Search PubMed⌕ Search

Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 73 records · Page 4Linked to original sources

Primary adenocarcinoma of the duodenum demonstrated by ultrasonography.

A 57 year-old man presented with abdominal discomfort and melena. Abdominal ultrasonography clearly revealed a duodenal tumor as a hypoechoic mass in the transverse segment of the duodenum. The lesion was a 4 x 4-cm oval mass with partial concavity, an irregular surface, high-level central echoes, and a hypoechoic periphery. After confirmation of the diagnosis of duodenal carcinoma, a pylorus-preserving pancreatoduodenectomy was performed curatively. Pathological examination revealed moderately differentiated tubular adenocarcinoma partially invading the pancreatic parenchyma. Ultrasonography can be used to detect lesions of the transverse segment of the duodenum as the first imaging procedure.

Adenocarcinoma↗

Early stage gastric MALT lymphoma with high-grade component cured by Helicobacter pylori eradication.

A 68-year-old woman was diagnosed with gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) type with a high-grade component. Surgical treatment was recommended because of the presence of the high-grade component, but she refused surgery. As an alternative, she received Helicobacter pylori eradication treatment, which successfully induced regression of the lymphoma. She shows no sign of recurrence endoscopically and histologically, as of 29 months after the eradication treatment. Moreover, the B-cell monoclonality and Helicobacter pylori infection demonstrated at diagnosis has disappeared. This is one of the rare cases of gastric lymphoma of the MALT type with a high-grade component cured by Helicobacter pylori eradication alone.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors.

By examining 19 human cell lines derived from brain tumors for altered expression of expressed sequence tags (ESTs) in chromosomal band 4q21-22, we detected loss of expression, in 10 cell lines, of two sequences, WI6336 and WI7913. Both corresponded to the c-Jun NH2-terminal kinase (JNK) 3. In the present study, genomic cloning revealed that the JNK3 gene consists of 14 exons interrupted by 13 introns; its transcription-initiation site is within exon 3 and the termination codon lies in exon 14. Fluorescence in situ hybridization (FISH) and radiation-hybrid mapping confirmed the gene to 4q21-22. Together with prior evidence that, in JNK3-deficient mice, the JNK3 signaling pathway mediates apoptosis in central nervous tissue, our results suggest that loss of expression of the JNK3 gene may play an important role in the development of brain tumors in humans.

Base Sequence↗

Human calcitonin receptor-like receptor for adrenomedullin: genomic structure, eight single-nucleotide polymorphisms, and haplotype analysis.

Adrenomedullin (ADM), a peptide characterized by persistent hypotensive activity, is thought to be involved when the control mechanism of blood pressure is deranged, because its plasma concentration is upregulated in hypertensive patients. The receptor for ADM, a molecular complex consisting of calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 2 (RAMP2), is activated through a unique intracellular transport mechanism. By analyzing the nucleotide sequences of bacterial artificial chromosome (BAC) clones, we have established that the gene encoding CRLR is spread over a genomic distance of 103,145 bases; it contains 15 exons interrupted by 14 introns, including 1 that spans more than 60 kilobases. Exons 1-3 constitute the 5' noncoding region; exons 4 through 15 are coding elements, of which exons 8 to 14 encode seven transmembrane domains. Eight novel single-nucleotide polymorphisms (SNPs) and their allelic frequencies in the Japanese population were found by direct sequencing of 32 alleles; two SNPs were in the 5' flanking region, one in exon 2, and the other five around intron-exon junctions. Eight haplotypes were constructed using these alleles in our Japanese population sample. The data establish a basis for investigations to detect molecular variants in the ADM receptor that might alter control of blood pressure and confer on individuals a predisposition to essential hypertension.

Alleles↗

Molecular cloning, tissue expression, and chromosomal assignment of a novel gene encoding a subunit of the human signal-recognition particle.

Human cancers derived from breast, esophageal, or ovarian tissues frequently show allelic losses on chromosome band 17q25. Moreover, a locus responsible for hereditary focal nonepidermolytic palmoplantar keratoderma, a condition associated with esophageal cancer (TOC; tylosis with oesophageal cancer), has been mapped to the same band. During efforts to sequence, by shotgun methods, a 1-Mb target region that we had defined as the DNA segment harboring the putative tumor suppressor gene(s) involved in these events, we identified a novel cDNA. The full-length cDNA is 2495bp long and is expressed predominantly in skeletal muscle, heart, kidney, and placenta. The predicted product, a 627-amino-acid protein, exhibited significant sequence homology to the canine 68-kd subunit of the signal recognition particle that has been implicated in the transport of secreted and membrane proteins to the endoplasmic reticulum for proper processing. We confirmed the location of this gene at chromosome 17q25.1 by radiation-hybrid mapping and by fluorescence in situ hybridization.

