[Molecular mechanism of hemoglobin function].
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Allosteric Regulation↗
Biomedical subjects
K Imai
Publications and source records attributed to K Imai.
[Detection of viability by percent thallium uptake with conventional thallium scintigraphy].
Thallium myocardial scintigraphy (TMS) is used for diagnosis of viability in infarcted myocardium before coronary revascularization. Underestimation of viability by TMS has been reported by many investigators. To evaluate viability precisely, thallium re-injection method or 24 hour delayed imaging is performed. However these techniques are not convenient and are difficult to perform in clinical practice. Percent Tl-uptake method was developed for predicting myocardial viability. To evaluate usefulness of this method, TMS was performed before and after PTCA in 23 patients with myocardial infarction. Left ventricle was divided into 3 layers, then each layer was divided into 4 segments (12 segments in total). Forth three segments showed recovery of perfusion on TMS after PTCA. Viability in infarcted myocardium is predicted by 1) redistribution (RD), 2) %Tl-uptake > or = 45% on the image immediately after exercise (TE), and 3) %Tl-uptake > or = 45% on delayed image (TD). Sensitivity was RD: 60%, TE: 90% and TD: 95% (p < 0.001 vs. RD). Specificity was RD: 74%, TE: 68%, and TD: 60% (NS). Predictive accuracy (PA) was RD: 69%, TE: 77%, TD: 73% (NS). Compared with RD, %Tl-uptake, either TE or TD, increased sensitivity with slightly improved PA, but decreased specificity slightly. Therefore %Tl-uptake would be a sensitive and useful predictor to find patients who are most likely to benefit from re-vascularization.
Adult↗
[Modified Fontan procedure for complex cardiac anomaly with nonconfluent pulmonary artery].
Modified Fontan procedure was successfully performed in two patients with complex cardiac anomaly and nonconfluent pulmonary artery. A nonconfluent portion of the pulmonary artery was interposed with a xenopericardial roll. In one patient, the central pulmonary artery was completely absent. Two-staged reconstruction of the central pulmonary artery was carried out through a left thoracotomy and a median sternotomy before the Fontan procedure. In the other patient, a juxtaductal segment of the pulmonary artery was nonconfluent. Correction of the nonconfluent pulmonary artery was performed concomitantly with the Fontan procedure. Fenestrated Fontan procedure seemed to be the beneficial modification for survival. Both patients have been day well during the midterm follow-up period.
Cardiac Surgical Procedures↗
Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.
Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intracellular LC-PTP (also called HePTP) gene is reported. The 13 to 18.5 kb genomic clones encoding human LC-PTP have been isolated. The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon. Splicing sites for exons 4 to 10, which encode the conserved catalytic PTP domain, arise almost at the same position as for the CD45 gene. This elucidation of the LC-PTP gene structure provides insight into the domain evolution of intracellular LC-PTP and transmembrane CD45, which may be generated by gene duplications of an ancestral gene.
Amino Acid Sequence↗
DNA alterations in cells from hereditary non-polyposis colorectal cancer patients.
To determine if the MCC, DCC or p53 gene is associated with susceptibility to hereditary non-polyposis colorectal cancer (HNPCC), these genes in normal cells from 12 HNPCC patients were analysed by polymerase chain reaction-single strand conformation polymorphism analysis. No changes which may alter the amino acid sequences of these genes were detected, suggesting that these genes are not associated with the susceptibility to HNPCC. Only one of nine HNPCC cancers showed mutations in the MCC and p53 genes on the same analysis. Loss of heterozygosity in chromosomes 5q, 17p, 18q and 22 was detected in four of the nine cancers, all of them being positive as to metastasis to lymph nodes. Abnormalities of the (CA)n repeat were found in six cancers, including all four without metastasis. These data indicate that tumor suppressor genes in chromosomes 5q, 17p, 18q and 22 are associated with the late stage of colorectal tumorigenesis in HNPCC, whereas the (CA)n repeat abnormalities are an early event of tumorigenesis and more essential to HNPCC.
