Biomedical subjects

M Hosokawa

Publications and source records attributed to M Hosokawa.

At least 55 records · Page 3Linked to original sources

PubMed2001

Endoscopic screening for early esophageal cancer by iodine staining in patients with other current or prior primary cancers.

BACKGROUND: Although early diagnosis of esophageal carcinoma is an important determinant of outcome, early stage carcinomas are rarely detected on routine endoscopic examination. Iodine staining may be useful in the detection of early stage esophageal carcinoma, especially in high-risk populations. In a prior study, 29.2% (68/233) patients with superficial esophageal carcinoma (SEC) undergoing resection at our hospital had other nonesophageal primary carcinomas, suggesting that patients with nonesophageal primary cancers are at increased risk for the development of esophageal cancer. The aim of the current study was to determine whether endoscopic screening with iodine staining is useful for the detection of SEC in patients with a history of non-esophageal cancers. PATIENTS AND METHODS: In a prospective study, 331 patients with nonesophageal primary cancers were screened for esophageal cancer by endoscopic examination with iodine staining. All patients were men 55 years of age or older. RESULTS: Nine patients (2.7%) with SEC were identified. Among these patients, 7 with mucosal cancer were treated by endoscopic mucosal resection, and 2 with submucosal cancer were treated by surgical resection or radiation therapy. Five patients (1.5%) were found to have cancer confined to the epithelium or the lamina propria. These lesions were difficult to detect by conventional endoscopic screening and were cured by endoscopic mucosal resection. After exclusion of 51 patients with head and neck cancer, the incidence of SEC was still 2.1% (6/280), higher than reported in prior screening studies. CONCLUSIONS: All men with a history of nonesophageal primary cancers should undergo endoscopic screening for esophageal cancer. Endoscopic iodine staining in such patients may be useful in screening for early stage esophageal carcinoma.

Aged↗

PubMed2001

Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection.

BACKGROUND: Endoscopic mucosal resection (EMR) is being used increasingly to treat early stage esophageal carcinoma. However, the preserved esophageal mucosa may be the source of new lesions. The aims of this study were to analyze the frequency of metachronous esophageal carcinoma after EMR and to determine whether minute iodine unstained areas often associated with squamous cell carcinoma develop into carcinoma. METHODS: Eighty-two patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine staining pattern at initial EMR, they were divided into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were followed by endoscopy with iodine staining (group U: median 39 months, range 12 to 71 months; group S: median 38 months, range 14 to 68 months). RESULTS: In total, 12 (14.6%) of 82 patients were found to have metachronous esophageal carcinoma during follow-up, including 6 (37.5%) of 16 patients in group S. The cumulative proportion of metachronous carcinoma-free subjects was significantly lower in group S than group U (p = 0.0048). CONCLUSIONS: Primary esophageal carcinoma develops frequently in patients who have undergone EMR for esophageal squamous carcinoma. The high frequency of metachronous carcinoma may be attributed to field carcinogenesis. Careful long-term endoscopic observation is required for patients who undergo EMR for esophageal carcinoma, especially those with scattered-type iodine staining of the background mucosa.

Aged↗

PubMed2001

Progress of lignification mediated by intercellular transportation of monolignols during tracheary element differentiation of isolated Zinnia mesophyll cells.

Tracheary element (TE) differentiation is a typical example of programmed cell death (PCD) in higher plants, and maturation of TEs is completed by degradation of all cell contents. However, lignification of TEs progresses even after PCD. We investigated how and whence monolignols are supplied to TEs which have undergone PCD during differentiation of isolated Zinnia mesophyll cells into TEs. Higher densities of cell culture induced greater lignification of TEs. Whereas the continuous exchanging of culture medium suppressed lignification of TEs, further addition of coniferyl alcohol into the exchanging medium reduced the suppression of lignification. Analysis of the culture medium by HPLC and GC-MS showed that coniferyl alcohol, coniferaldehyde, and sinapyl alcohol accumulated in TE inductive culture. The concentration of coniferyl alcohol peaked at the beginning of secondary wall thickening, decreased rapidly during secondary wall thickening, then increased again. These results indicated that lignification on TEs progresses by supply of monolignols from not only TEs themselves but also surrounding xylem parenchyma-like cells through medium in vitro.

Asteraceae↗

PubMed2001

Preoperative computed tomography diagnosis of non-recurrent inferior laryngeal nerve.