Amino Acid Sequence↗

Identification of DMC1, a novel gene in the TOC region on 17q25.1 that shows loss of expression in multiple human cancers.

Frequent allelic losses within chromosomal band 17q25.1 in a variety of human cancers have suggested the presence of one or more tumor suppressor genes in this region. Furthermore, a genetic locus responsible for familial focal nonepidermolytic palmoplantar keratoderma, a condition associated with cancer of the esophagus, lies in the same region. This esophageal-cancer susceptibility locus, TOC (tylosis with oesophageal cancer), might be a target of deletions at 17q25.1 in multiple types of malignancy. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine cancer cell lines for alterations in the expression of transcripts from this portion of 17q, we identified a novel gene that we designated DMC1 (downregulated in multiple cancer-1). The full-length cDNA is 3293bp long. Its putative product is an integral membrane protein of 788 amino acids, belonging to the class of so-called 'inside-out" membrane proteins; it lacks a signal sequence but contains an N-terminal cytoplasmic domain, a single transmembrane peptide, and a C-terminal extracellular domain. We documented loss of expression of DMC1 in 2 of 10 breast-cancer cell lines, in 7 of 10 cervical-cancer lines, in 7 of 13 hepatocellular-cancer lines, in 3 of 7 lung-cancer lines, in 3 of 6 thyroid-cancer lines, in 2 of 6 gastric-cancer lines, and in 2 of 4 renal cell-cancer lines. Our results suggest that loss of expression of the DMC1 gene at 17q25.1 may play an important role in the development of cancers in a broad range of human tissues.

Amino Acid Sequence↗

Nine novel single-nucleotide polymorphisms in the integrin beta4 (ITGB4) gene in the Japanese population.

We identified nine single-nucleotide polymorphisms (SNPs) in the human integrin beta4 (ITGB4) gene (17q24-q25), which encodes a cell-surface receptor, by screening all exons and exon-intron boundaries. Seven of these SNPs were present in coding regions and two in intronic sequences; four of the coding SNPs involved amino-acid substitutions. As the gene is implicated in the tumorigenesis of breast cancers, the polymorphic sites will serve as useful markers not only for distinguishing alleles in loss of heterozygosity (LOH) analyses but also for studying genetic susceptibility to malignancies in humans.

Antigens, CD↗

Evaluation of 4-nonylphenols and 4-tert-octylphenol contamination of fish in rivers by laboratory accumulation and excretion experiments.

Laboratory accumulation and excretion experiments of 4-nonylphenols (NP) and 4-tert-octylphenol (OP) were performed for killifish (Oryzias latipes). The bioconcentration factors (BCF, wet weight) in the whole fish were mean +/- SD of 167 +/- 23 (n = 4) for NP and 261 +/- 62 (n = 4) for OP. The biological half-lives in the whole fish were 9.9 h for NP and 7.7 h for OP. Parallel to the laboratory experiments, field survey on the chemicals contamination for water and ayu fish (Plecoglossus altivelis) from rivers flowing into Lake Biwa was performed. The contamination was not so high in agreement with the laboratory experimental data and the field BCF values (wet weight) in the ayu fish were 21 +/- 15 (n = 8) for NP and 297 +/- 194 (n = 3) for OP.

Animals↗

Microbial-ecological significance of sulfide precipitation within anaerobic granular sludge revealed by micro-electrodes study.

Micro-electrodes were applied to anaerobic granular sludge, which was developed in a UASB reactor, to examine intra-granule profiles with respect to pH, glucose and sulfide. When glucose was employed as a bulk liquid substrate, the micro-electrodes study demonstrated the pH behavior along granule depth: pH decrement at the granule exterior portion due to acid formation (buildup of acidity), and subsequent pH increment at the granule inner portion due to the consumption of acid (buildup of alkalinity). Sulfide micro-electrode proved sulfate reduction that mostly occurred at the granule exterior portion. Chemical equilibrium consideration evidently explained the occurrence of ferric sulfide predominantly in the interior portion, which accounts well for the morphology of a representative double-layered structure of granules grown on a low level of sulfite. Inorganic elements distribution within anaerobic granule was examined by electron probe X-ray micro analysis (EPMA) and ICP methods. The presence of crystalline calcium carbonate (calcite) was identified by X-ray diffraction analysis.

Bacteria, Anaerobic↗

Prognosis of acute acoustic trauma: a retrospective study using multiple logistic regression analysis.