Adult↗
Microprocessor-based memory device for ambulatory heart rate and physical activity recording.
Using microprocessor techniques, a portable digital memory device has been designed for the ambulatory monitoring of heart rate and physical activity. The device consists of a microprocessor, an ECG amplifier to record the heart rate and an accelerometer to detect the physical activity. This accelerometer is piezo-resistive and is suitable for ambulatory physical activity recording, because this sensor requires low electrical power, has high durability and wide frequency response (DC approximately 1.2 kHz). Changes in heart rates and physical activity in daily life have been successfully recorded.
Computer Storage Devices↗
Chromosomal localization of an SH2 containing tyrosine phosphatase (SH-PTP3) gene to chromosome 12q24.1.
A genomic DNA fragment, isolated from a human phage library using a human BPTP3 cDNA probe, was shown to be derived from the human SH-PTP3 (also called SH-PTP2, PTP-1D, PTP-2C, or Syp) locus. We have used fluorescent in situ hybridization (FISH) to map SH-PTP3 in chromosome band 12q24.1, a region vicinity to the second locus for autosomal dominant cerebellar ataxia (SCA2).
Amino Acid Sequence↗
[Molecular biological analyses of mucin core proteins and their clinical application].
Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 6 kinds of mucin core proteins, MUC1-6, have thus been performed. Among them, the entire structure was revealed on MUC1 and 2. MUC 1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. To date, some of the MoAbs to adenocarcinoma which were prepared for the last decade have been shown to react with the tandem repeat of MUC1(MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We could also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in a HLA-unrestricted manner, and may be of use as an adoptive immunotherapy. In addition, we have found antibody against MUC1 epitope in patients with ulcerative colitis or colon cancer. EB virus-transformed B-cell clone producing antibody against MUC1 epitope has been established from a cancer patient. Thus, MUC1 is now considered as a targeting molecule for immunotherapy. Indeed, Longenecker's group in Canada has recently tried the basic evaluation for immunotherapy using synthetic peptides of MUC1.
Amino Acid Sequence↗
A novel transcript from a pseudogene for human glucocerebrosidase in non-Gaucher disease cells.
Human glucocerebrosidase (GC)-encoding cDNA clones were isolated from a promyelocytic HL-60 cDNA library and analyzed. A novel cDNA clone was found to originate from a gene referred to as a GC pseudogene. Using the polymerase chain reaction (PCR) with primers specific for the GC pseudogene, we found that all the human cell lines examined, HL-60, K-562, WI-38, HepG2 and HeLa, expressed a pseudogene transcript. In vitro translation of RNA synthesized by transcription of the pseudogene cDNA produced a polypeptide of approximately 30 kDa.
Amino Acid Sequence↗
Site-directed mutagenesis in hemoglobin: functional and structural study of the intersubunit hydrogen bond of threonine-38(C3)alpha at the alpha 1-beta 2 interface in human hemoglobin.
To clarify the functional and structural roles of Thr-38 alpha at the alpha 1-beta 2 interface, two artificial alpha-chain mutants, in which Thr-38 alpha is replaced by Ser (Hb T38 alpha S) or Val (Hb T38 alpha V), were prepared. Thr-38 alpha is one of the highly conserved amino acid residues in hemoglobins and forms a hydrogen bond to Asp-99 beta, which is a crucial residue to stabilize the T state, via a water molecule in the deoxygenated form. We investigated their oxygen binding properties together with structural consequences of the mutations by using various spectroscopic probes. Their oxygen equilibrium curves showed small changes in the oxygen binding properties. Structural probes such as ultraviolet-region derivative and oxy-minus-deoxy difference spectra, resonance Raman scattering, and 1H-NMR spectra also indicated that the oxy and deoxy forms of these mutants show spectra characteristic of the R and T states, respectively, and the R-T transition is not very disturbed. The present structural and functional data of the mutants imply that the hydrogen bond between Thr-38 alpha and Asp-99 beta does not play a key role in stabilizing the deoxy T structure, which is in sharp contrast to the role of the hydrogen bond between Tyr-42 alpha and Asp-99 beta, and suggest that the interactions via the intersubunit hydrogen bonds are highly site-specific, depending on the amino acid residue which participates in them.
