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Biomedical subjects

T Moriyama

Publications and source records attributed to T Moriyama.

At least 145 records · Page 8Linked to original sources

Angiotensin II stimulates interleukin-6 release from cultured mouse mesangial cells.

Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of biologic responses, including cell proliferation. Recently, IL-6 has been known to play a role in the pathogenesis of mesangial proliferative glomerulonephritis. IL-6 is now recognized as an autocrine growth factor for glomerular mesangial cells, and various inflammatory mediators have been shown to promote IL-6 release from mesangial cells. However, little is known about the noninflammatory stimuli of IL-6 release from mesangial cells. In this study, it was hypothesized that angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in cultured mouse mesangial cells (CMMC) were investigated. It was demonstrated that AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL-6 release was detected at 4 h and reached a plateau at 8 h after the addition of AngII, whereas IL-6 mRNA expression peaked at 4 h. The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor antibody abolished the enhanced DNA synthesis induced by AngII. These results raise a possibility that the growth-promoting effect of AngII on mesangial cells is at least partially mediated by IL-6 released from mesangial cells.

Angiotensin II↗

Association of angiotensin I-converting enzyme gene polymorphism with susceptibility to antiproteinuric effect of angiotensin I-converting enzyme inhibitors in patients with proteinuria.

The antiproteinuric effect of angiotensin I-converting enzyme (ACE) inhibitors in patients with renal diseases of various origins has been well recognized. However, individual responses regarding the degree of decrease in urinary protein excretion appear to vary considerably. The mechanism underlying this variable response to ACE inhibitors has not been clarified yet. A possible role of ACE gene insertion/deletion (I/D) polymorphism in the responsiveness to antiproteinuric effect of ACE inhibitors is examined. Thirty-six patients with proteinuria (23 men and 13 woman; mean age, 47 +/- 13 yr) were studied. These patients were classified into two groups on the basis of the percent decrease in their urinary protein excretion: the effective group, those with a decrease in proteinuria (18 patients, -64 +/- 19%) and the noneffective group (18 patients, +13 +/- 40%). A 287-base pair (bp) I/D polymorphism in the ACE gene was examined by polymerase chain reaction. The allelic frequencies of the ACE gene were I/D = 0.53/0.47 in the effective group and I/D = 0.81/0.19 in the noneffective group. The difference in the allelic frequencies between the two groups was significant (chi 2 = 6.25, P = 0.0114 < 0.05). Furthermore, the difference in the responsiveness of proteinuria to ACE inhibition between genotype II versus genotype ID + DD was statistically significant (chi 2 = 4.05, P = 0.0442 < 0.05). There was no significant difference between the two groups with regard to initial urinary protein level, blood pressure, renal function, and daily sodium intake. The genetic susceptibility to the antihypertensive effect of ACE inhibitors was also studied, but no significant relation was observed. This study suggests the association of ACE gene I/D polymorphism with the antiproteinuric efficacy of ACE inhibitors in patients with proteinuria.

Adult↗

Establishment and characterization of a human renal carcinoma cell line MRT-1, with special reference to the production of serine proteinase inhibitors.

A new human cell line MRT-1 was established from a metastatic lymph node of renal cell carcinoma of a 47 years old Japanese male. The cultured MRT-1 cells exhibit an epithelial appearance and contain lipid vacuoles in their cytoplasm in vitro. The modal chromosome number was 70. Doubling time and plating efficiency were 32.5 h and 5%, respectively (at the 47th passage). Injection of 1X10(6) MRT-1 cells beneath the renal capsule of nude mice resulted in tumor formation resembling the original tumor. Serine proteinase inhibitors produced by the cell line were analyzed. The cultured cells produced alpha 1-antitrypsin (alpha 1-AT) and plasminogen activator inhibitor-1 (PAl-1) into the conditioned medium. Most of the MRT-1 derived alpha 1-AT had lost the affinity to Concanavalin A when compared to the normal plasma alpha 1-AT.

Animals↗

Cytotoxic T lymphocyte responses in hepatitis C virus infection.

