Biomedical subjects

M Hosokawa

Publications and source records attributed to M Hosokawa.

At least 145 records · Page 8Linked to original sources

PubMed1998

A comparative study of nucleolar organizer region, proliferating cell nuclear antigen and epidermal growth factor receptor staining in colon tumours.

Several studies have reported that proliferating cell nuclear antigen (PCNA), nucleolar organizer regions (NOR) and epidermal growth factor receptor (EGF-R) are cellular proliferation parameters in malignant tumours. However, the correlation of EGF-R with PCNA and NOR has not been reported in colon tumours. To clarify this, we investigated the correlation of the expression of EGF-R with PCNA and NOR in colonic epithelial tumours. Using immunohistochemical staining and one-step silver staining techniques, the expressions of EGF-R-, PCNA- and NOR-associated protein were studied in paraffin sections from five normal mucosae, 10 adenomas with mild atypia, 16 adenomas with moderate atypia, 32 adenomas with severe atypia including carcinoma in situ and 47 with invasive colon carcinomas. Significant differences were found among the respective degrees of atypia in Ag-NOR counts, PCNA labelling index (LI), and the expression of EGF-R. However, there were no significant differences among the Ag-NOR counts of the severe atypia and invasive carcinoma. There was a significant positive correlation between Ag-NOR counts and PCNA LI (P < 0.001). The Ag-NOR counts and PCNA LI in EGF-R-positive cases were higher than in EGF-R-negative cases (P < 0.001). These results indicate that each of the parameters increased significantly with the increase in atypia and the progression of cancer. Epidermal growth factor receptor provokes an exacerbation of protein synthesis and the cell cycle in colonic epithelial tumours.

Adenoma↗

PubMed1998

The mammalian carboxylesterases: from molecules to functions.

Multiple carboxylesterases (EC 3.1.1.1) play an important role in the hydrolytic biotransformation of a vast number of structurally diverse drugs. These enzymes are major determinants of the pharmacokinetic behavior of most therapeutic agents containing ester or amide bonds. Carboxylesterase activity can be influenced by interactions of a variety of compounds either directly or at the level of enzyme regulation. Since a significant number of drugs are metabolized by carboxylesterase, altering the activity of this enzyme class has important clinical implications. Drug elimination decreases and the incidence of drug-drug interactions increases when two or more drugs compete for hydrolysis by the same carboxylesterase isozyme. Exposure to environmental pollutants or to lipophilic drugs can result in induction of carboxylesterase activity. Therefore, the use of drugs known to increase the microsomal expression of a particular carboxylesterase, and thus to increase associated drug hydrolysis capacity in humans, requires caution. Mammalian carboxylesterases represent a multigene family, the products of which are localized in the endoplasmic reticulum of many tissues. A comparison of the nucleotide and amino acid sequence of the mammalian carboxylesterases shows that all forms expressed in the rat can be assigned to one of three gene subfamilies with structural identities of more than 70% within each subfamily. Considerable confusion exists in the scientific community in regards to a systematic nomenclature and classification of mammalian carboxylesterase. Until recently, adequate sequence information has not been available such that valid links among the mammalian carboxylesterase gene family or evolutionary relationships could be established. However, sufficient basic data are now available to support such a novel classification system.

Animals↗

PubMed1998

Nonepisodic angioedema associated with eosinophilia: report of 4 cases and review of 33 young female patients reported in Japan.

BACKGROUND: In 1984, Gleich et al. described 4 patients with episodic angioedema associated with eosinophilia (EAE), which was characterized by recurrent episodes of angioedema and urticaria, eosinophilia, elevated serum IgM, fever, increased body weight and a benign course without involvement of the internal organs demonstrating that it was a clinical entity distinct from the hypereosinophilic syndrome. Thereafter, 37 cases of EAE have been reported in Japan, 33 cases of which, although similar, had a different evolution from classical EAE. OBJECTIVE: To describe 4 cases and review the cases of angioedema associated with eosinophilia reported in Japan. RESULTS: Four Japanese female patients had persistent angioedema mainly involving the hands and lower legs, and eosinophilia which resolved within a few months. The review of the 37 cases of EAE in the Japanese literature demonstrated that in 33 cases, there were common characteristics which differed from EAE. These included: (1) the absence of recurrent attacks; (2) the predominance of young females (20-37 years, with a mean of 26 years); (3) the localization of the angioedema to the extremities; (4) the absence of increase in the serum IgM level, and (5) the effectiveness of low-dose prednisone or even the occurrence of spontaneous remission. CONCLUSION: We propose that persistent angioedema with eosinophilia can be classified into 2 types, i.e. one being an episodic (recurrent) type as reported by Gleich and a nonepisodic type as our 4 cases and others found in the Japanese literature.