OBJECTIVE: The non-recurrent inferior laryngeal nerve (NRILN) is a nerve anomaly that is associated with the developmentally aberrant subclavian artery. Thus, it is possible to predict NRILN by preoperative diagnosis of an aberrant subclavian artery. Preoperative recognition of the NRILN should be advantageous in the prevention of intraoperative nerve damage. The purpose of this study was to assess the possibility of diagnosis of an aberrant subclavian artery by computed tomography (CT) of the neck, which is often performed before thyroid surgery. METHODS: We retrospectively studied the preoperative CT films from 594 thyroid or esophageal surgery patients treated in our hospital between May 1995 and December 2000. An NRILN was identified intraoperatively in 6 of these patients, and a right recurrent inferior laryngeal nerve (RILN) was observed in 588 of these patients. We evaluated whether the brachiocephalic artery could be identified on the CT scan and classified the positional relationship between the right subclavian artery and the tracheoesophagus into three types. RESULTS: The brachiocephalic artery was identified on the CT films in 158 cases, all of which were cases of RILN. The right subclavian artery was detected on the ventral side of the membranous wall of the trachea in all 588 RILN cases, whereas it was detected on the dorsal side in all 6 NRILN cases. CONCLUSIONS: It was possible to predict an aberrant subclavian artery by identifying the brachiocephalic artery and position of the right subclavian artery on the CT film of the neck. When an anomaly of the subclavian artery is thus preoperatively detected, NRILN can be preoperatively predicted, which likely will enable prevention of vocal cord paralysis.

Aged↗

PubMed2001

Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.

The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARgamma ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present time-course study was conducted to investigate possible modifying effects of a PPARgamma ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg / kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg / kg b.w.)-induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARgamma ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.

Animals↗

PubMed2001

Synergistic effects of highly unsaturated fatty acid-containing phosphatidyl-ethanolamine on differentiation of human leukemia HL-60 cells by dibutyryl cyclic adenosine monophosphate.

Highly unsaturated fatty acid-containing phospholipid (HUFA-PL) has many nutritional and medical applications. We investigated the effect of HUFA-PL on differentiation of human leukemia HL-60 cells induced by dibutyryl cyclic adenosine monophosphate (dbcAMP). HUFA-containing phosphatidylethanolamine (HUFA-PE), such as salmon testis PE, significantly enhanced dbcAMP-induced cell differentiation. A combined treatment of 200 mM dbcAMP with 50 mM HUFA-PE increased the nitroblue tetrazolium (NBT)-reducing activity, which is an indicator of differentiation, to a level comparable to that in the case of 500 mM dbcAMP treatment. In contrast, HUFA-lyso PE (a monoacyl form) did not exert an enhancing effect on dbcAMP-induced differentiation. The enhancing effect of HUFA-PE was suppressed by a protein kinase C inhibitor, staurosporine, while a protein kinase A inhibitor, H-8, did not suppress the enhancing effect. These findings suggest that HUFA-PE might enhance dbcAMP-induced differentiation through modulation of the protein kinase C signaling pathway in HL-60 cells.

Animals↗

PubMed2001

Clonal analysis of esophageal squamous cell carcinoma with intraepithelial components.

OBJECTIVE: In tumors of the upper aerodigestive tract, field carcinogenesis is a prevailing concept which suggests that such tumors are commonly of multiclonal origin. METHODS: To test this possibility, we applied a PCR-based clonality assay utilizing the polymorphic locus of the human androgen receptor gene (HUMARA) in female patients with esophageal squamous cell carcinomas (SCCs). DNA was extracted from small pieces of tissues microdissected from multiple points of intraepithelial and invasive parts of each tumor and the adjacent epithelia in 12 cases. The HUMARA locus was PCR amplified with or without prior digestion with Hpa II. PCR products were analyzed by a genetic analyzer and polyacrylamide gel electrophoresis followed by silver staining. RESULTS: In each of 8 informative cases, the pattern of X chromosome inactivation of the major cell population in each sample was common among the samples from the invasive part and among those samples, if any, from the intraepithelial part, and was concordant between the intraepithelial and invasive parts in 5 cases and discordant in 1 case. Out of the samples of adjacent epithelia, a monoclonal pattern was demonstrated in 8 basal cell hyperplasias and 3 dysplasias, of which 2 and 1, respectively, showed inactivation patterns discordant with those of the concomitant cancers. CONCLUSION: Esophageal SCCs may often be preceded or accompanied by multiclonal precancerous lesions, and may develop through the outgrowth of single or less commonly multiple dominant clones.

Aged↗

PubMed2001

Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol.