OBJECTIVE: The prognosis for acute acoustic trauma (AAT) is difficult to predict. Multiple logistic regression analysis was used in this study to determine which factors were most strongly related to outcome for patients with AAT. METHODS: The study group was comprised of 52 patients (52 ears). Separate analyses were performed on the no change and partial recovery groups, and on the no change and full recovery groups. The following eight factors were examined as explanatory variables, age; number of days before the start of treatment; use of earplugs; drug therapy (adrenocortical hormones, low molecular weight dextrans, and vitamin B12), mean hearing levels at 0.5, 1, and 2 kHz (pure tone average, PTA), and mean hearing levels at 4 and 8 kHz (high tone average, HTA). RESULTS: Factors determined to be most strongly related to outcome were the number of days before the start of treatment, PTA, and HTA. No significant relation to outcome was determined for the five following factors, age; use of earplugs; and drug therapy (adrenocortical hormones, low molecular weight dextrans, and vitamin B12). CONCLUSION: Our results will increase the ability to prognosticate the outcome for AAT.

Acute Disease↗

Spiral CT findings in septic pulmonary emboli.

OBJECTIVES: The aim of the study was to determine the characteristics of septic pulmonary emboli and their prevalence on spiral computed tomographic (CT) scans. METHODS AND MATERIALS: We evaluated 65 lesions on spiral CT scans in ten patients with septic pulmonary emboli. Spiral CT scans (10-mm collimation) were obtained at 10-mm intervals from the lung apex to the diaphragm and were compared with posteroanterior chest radiographs obtained within 24 h after CT scanning. RESULTS: Only 21 (32%) of the 65 lesions detected on CT scans were also detected on chest radiographs. Peripheral nodules (39 lesions (60%)) were seen in all ten patients, wedge-shaped peripheral lesions (15 lesions (23%)) in nine patients, and infiltrates (11 lesions (17%)) in four patients. Subpleural lesions (45 lesions (69%)) and feeding vessels (35 (54%)) were found in all patients, and cavitary lesions (seven lesions (11%)) were seen in four patients. Subpleural peripheral nodules and wedge-shaped peripheral lesions were seen in nine patients. Thirty-two lesions (49%) ranged in diameter from 10 to 19 mm, and 59 lesions (91%) were less than 30 mm. CONCLUSIONS: Spiral CT is useful in detecting septic pulmonary emboli. On spiral CT subpleural peripheral nodules and wedge-shaped peripheral lesions less than 30 mm in diameter are often found in patients with septic pulmonary emboli.

Adult↗

Recent advances in methane fermentation technology.

In the past two decades, a number of biotechnologies for anaerobic (methanogenic) wastewater treatment have been created, and practical applications of these processes are now being extended to more recalcitrant wastewaters and to wastewaters at extreme temperatures. Our knowledge of methanogenic organic degradation associated with bioreactors is also accumulating at a rapid rate. The recent advancement of such fundamental understanding is attributed to modern molecular biology techniques applied to the study of microbial communities and to continuous challenges to the cultivation of many important but recalcitrant anaerobes in bioreactors.

Anaerobiosis↗

Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists.

In the previous paper, we described a series of 2-phenylethenesulfonamide derivatives, a novel class of ET(A)-selective endothelin (ET) receptor antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy derivative (2b). In this paper, we wish to report further details of structure-activity relationships (SARs) of the two regions of the molecule in compound 2b, which were the alkoxy region at the 6-position of the core pyrimidine ring and the 2-phenylethenesulfonamide region. In these modifications, replacement of the 2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2-phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (6l) or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A) binding affinity and ET(A) selectivity. Among them, compound 6e showed further improvement in oral activity compared to 2b. After oral administration, compound 6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3mg /kg with a duration of >6.5h. Compound 6e also exhibited a potent antagonistic activity in the pithed rats.

Administration, Oral↗

2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A(2B) adenosine receptor.

A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The m-primary benzamide derivative 15f was the most potent compound (IC(50)=0.017 microM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity. The IC(50) values in rat hepatocyte glucose assay correlated well with the IC(50) values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2)=0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor.

Adenine↗

Sonophotocatalytic decomposition of water using TiO(2) photocatalyst.

Sonophotocatalytic reaction is a photocatalytic reaction with ultrasonic irradiation or the simultaneous irradiation of ultrasound and light with a photocatalyst. The possibility of the effect of hybrid of sonochemical and photocatalytic reactions was examined. Liquid water was hardly decomposed to H(2) and O(2) by photocatalysis or sonolysis, independently. In order to decompose water, powdered TiO(2) photocatalyst suspended in distilled water should be simultaneously irradiated by light and ultrasound. This sonophotocatalytic reaction was effective on the decomposition of water to H(2) and O(2).

Journal Article↗

Influence of TT virus on the clinical course of alcoholic liver disease.