Adult↗

PubMed1998

A morphological and morphometrical study of the retina in aging SAM mice.

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retinal, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.

Aging↗

PubMed1998

Reversible and irreversible tumor progression of a weakly malignant rat mammary carcinoma cell line by in vitro exposure to epidermal growth factor.

We examined the effects of epidermal growth factor (EGF) on tumor progression of a weakly malignant rat mammary carcinoma cell line, ER-1. In vitro treatment with EGF enhanced tumorigenicity, metastatic capacity and in vitro invasive capacity of ER-1 cells. The increased malignancy of ER-1 cells was reversible, when the cells were pretreated with EGF for 24 h, whereas it was irreversible when pretreated with EGF for 1 month. EGF treatment elevated the intracellular peroxide level in ER-1 cells. When ER-1 cells were treated with EGF in the presence of N-acetylcysteine, a chemical antioxidant, the reversible or irreversible EGF-induced progression was inhibited. These results suggest that the reversible or irreversible tumor progression in ER-1 cells occur in accordance with the duration of exposure to EGF, and that reactive oxygen species may be involved in the progression.

Acetylcysteine↗

PubMed1998

Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers.

Matrilysin is one of matrix metalloproteinases, which is supposed to have a specific role in tumor progression. Expression of matrilysin was investigated in gastric and esophageal cancers by an immunohistochemical examination. Matrilysin was expressed in all esophageal squamous cell carcinomas (13/13) and in the majority of gastric adenocarcinomas (31/35, 89%). The positive staining was observed in tumor cells of cancerous tissues. In gastric cancers, there were significant statistical correlations between matrilysin expression at the invasive front and nodal metastasis or advanced stage. These results suggest that overexpression of matrilysin has an important role in the progression of upper gastrointestinal cancers.

Disease Progression↗

PubMed1998

Age-related changes in blood pressure in the senescence-accelerated mouse (SAM): aged SAMP1 mice manifest hypertensive vascular disease.

Age-related changes in systolic blood pressure were assessed, using the senescence-accelerated mouse (SAM) model for aging research with strains SAMR1, SAMP1, and SAMP8. Each of the strains manifested a characteristic change in blood pressure with age. The SAMR1 strain, with normal aging, did not have chronologic changes from 2 to 27 months of age. The SAMP1 strain, with accelerated senescence, had a significant increase in blood pressure with age, and some (8 of 39) mice manifested hypertensive vascular disease characterized by high blood pressure, cardiac hypertrophy, and arteriolar fibrinoid necrosis at 11 to 14 months of age. The gradual increase in blood pressure after 8 to 10 months was considered to be preceded by progressive renal changes, from glomerulonephritis to contraction of the kidney, suggesting that the high blood pressure in the SAMP1 strain was of renal origin. Blood pressure in the SAMP8 strain, with age-related deficits in learning and memory, gradually decreased after 5 to 7 months of age, and was suggested to be due to the astrogliotic changes in response to spongiform degeneration in the medulla oblongata at 11 to 14 and 15 to 18 months of age.

Aging↗

PubMed1998

Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.

Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2c). After AApoAII injection, amyloid deposition occurred rapidly and advanced in an accelerated manner, as observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high-density lipoprotein (HDL), and denatured apoA-II monomer, which have the same primary structure but without a fibril conformation, did not induce amyloidosis. No amyloid deposition was observed in mice having an amyloid-resistant apoA-II gene (Apoa2b) even 3 months after AApoAII injection. Significantly less amyloid deposition was observed in mice having both types of apoA-II genes heterozygously (Apoa2b/c). These findings suggest that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in vivo. Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in vivo; it may be useful in both elucidating the pathogenesis of amyloidosis and developing effective therapeutic modalities to treat this disease.