Repetitive administration of propranolol (PL) in rats decreases the activities of cytochrome P450 (CYP) 2D enzyme(s) in hepatic microsomes. We examined the properties of 4-hydroxypropranolol (4-OH-PL) as an inactivator of rat liver microsomal CYP2D enzyme(s) using bunitrolol (BTL) 4-hydroxylation and PL 5- and 7-hydroxylations as indices of CYP2D enzyme activity. Rat microsomal BTL 4-hydroxylase activity was inhibited by the addition of 4-OH-PL to the incubation medium. The inhibition was greater after preincubation of microsomes with 4-OH-PL in the presence of NADPH than in its absence. The type of inhibition kinetics of BTL 4-hydroxylase by 4-OH-PL was changed from a competitive type to a noncompetitive type by the preincubation. The inhibition of rat liver microsomal PL 5- and 7-hydroxylases by 4-OH-PL was blocked efficiently by co-incubation with quinine, a typical inhibitor of rat CYP2D enzyme(s), or to a lesser extent by BTL. However, quinidine, a diastereomer of quinine, did not significantly protect against the enzyme inactivation. The protective capacities of the substrate and inhibitors reflected their affinities for rat CYP2D enzyme(s). BTL hydroxylase was not affected by either 1,4-naphthoquinone or 1,4-dihydroxynaphthalene which are possible metabolites of 4-OH-PL. These results provide further evidence to support the notion that PL is biotransformed by rat CYP2D enzyme(s) to 4-OH-PL, which is further oxidized to a chemically reactive metabolite in the active site. The inactivation of CYP is likely the result of covalent binding of the reactive species to an amino acid residue of the active site.

Adrenergic beta-Antagonists↗

PubMed2001

Chromosome 13 locus, Pbd2, regulates bone density in mice.

Bone density is inherited as a complex polygenic trait. Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected by bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains: SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. In this study, we report the effects of the Chr 13 QTL on peak bone density (Pbd2). First, we constructed a congenic strain P6.P2-Pbd2b, which carried a single genomic interval from the Chr 13 of SAMP2 on an SAMP6-derived osteoporotic background, to dissect this polygenic trait into single gene factors. This congenic strain had a higher bone density than the background strain using three measurement methods with different principles for bone density. Next, we measured the peak relative bone mass of the AKR/J strain and the 13 senescence-accelerated mouse (SAM) strains, which are considered to be a series of recombinant-like inbred (RI) strains derived from the AKR/J strain and other unspecified strains. We then determined the microsatellite marker haplotypes of these strains around the Pbd2 locus, in which three strains with a high relative bone mass shared the same haplotype over the 26-centimorgan (cM) region. In the Pbd2 locus, a high relative bone mass was associated with alleles of the unknown strain, whereas a low relative bone mass was associated with the alleles from the AKR/J strain. These results confirmed the existence of a Pbd2 locus regulating bone density in the SAM strains.

Alleles↗

PubMed2001

Epstein-Barr virus-associated gastric cancer in a patient with dermatomyositis.

A 59-year-old man was admitted presenting systemic rash and muscle weakness. He was diagnosed to have dermatomyositis and a check was made for internal malignancy. Gastrointestinal endoscopy revealed a Borrmann type II tumor on the middle body of the stomach. Biopsy specimens showed a well differentiated adenocarcinoma, and total gastrectomy was performed. The final diagnosis was moderately differentiated adenocarcinoma invading into the proper muscular layer, with metastases to regional lymph nodes. Most of the neoplastic cells were shown to be positive for Epstein-Barr virus by means of EBV-encoded RNA in situ hybridization. The symptoms of dermatomyositis disappeared completely after surgery.

Adenocarcinoma↗

PubMed2001

Expression of the gamma(2) chain of laminin-5 at the invasive front is associated with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

PURPOSE: Preferential expression of the gamma(2) chain of laminin-5 in invading carcinoma cells has been implicated in tumor invasion. The aim of this study was to clarify the clinicopathological and prognostic significance of laminin gamma(2) chain expression in esophageal squamous cell carcinoma (SCC). EXPERIMENTAL DESIGN: We analyzed the association between immunohistochemically detected laminin gamma(2) chain expression in esophageal SCC and clinicopathological characteristics, and we investigated whether laminin gamma(2) chain is a predictor of recurrence and/or survival. RESULTS: The cytoplasm of carcinoma cells was stained for laminin gamma(2) at levels much stronger than those in normal esophageal basement membrane. The immunoreactivities at the invasive front were often more intense than those at the superficial layer. Sections with immunostaining signals in >30% of carcinoma cells at the invasive front, which were observed in 44 of 100 cases, were judged to be positive for laminin gamma(2) chain. Laminin gamma(2) chain positivity was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis, advanced pTNM stage, recurrence, and recurrence within the first postoperative year. Patients with laminin gamma(2) chain-positive carcinoma had a significantly shorter disease-free and overall survival time than did those with laminin gamma(2) chain-negative carcinoma. Laminin gamma(2) chain retained its significant predictive value for disease-free and overall survival in multivariate analysis that included conventional clinicopathological factors. CONCLUSIONS: Our results suggest that the laminin gamma(2) chain plays a key role in the progression of esophageal carcinoma and that its detection is useful for the prediction of recurrence and poor prognosis.

