified. Irradiating cells with fractionated carbon beams, survival curves were not affected, but mutation frequency was reduced.

Animals↗

[An investigation of the factors influencing serum pepsinogen levels--sex, age, smoking, drinking].

BACKGROUND: Until now, the influence of sex, age, smoking, drinking on serum pepsinogen levels has been assessed by single regression analysis. However, the influence of those factors on pepsinogen levels should be assessed exactly by multiple regression analyses. SUBJECTS AND METHODS: 891 subjects were collected from by questionnaire and serum tests. Analyses were done with serum pepsinogen I (PG I), pepsinogen II (PG II) and pepsinogen I/II ratio (PG I/II) as a criterion variable and as categorized explanatory variables, sex, age, current or past smoking habit, and current drinking habit. And analyses are done by Mann-Whitney U test, correlation coefficient, single regression method, multiple regression method. RESULTS: PG I level is significantly higher in men than in women by Mann-Whitney U test. But the effect of sex factor is not remarkable by multiple regression analyses. PG II level increased and PG I/II level decreased with progression of age by all analyses methods. Current or past smoking elevates PG I level by Mann-Whitney U test, but current smoking dose and past smoking amount showed no dose-dependent associations with PG I level. Current drinking elevates PG I level by Mann-Whitney U test, but current drinking dose showed no dose-dependent associations with PG I. However, the effects of current smoking and current drinking to serum PG levels is not so large by multiple regression analyses. CONCLUSION: The effects of sex, current smoking and current drinking to serum PG levels are not remarkable by multiple regression analyses. Significantly, PG II level increased and PG I/II level decreased with progression of age. Therefore it may not be necessary to consider the effects of sex, smoking habit and drinking habit when serum pepsinogen levels are used as markers for gastric cancer.

Adult↗

A comparison of biological effects of modulated carbon-ions and fast neutrons in human osteosarcoma cells.

PURPOSE: To compare the biological effects of a 135 MeV/u carbon-ion beam and 13 MeV fast neutron beam using human osteosarcoma cells. METHODS AND MATERIALS: We have studied the clonogenic cell survival, recovery of potentially lethal damage (PLD) in plateau phase cells, and spheroid cure in multicellular spheroid after irradiation at various positions in the plateau and spread out Bragg peak (SOBP) of a 135 MeV/u carbon-ion beam and with 13 MeV neutrons. The carbon beam had a 4-cm range in water and a range filter was used to produce a 3-cm extended-peak region. The reference radiation was 137Cs gamma-rays. RESULTS: The relative biological effectiveness (RBE) values for 10% survival level of plateau phase cells for carbon-ions at the position of plateau, proximal peak, midpeak, and distal peak within the SOBP, and neutrons were 1.71, 2.48, 2.63, 3.47, and 2.29, respectively. Corresponding RBE values at 1% level were 1.64, 1.93, 2.06, 2.49, and 2.05. The extent of recovery from PLD was reduced after carbon-ions at proximal peak, midpeak, and distal peak, and neutrons, although not substantially reduced after carbon-ions at plateau. The RBE values for 50% spheroid cure level of spheroids for carbon-ions at the position of plateau, proximal peak, midproximal peak, middistal peak, and distal peak within the SOBP, and neutrons were 1.69, 1.88, 1.87, 1.94, 2.03, and 1.90, respectively. CONCLUSIONS: The biological parameters measured all indicate an approximately comparable biological effectiveness between 75-80 KeV/microns carbon-ions of the SOBP and 13 MeV neutrons in the human tumor model studied in vitro.

Carbon↗