Aging↗

PubMed1997

Age-related decline in humoral immunity caused by the selective loss of TH cells and decline in cellular immunity caused by the impaired migration of inflammatory cells without a loss of TDTH cells in SAMP1 mice.

We investigated the cellular basis of the age-related decline in antibody (Ab) and delayed-type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) in vivo in short-lived senescence-accelerated mouse (SAM) P1. In SAMP1 mice, age-related decreases in CD4+ T cells in the peripheral blood occurred earlier than in control mice and occurred in parallel with the age-related decline in Ab and DTH responses. In addition, the involution of the thymus was faster. The injection of thymic T cells from young mice before sensitization completely restored the Ab responses in aged SAMP1 mice. These data suggest that the age-related decline in Ab response is due to the age-related early loss of helper-T (TH) cells. On the other hand, the local transfer of spleen cells from sensitized aged donors into the footpads of naive syngeneic recipients evoked strong DTH responses, demonstrating the existence of DTH-mediating T (TDTH) cells in the spleens of aged SAMP1 mice. Moreover, the local injection of naive spleen cells from young donors, together with the antigen, into the footpads caused DTH responses in sensitized aged recipients. These findings indicate that TDTH cells were induced and were able to migrate and function as effector cells in aged mice. When naive spleen cells from aged donors were injected locally into the footpad, they restored the DTH response in aged mice, but this effect did not work if the cells were injected intravenously. This demonstrates that the inflammatory cells of the aged mice were able to work at the local site, but could not migrate there. The intravenous injection of naive spleen cells from young donors restored the DTH response in aged mice, suggesting that the endothelial cells of aged mice were not impaired and permitted the inflammatory cells to migrate into the extravascular tissues. Thus, although the age-related decline of the Ab and DTH responses occur in parallel, we found different effects of aging on TH and TDTH cells in SAMP1 mice. Furthermore, our data suggest that the reason for the low DTH response in aged SAMP1 mice is not the loss of TDTH cells, but rather the impaired migration of inflammatory cells into the local site.

Aging↗

PubMed1997

Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.

Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis. We have identified and purified a more basic amyloid protein from old-mouse liver. N-terminal sequencing of the protein revealed that the pro-segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N-terminal glutamine residue of mature apoA-II protein. MS analysis revealed the deposit of intact pro-apoA-II protein (molecular mass 9319 Da). Antiserum was prepared for staining of the AApoAII amyloid deposition. The relative abundance of pro-apoA-II to mature apoA-II in the amyloid-fibril fraction isolated from livers of mice with severe amyloidosis was 14.1%. The similar abundance of pro-apoA-II in the amyloid fibril fraction from the spleen (16.3%) suggested that deposited pro-apoA-II originated from the blood. The concentration of pro-apoA-II was much lower in the serum (1.5% of mature apoA-II) than in the amyloid-fibril fraction. There was no difference in the content of pro-apoA-II between the amyloidogenetic R1.P1-Apoa2c and amyloid-resistant SAMR1 strains at the age of 3 months. The abundance of pro-apoA-II in the amyloid-fibril fraction compared with the serum suggested that it plays a key role in the initialization of mouse senile amyloidosis.

Amino Acid Sequence↗

PubMed1997

Large-scale biological monitoring in Japan.

Data from the large-scale biological monitoring program in Japan were assembled and analyzed and the following results were obtained. All workers handling lead and eight kinds of major organic solvents received physical examinations and biological monitoring at the same time. Therefore, the number of workers handling industrial chemicals and that received physical examinations and the number of workers been examined by biological monitorings were similar to each other. The total number of cases examined from 1989 to 1994 was about 661,000 for lead in the blood and about 4,173,000 for the urinary metabolites of eight organic solvents. The results were classified into three categories and category 3 consists of workers having exposure concentrations above the 1988-1989 biological exposure indices of the ACGIH with the exception of lead concentration in the blood where the limit in Japan was set at 40 micrograms/100 ml. The percentage of exposed workers in category 3 was 1.4% for blood lead and 0.2-2.4% for the urinary metabolites of the eight organic solvents. The percentage of exposed workers in category 3 for blood lead, delta-aminolevulinic acid, urinary mandelic acid, N-methylformamide and 2,5-hexanedione in the urine has decreased with time. In ambient monitoring, the percentage of workplaces in classification 3 for lead and styrene also has decreased with time.