Biomarkers, Tumor↗

PubMed2001

Kinetics of testosterone 6beta-hydroxylation in the reconstituted system with similar ratios of purified CYP3A4, NADPH-cytochrome p450 oxidoreductase and cytochrome B5 to human liver microsomes.

Kinetics of testosterone 6beta-hydroxylation were determined using a reconstituted system that consisted of CYP3A4, cytochrome b5 and NADPH-cytochrome P450 oxidoreductase (OR) with similar ratios as those seen in human liver microsomes and compared with those determined using human liver microsomes. Two reconstituted systems were constructed in accordance with two human liver microsomal samples that showed extremely high and low ratios of OR/CYP3A4. The Km values of testosterone 6beta-hydroxylation obtained from the reconstituted systems with high and low OR/CYP3A4 ratios were 29.3 and 35.2 microM, respectively, which were similar to that of the corresponding human liver microsomal samples (23.2 and 40.0 microM, respectively). However, Vmax values obtained from the reconstituted systems (3.7 and 0.8 pmol/min/pmol CYP3A4) were much lower than those from the human liver microsomes (44.2 and 31.1 pmol/min/pmol CYP3A4). The results suggest that the interaction between substrate and CYP3A4 in the reconstituted systems appear to be similar to human liver microsomes but that the velocity of the substrate metabolism in the reconstituted systems is different from that in human liver microsomes. In conclusion, our reconstituted systems could be used for the determination of affinity but not for the determination of the maximum velocity of substrate metabolism. Further studies on the protein-protein interactions between CYP3A4, OR, cytochrome b5 and/or a specific lipid environment are required to establish a reconstituted system showing similar kinetic properties to those of human liver microsomes.

Cytochrome P-450 CYP3A↗

PubMed2001

FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models.

UNLABELLED: Although FDG uptake is closely related to the expression of the glucose transporter (GLUT) in malignant tumors, such a relationship has not been fully investigated in inflammatory lesions. The aim of our study was to determine the expression of GLUT subtypes in experimental inflammatory lesions and to compare the results with those in malignant tumors in relation to FDG accumulation. METHODS: Rats were inoculated with a suspension of Staphylococcus aureus or allogenic hepatoma cells (KDH-8) into the left calf muscle. Five days after S. aureus inoculation (n = 9) and 14 d after KDH-8 inoculation (n = 11), [(14)C]FDG was injected intravenously and its accumulation in the infectious and tumor tissues was determined as the percentage activity of the injected dose per gram of tissue (%ID/g). The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the infectious tissues (n = 6) and the tumor tissues (n = 6). Immunohistochemical grading was assessed semiquantitatively by 5 observers. RESULTS: The [(14)C]FDG uptake was significantly higher in the tumor lesion than in the inflammatory lesion (2.04 +/- 0.38 %ID/g vs. 0.72 +/- 0.15 %ID/g; P < 0.0001). The tumor and inflammatory tissues highly expressed GLUT-1 and GLUT-3. The GLUT-1 expression level was significantly higher in the tumor tissue than in the inflammatory tissue (P < 0.05). CONCLUSION: The results based on our models showed a high FDG uptake and high GLUT-1 expression level not only in the tumor lesion but also in the inflammatory lesion. The higher GLUT-1 expression level in the tumor lesion may partially explain the higher FDG accumulation in the tumor than in the inflammatory lesion.

Animals↗

PubMed2000

Senile ocular amyloidosis in SAM and BALB/c strains of mice.

We investigated whether amyloid deposition can affect retinal atrophy in old SAMR1, SAMP1 and BALB/c mice. Immunohistochemistry revealed that old SAMP1 mice showed the deposition of the murine senile amyloid protein fibril, AApoA-II in the subconjunctival tissue, the vessel walls near the chamber angle, and the sheaths of the external ocular muscles and the conjunctival glands, but was never observed in the retina or the choroid. Although the old SAMR1 mice also showed a remarkable loss of retinal photoreceptor and ganglion cells, they never showed any amyloid deposition. The BALB/c strain did not showed any amyloid deposition either. Our data suggest that atrophy of the retina is not related to senile systemic amyloidosis in mice.