The sera of 43 patients with alcoholic liver disease (ALD) who abstained from alcohol for 4 weeks, were tested for TT virus (TTV) DNA by polymerase chain reaction (PCR) using three different primer pairs (UTR PCR, N22 PCR and genotype-1 PCR). The clinical course of the TTV DNA-positive and -negative groups was compared. By UTR PCR which detects all TTV genotypes, TTV DNA was detected in 40 patients (93%). N22 PCR which detects primarily TTV genotypes 1-6, detected TTV DNA in 17 patients (40%). The alanine aminotransferase (ALT) level 4 weeks after the start of abstinence was significantly higher and the rate of change in ALT {[(ALT on admission-ALT 4 weeks after abstinence)/(ALT on admission)]x100} was lower in the patients who were positive by N22 PCR, than in those who were negative by N22 PCR. Twelve patients (28%) were positive for TTV genotype 1. In the TTV genotype 1-positive group, the ALT 4 weeks after the start of abstinence was significantly higher, and the improvement rates of ALT, gamma-glutamyl transpeptidase and alkaline phosphatase levels were lower than those in the TTV genotype 1-negative group. These results suggest that certain genotypes of TTV may interfere with the improvement of liver function following the start of abstinence in ALD patients.

Journal Article↗

Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients?

The aim of this study was to investigate the effect of various medications other than interferon (IFN) on liver fibrosis in chronic hepatitis C (CH-C) patients, and the results were compared with those obtained in CH-C patients without therapy. Fifty CH-C patients (32 men and 18 women; mean age 58.5 years) without previous IFN therapy, who randomly received medicines other than IFN such as Stronger Neo-Minophagen C, Ursodeoxycholic acid and a herbal medicine, Sho-saiko-to (TJ-9) (Group I), and as a control group, 45 CH-C patients (27 men and 18 women; mean age 56.6 years) without therapy (Group II) were examined. All patients had persistent alanine aminotransferase (ALT) elevation more than 6 months before this study and were also subdivided into three subgroups according to different pattern of ALT during the observation period, i.e. (a): persistently ALT<60 IU/l (below about twice the upper limit of normal range); (b): persistently ALT>/=60 IU/l; and (c) other than (a) and (b). All patients were biopsied twice before starting this study and during observation period and the liver fibrosis was compared between them by staging in each case. When the fibrosis stage was the same between two specimens, we determined whether the degree of fibrosis had improved or worsened by computed image analysis. Blood tests for fibrosis marker, serum aminoterminal peptide of type III procollagen (P III P) and liver enzyme such as albumin (Alb) and zinc turbidity test (ZTT) levels, and platelet (Plt) counts were also examined on the two times of liver biopsy. As a result, there were no significant differences in fibrotic improvement rate when assessed by both staging only and staging together with fibrotic ratio, determined by computed image analysis and also in yearly change of P III P (P/Y) and fibrosis (F/Y), the changed rate of Alb, ZTT levels and Plt counts between Group I and Group II, except for P/Y in subgroup (a) which was rather higher in Group I than in Group II. There were also no significant relationship between the changes of histological activity and fibrosis staging in both groups. In conclusion, other medications than IFN could not significantly improve both liver fibrosis and its associated laboratory data irrespective of ALT levels in CH-C patients as compared to the control group during average 3 years' follow-up period.

Journal Article↗

Influence of TT virus infection on the thrombocytopenia of patients with chronic liver disease.

TT virus (TTV) can replicate not only in the liver but also in hematopoietic cells. To investigate the possible influence of TTV infection on the hematological parameters of patients with chronic liver disease, serum samples from 581 patients with chronic, viral or non-viral liver disease were tested for TTV DNA by polymerase chain reaction (PCR). PCR was performed by two distinct methods using N22 primer pairs (N22 PCR), which detect primarily the four major TTV genotypes (1-4), and using genotype 1-specific primers (Genotype 1-PCR). Thirteen hematological parameters measured in routine laboratory tests were compared among the patients who were positive or negative for TTV infection. The platelet count was significantly lower in the N22 PCR-positive group than in the N22 PCR-negative group among the 189 patients with chronic hepatitis C (CH-C) and among the 40 patients with chronic hepatitis without serological markers of ongoing hepatitis B virus or hepatitis C virus infection (CH-NBNC) (P<0.0001, P<0.005, respectively). Similarly, among the patients with CH-C or CH-NBNC, the platelet count was significantly lower in the TTV genotype 1-positive group than in the TTV genotype 1-negative group (P<0.001, P<0.05, respectively). The reduced platelet count of the TTV DNA-positive group was observed in every fibrotic stage of chronic hepatitis (F0-F3). These results suggest that infection of TTV of certain genotypes including genotype 1 may worsen the thrombocytopenia of patients with CH-C or CH-NBNC, irrespective of the degree of hepatic fibrosis.

Journal Article↗