Aminolevulinic Acid↗

PubMed1997

Melatonin suppresses hyperglycemia caused by intracerebroventricular injection of 2-deoxy-D-glucose in rats.

To elucidate the role of melatonin (MT), we examined the effects of intracranial injection of MT and an MT-antagonist (S20928) on the hyperglycemic response to intracranial injection of 2-deoxy-D-glucose (2DG) in rats. The hyperglycemic and hyperglucagonemic responses caused by intracerebroventricular injection of 2DG were inhibited by intracerebroventricular co-injection of MT, but enhanced by co-injection of the MT-antagonist. Intraperitoneal injection of MT also inhibited the hyperglycemic response, though the inhibition seemed to be less than that after intracranial injection of MT. These results suggest that MT plays an endogenously suppressive role in the hyperglycemia caused by 2DG, possibly through a brain site.

Animals↗

PubMed1997

Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II.

Mouse apolipoprotein (apo) A-II has three variants (type A, B, and C) among inbred strains. To clarify the role of ApoA-II in the metabolism of high density lipoproteins (HDL), we constructed a new congenic mouse strain (P1.R1-Apoa2b) with type B ApoA-II of the SAMR1 strain on the genetic background of the SAMP1 strain, and examined it together with another ApoA-II congenic strain (R1.P1-Apoa2c) containing type C ApoA-II of the SAMPI strain on the SAMR1 strain and the parental SAMP1 and SAMR1 strains. Genetic characterization of the congenic strains indicated that only small regions surrounding the ApoA-II gene of the parental strains had been transferred. The strains with Apoa2c had lower plasma concentrations of HDL and ApoA-II, and a smaller HDL particle size than strains with Apoa2b. We detected no significant differences in the mRNA levels of ApoA-II or in the in vitro translational efficiency of the ApoA-II mRNA among the four strains. These findings suggested that the differences in the post-translational modification or efficiency of secretion between the Apoa2b and Apoa2c protein regulates the ApoA-II concentration which in turn determines the concentration and size of HDL in mice.

Animal Feed↗

PubMed1997

Possible roles of an adult T-cell leukemia (ATL)-derived factor/thioredoxin in the drug resistance of ATL to adriamycin.

Chemotherapy for adult T-cell leukemia (ATL) has been reported to fail to induce complete remission because of drug resistance in most patients. We have examined the expression of an ATL-derived factor (ADF)/thioredoxin in relation to resistance to adriamycin (ADM) in various T-cell leukemia cell lines including ATL cell lines. Immunoblot analysis demonstrated that ATL cell lines expressed ADF/thioredoxin at levels 2.8 to 12 times those of other T-cell acute lymphocytic leukemia (T-ALL) cell lines, and that ATL cell lines were 2 to 15 times more resistant to ADM than other T-ALL cell lines. Therefore, we established ADM-resistant cell lines from three different ATL cell lines, and examined the correlation between ADM resistance and expression of ADF/thioredoxin. ADM-resistant ATL cell lines were also found to be resistant to other drugs such as cisplatin and etoposide, and they expressed ADF/thioredoxin at levels 5 to 10 times those of parent ATL cell lines. Diamide and sodium selenite, which have been reported to inhibit ADF/thioredoxin, restored the sensitivity to ADM in ATL and ADM-resistant ATL cell lines. The MDR-1 gene product, a membrane P-glycoprotein (Pgp), was not expressed on ATL cell lines or ADM-resistant ATL cell lines. Topoisomerase II and glutathione peroxidase activities in T-cell leukemia cell lines were not correlated with ADM resistance. These results suggest that ADF/thioredoxin may play an important role in the drug resistance of ATL cells to ADM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Molecular cloning and expression of cDNAs encoding rat brain and liver cytosolic long-chain acyl-CoA hydrolases.