Aging↗

PubMed2000

DNA damage susceptibility and repair in correlation to calendric age and longevity.

In two mouse strains, SAM P (senescence acceleration prone) and SAM R (senescence acceleration resistant), of different longevities, with a ratio of P/R=1:2), the DNA status in the course of aging has been investigated using the DNA Alkaline Filter Elution (AFE) technique. Six different organs (brain, liver, heart, lung, intestine, and muscle) have been used in each of the four animals of a given age. Earlier it had been shown, that DNA is damaged the more the higher the age of the animal. DNA damage susceptibility, measured after exposure of organ pieces to nitroquinoline-N-oxide (NQO), is also significantly increased at higher ages, while repair, measured of NQO damaged tissue after 3 h incubation in full medium is significantly reduced. In the strain with shorter longevity the damage increments and the repair deficiencies are drastically deviating from those with higher longevity. These findings of strong coupling of the DNA status to aging as well as longevity suggest causative relations.

4-Nitroquinoline-1-oxide↗

PubMed2000

Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis.

Triple helix formation of procollagen after the assembly of three alpha-chains at the C-propeptide is a prerequisite for refined structures such as fibers and meshworks. Hsp47 is an ER-resident stress inducible glycoprotein that specifically and transiently binds to newly synthesized procollagens. However, the real function of Hsp47 in collagen biosynthesis has not been elucidated in vitro or in vivo. Here, we describe the establishment of Hsp47 knockout mice that are severely deficient in the mature, propeptide-processed form of alpha1(I) collagen and fibril structures in mesenchymal tissues. The molecular form of type IV collagen was also affected, and basement membranes were discontinuously disrupted in the homozygotes. The homozygous mice did not survive beyond 11.5 days postcoitus (dpc), and displayed abnormally orientated epithelial tissues and ruptured blood vessels. When triple helix formation of type I collagen secreted from cultured cells was monitored by protease digestion, the collagens of Hsp47+/+ and Hsp47+/- cells were resistant, but those of Hsp47-/- cells were sensitive. These results indicate for the first time that type I collagen is unable to form a rigid triple-helical structure without the assistance of molecular chaperone Hsp47, and that mice require Hsp47 for normal development.

Animals↗

PubMed2000

Genetic analysis of lifespan in hybrid progeny derived from the SAMP1 mouse strain with accelerated senescence.

The SAMP1 mouse, a senescence-accelerated mouse prone (SAMP) strain, shows accelerated senescence coupled with a short lifespan as a genetic trait, and has been used in gerontological research. The accelerated senescence and short lifespan of SAMP strains is considered to be under the control of multiple genes. To identify the chromosomal regions encompassing the genes for the accelerated senescence and short lifespan, we performed whole genome scanning with polymorphic marker loci in a progeny from a cross between the SAMP1 strain and normal B10.BR strain. A genetically recessive effect of the amyloidogenic Apoa2(c) allele from SAMP1 on chromosome 1 to shorten the lifespan was demonstrated in the progeny, consistent with the previous report. The recessive effect was observed also at D1Mit67, D5Mit267, D6Mit384 and D19Mit33, suggesting the presence of genes for accelerated senescence in the SAMP strains around these loci. Other markers on chromosomes 8, 14, 16, and 17, however, exhibited a dominant or additive effect to shorten or prolong the lifespan, demonstrating a complex genetic control of the trait.

Aging↗

PubMed2000

Age-associated DNA damage is accelerated in the senescence-accelerated mice.

We investigated how the DNA status correlates with the aging process in organisms, in different organs and in tissues using two inbred strains of mice, which are genetically related but have different senescence patterns. The SAMP1 mice belong to an accelerated senescence-prone and short lived strain, the other, SAMR1 mice are from an accelerated senescence-resistant and long lived strain. Using the alkaline filter elution technique, pieces of tissues from six organs: lung, intestine, liver, brain, muscle, and heart have been examined for DNA damage, mainly DNA single strand breaks. It was shown that in newborns the DNA damage is minimal, and it was increased significantly with calendric age in all organs in both strains. Although the correlation of DNA damage with aging differed in the different six organs, damage was significantly higher in SAMP1 mice than SAMR1 mice at later life in all organs. This is another remarkable example for the strong correlation of DNA damage and aging process, especially with senescence acceleration.

Aging↗