Globins↗
Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins.
We have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPH1 and PTPMEG. Northern-blot analysis of PTPH1 using poly (A)+ RNA from normal human colon tissue showed a low-abundance message of 4.3 kb. Reverse-transcriptase/polymerase-chain reaction (RT-PCR) was therefore used to detect it in a wide variety of cell lines including 9 colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPH1 mRNA was not detected only in Colo 320 cells over-expressing c-myc mRNA, among the colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5 mM sodium butyrate for 5 days, PTPH1 mRNA became detectable, concomitant with the marked decrease in the expression level of c-myc mRNA. Moreover, the chromosomal localization of PTPH1 gene was investigated by fluorescence in situ hybridization. Interestingly, PTPH1 gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists.
Base Sequence↗
Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma.
Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.
Antibodies, Monoclonal↗
Analyzing power measurement of pp elastic scattering in the Coulomb-nuclear interference region with the 200-GeV/c polarized-proton beam at Fermilab.
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Journal Article↗
Effects of intra- and intersubunit hydrogen bonds on the R-T transition in human hemoglobin as studied with alpha 42(C7) and beta 145(HC2) mutations.
To clarify the effects of specific inter- and intrasubunit hydrogen bonds on the R-T transition in human hemoglobin (Hb A), the recombination reaction of carbon monoxide with artificial mutant Hbs was measured and analyzed. One of the hydrogen bonds we focused on is formed between Tyr-42 alpha and Asp-99 beta in the alpha 1-beta 2 interface of Hb A, which is one of the hydrogen bonds characteristic of the T state. Hb His-42 alpha, in which Tyr-42 alpha is replaced by His to perturb this hydrogen bond, showed that the ligand-free R to T transition rate was decreased by 20-fold compared with that for Hb A. This mutation caused the destabilization of the transition state in the R to T quaternary structure change by about 7 kJ mol-1, indicating that the hydrogen bond between Tyr-42 alpha and Asp-99 beta plays a definite role in the R-T transition as well as in stabilization of the equilibrium T state. Hb Phe-145 beta, in which Tyr-145 beta is replaced by Phe and the intrasubunit hydrogen bond between Tyr-145 beta and Val-98 beta is lacking, also showed a slow R-T transition rate as observed in Hb His-42 alpha. The published crystallographic data suggest that this intrasubunit hydrogen bond stabilizes the transition state by reducing the freedom of motion of the C-terminus of the beta subunit and, thereby, facilitates the R-T transition.
Amino Acid Sequence↗
Oxygen equilibrium properties of asymmetric nickel(II)-iron(II) hybrid hemoglobin.
Asymmetric Ni(II)-Fe(II) hybrid hemoglobin, XL[alpha(Fe)beta(Fe)][alpha(Ni)beta(Ni)], in which the alpha 1 beta 1 dimer containing ferrous protoporphyrin IX and the complementary alpha 2 beta 2 dimer containing Ni(II) protoporphyrin IX were cross-linked between Lys-82 beta 1 and Lys-82 beta 2 by reaction with bis(3,5-dibromosalicyl) fumarate, was synthesized and characterized. We have previously shown that (i) Ni(II) protoporphyrin IX, which binds neither oxygen nor carbon monoxide, mimics a fixed deoxyheme with respect to its effect on the oxygen equilibrium properties of the counterpart iron subunits in both symmetric Ni(II)-Fe(II) hybrid Hbs [Shibayama, N., Morimoto, H., & Miyazaki, G. (1986) J. Mol. Biol. 192, 323-329] and (ii) the cross-linking used in this study little affects the oxygen equilibrium properties of hemoglobin [Shibayama, N., Imai, K., Hirata, H., Hiraiwa, H., Morimoto, H., & Saigo, S. (1991) Biochemistry 30, 8158-8165]. These remarkable features of our model allowed us to measure the oxygen equilibrium curves for the first two steps of oxygen binding to the alpha 1 beta 1 dimer within the hemoglobin tetramer. At all pH values examined, the affinities of this asymmetric hybrid for the first oxygen molecule are as low as those of native hemoglobin. The hybrid did not show cooperative oxygen binding at pH 6.4, while significant cooperativity was observed with rising pH; i.e., the Hill coefficient was increased from 1.41 to 1.53 upon a pH change from 7.4 to 8.4. The electronic absorption spectrum of Ni(II) protoporphyrin IX in the alpha 2 subunit was changed upon carbon monoxide (or oxygen) binding to the alpha 1 beta 1 dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
Cross-Linking Reagents↗
Immunohistochemical study of mucin carbohydrates and core proteins in hepatolithiasis and cholangiocarcinoma.