cDNAs encoding the long-chain acyl-CoA hydrolases (ACHs) from rat brain and liver, referred to as rBACH and rLACH1, respectively, were isolated and sequenced. The rBACH cDNA contained an open reading frame encoding a 338-amino acid polypeptide with a calculated molecular weight of 37,559, of which the deduced amino acid sequence matched partial amino acid sequences directly determined for peptides generated by tryptic digestion or CNBr cleavage of purified rBACH. The rLACH1 cDNA contained an open reading frame encoding a 343-amino acid polypeptide with a molecular weight of 38,240. When expressed in Escherichia coli, these cDNAs produced palmitoyl-CoA hydrolase activity and 44-kDa proteins with molecular masses similar to those of purified rBACH and rLACH1 (43 kDa). These expressed proteins and enzyme activity were immunoblotted and neutralized, respectively, by anti-rBACH or anti-rLACH1 antibodies. rLACH1 cDNA had 84 and 94% identity with rBACH cDNA at the nucleotide and amino acid levels, respectively. However, the 5'-end of the former cDNA which contained the N-terminal coding region of rLACH1 was entirely different from the corresponding region of rBACH cDNA, suggesting that these enzymes may be generated by alternative use of exons of the same gene. Northern blot analysis showed that ACH mRNA was expressed constitutively in the rat brain and testis, whereas its expression in the liver was inducible by treatment with the peroxisome proliferator. This study demonstrated the molecular diversity of ACH and suggested the presence of tissue-specific mechanisms to regulate the ACH gene expression.

Amino Acid Sequence↗

PubMed1997

Cell death in the inner ear associated with aging is apoptosis?

Programmed cell death (apoptosis) in the inner ear of senescence-accelerated mouse was identified using specific labeling of fragmented DNA (the TUNEL method). In spite of some inter-individual differences, the apoptotic cells were predominantly found in the phylogenetically newer part of the inner ear, the cochlea and the saccules. In the saccules, sensory hair cells as well as supporting cells were positively labeled. In the cochlea, positive staining was detected in inner and outer hair cells, pillar cells, Deiters' cells, interdental cells, the stria vascularis (marginal cells, intermediate cells, basal cells), and cells in Reissner's membrane. The present results suggest that age-related cell death, which may cause hearing impairment and dysequilibrium, is due to apoptosis occurring in the inner ear.

Aging↗

PubMed1997

Inheritance and strain distribution of a persistent hyaloid vascular system in mice.

The mode of inheritance of a persistent hyaloid vascular system was investigated in an inbred strain of Senescence-Accelerated Mouse P9 (SAMP9) by conducting crosses between SAMP9 and SAMR1, a strain which shows normal regression of the hyaloid vascular system. We also examined the distribution of this abnormality in 12 inbred SAM strains and in eight commonly used inbred strains of mice. Ophthalmoscopic examination of the eyes of 5-week-old mice, which have transparent lenses, revealed the persistence of a hyaloid vascular system in only one female F1 hybrid out of 66 offspring. The observed segregation ratio of affected to unaffected mice was 25:52 in males and 37:44 in females, following the reciprocal backcross progeny between SAMP9 mice and F1 hybrids. The results of the strain distribution study indicated that 8-97% of the mice among six strains of SAM exhibited the persistence of a hyaloid vascular system, whereas the other inbred strains did not exhibit this abnormality. These observations suggest that at least two major genes may contribute to the persistence of a hyaloid vascular system, and suggest that the SAM strains comprise a group of related inbred strains.

Animals↗

PubMed1997

Restoration of macrophage tumoricidal activity by bleomycin correlates with the decreased production of transforming growth factor beta in rats bearing KDH-8 hepatoma cells.

To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon gamma (IFN gamma) mRNA expression, tumor necrosis factor alpha (TNF alpha) production, nitric oxide (NO) production and macrophage tumoricidal activities in rats bearing KDH-8 hepatoma cells, which secreted a large amount of transforming growth factor beta (TGF beta), and these processes in KDH-8 tumor-bearing rats treated with bleomycin. We found that IFN gamma mRNA expression, TNF alpha production, NO production and macrophage cytotoxic activities were lower in the KDH-8-bearing rats than in normal rats. On the other hand, low-dose bleomycin restored the macrophage cytotoxic activities, NO production, IFN gamma mRNA expression and TNF alpha production in the KDH-8-bearing rats. In vitro experiments showed that KDH-8-derived TGF beta decreased the IFN gamma mRNA expression and TNF alpha production in splenocytes, and NO production in peritoneal macrophages. These results suggest that low-dose bleomycin restored the cytokine production and macrophage tumoricidal activities in the KDH-8-bearing rats by decreasing KDH-8-derived TGF beta.

Animals↗