The expression of mucin carbohydrates [Tn, sialosyl-Tn(STn), and T antigens] and core proteins [MUCI-apomucin-related antigen (ARA) and MUC2-ARA] was examined immunohistochemically in tissues from 40 patients with hepatolithiasis and 26 patients with intrahepatic bile-duct carcinoma. Tn and STn antigens were expressed in most of the carcinomas, and were also often expressed in the atypical bile-duct epithelium of the patients with hepatolithiasis or carcinoma, whereas they were rarely or never expressed in the normal bile duct, suggesting that they are effective tumor markers. T antigen was less useful as a marker for intrahepatic bile-duct carcinoma or the atypical epithelium, because it was expressed in normal bile-duct of some cases. Regarding the expression of ARAs in the carcinomas, non-invasive bile-duct cyst adenocarcinomas with favorable prognosis either expressed no MUCI-ARA with [DF3(-), MUSEII(-) and 139H2(-)] staining pattern or expressed MUCI-ARA with [DF3(-), MUSEII(+) and 139H2(+)] staining pattern. However these tumors often expressed MUC2-ARA with [anti-MRP(+) and CCP58(+)] staining pattern. In contrast, most invasive non-papillary cholangiocarcinomas with poor prognosis expressed MUCI-ARA with [DF3(+), MUSEII(+) and 139H2(+)] staining pattern, but expressed no MUC2-ARA with [anti-MRP(-) and CCP58(-)] staining pattern. These results suggests that different apomucins are produced by bile-duct cystadenocarcinomas and cholangiocarcinomas with differing prognosis. Furthermore, expression of Tn and STn antigens is a useful indicator of malignancy in the intrahepatic duct.
Adenoma, Bile Duct↗
Atomic force microscopy of bacteriophage T4 and its tube-baseplate complex.
Bacteriophage T4 was imaged by atomic force microscopy with the finest resolution to date with a clear image of tail fibers of an estimated diameter of 2-3 nm. T4 phages were spread on a clean surface of silicon wafer and dried under air before observation with an atomic force microscope. The head, tail and tail fibers were routinely imaged with somewhat distorted dimensions. The ease of imaging isolated phage particles with a good resolution raised our expectation for the further use of AFM in biomedical applications.
Bacteriophage T4↗
Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population.
An association of lung cancer susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1. We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with "susceptible" genotypes of CYP1A1 combined with a deficient genotype of a mu-class glutathione S-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GST1 genes were identified. The patients with a susceptible homozygote of each of the MspI and Ile-Val polymorphisms contracted the carcinoma after smoking fewer cigarettes than those with other genotypes. When the GST1 polymorphism was taken into account, the cumulative cigarette amounts in combined genotyping of the two genes showed distinct differences, resulting in the lowest cigarette dose observed for the patients with a susceptible MspI or Ile-Val genotype of CYP1A1 combined with a deficient GST1 homozygote. Next, a case-control study revealed that the individuals with the susceptible MspI or Ile-Val genotype combined with deficient GST1 were at remarkably high risk with an odds ratio of 16.00 or 41.00, respectively (95% confidence interval, 3.76-68.02 or 8.68-193.61, respectively), at a low dose level of cigarette smoking.
Adult↗