To clarify whether abnormal cytotoxic T lymphocyte (CTL) responses to hepatitis C virus (HCV) contribute to viral persistence and the development of subsequent chronic liver disease, we studied CTL responses of peripheral blood lymphocytes (PBLs) to HCV in patients with human leukocyte antigen (HLA) B44. CTLs were generated from PBLs by repeated stimulation with a synthetic HCV nucleoprotein peptide. The recognition of the peptide by CTLs was not strong and was restricted by an HLA B44 molecule. The minimal optimal epitope was a 9-mer peptide of HCV nucleoprotein residues 88 to 96. The CTLs also recognized an HCV antigen produced by a recombinant vaccinia virus construct. The CTLs could be induced from PBLs in 4 of 9 patients with past or ongoing HCV infection. Two of the 4 patients who demonstrated the CTL responses had cleared HCV from the circulation. In one of the 4 patients, the infecting strain of HCV was a mutant: this patient's CTLs recognized the variant peptide less efficiently than the wild-type peptide. In the remaining one patient, the amino acid sequence of serum HCV nucleoprotein residues 88 to 96 was that of a wild-type HCV but the titer of HCV RNA in serum was low. All 5 patients who did not demonstrate the CTL responses had high titers of a wild-type HCV in their serum. Thus, insufficient CTL responses to HCV and emergence of HCV variants that escape recognition by CTLs or otherwise prevent the CTL response may contribute to HCV persistence resulting in the subsequent development of chronic liver disease.

Genetic Variation↗

cDNA cloning of a cytosolic protein tyrosine phosphatase (RKPTP) from rat kidney.

A rat cDNA encoding a non-receptor type phosphotyrosine phosphatase (PTPase; EC 3.1.3.48) was identified. The 1608 bp cDNA contains a single open reading frame that predicts a 382 amino acid protein with M(r) 44,438. The predicted protein has no apparent signal or transmembrane sequences, suggesting that it is a cytosolic protein. The C-terminal region has a PTPase catalytic domain that has 40-50% nucleic acid homology to other known PTPases. The N-terminal region has little amino acid sequence homology to any other known sequences. The recombinant protein of the cloned cDNA expressed in Escherichia coli was shown to possess PTPase activity using myelin basic protein, tyrosine phosphorylated by p43v-abl tyrosine kinase, as a substrate.

Amino Acid Sequence↗

Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo.

Although CD8-positive, class I-restricted CTL play a critical role in viral clearance and immunopathology in many model systems, they have not been shown to directly kill their target cells in vivo at the single cell level. Using a hepatitis B surface Ag transgenic mouse model of class I-restricted, CTL-mediated liver disease, we now demonstrate that CD8-positive, Ld-restricted hepatitis B surface Ag-specific CTL bind and kill their target cells in vivo by triggering them to undergo degenerative cytologic changes compatible with apoptosis. Unexpectedly, the data also indicate that the pathologic consequences of this direct, Ag-specific CTL effect are much less severe than the cytodestructive, Ag-nonspecific inflammatory response that they induce when they are activated by Ag recognition.

Animals↗

Responses of inferior collicular neurons of the FM bat, Eptesicus fuscus, to pulse trains with varied pulse amplitudes.

Under free field stimulation conditions, we studied the responses of inferior collicular neurons of the FM bat, Eptesicus fuscus, to pulse trains with varied pulse amplitudes. Each pulse train consisted of 7 pulses of 4 ms delivered at 24 ms interpulse-intervals (i.e. 42 pulses/s). For a control pulse train, all pulse amplitudes were equal to a neuron's best amplitude which, when delivered in single pulses, elicited maximal number of impulses from the neuron. The amplitudes of individual pulses of the remaining pulse trains were linearly increased or decreased at a slope of 0, 14, 28, 42, 56 and 69 dB/s. All 56 inferior collicular neurons discharged to pulse trains were of two main types. Type I (N43, 77%) neurons discharged to each pulse within a train while type II (N11, 20%) neurons discharged to the first pulse of a train stimulus only. Discharge patterns of the remaining (N2, 3%) neurons changed between type I and type II when stimulated with different pulse trains. The number of impulses discharged by a neuron varied with different pulse trains. In addition, the number of impulses discharged to each pulse by type I neurons also varied among individual pulses within the train. Only 14 neurons (25%) discharged maximally to the control pulse train. Responses of the remaining neurons to other pulse trains were either 30%-120% larger than (N17, 30%) or within 30% (N25, 45%) of the control pulse train response. Furthermore, half of 56 neurons selectively discharged to a most preferred pulse train with a response magnitude which was at least 50% larger than the response to the least preferred pulse train. Possible mechanisms underlying the different discharge patterns are discussed in terms of a neuron's recovery cycle, minimum threshold and inhibitory period relative to the temporal characteristics (pulse repetition rate and amplitude) of the pulse trains.

Acoustic Stimulation↗

The effects of frequently rotating shiftwork on sleep and the family life of hospital nurses.

The effects of three frequently rotating shifts in an irregular sequence on the daily activities of 239 Japanese female hospital nurses were studied by the time-budget method. The nurses recorded their daily activities for several consecutive days. The questionnaire was returned by 80.8% of the participants, and recordings of 1016 days were analysed. A two-way analysis of variance clarified that the shift combination influenced the daily activities. The most distinct result was that nurses spent significantly more time on free-time activities on the day when they worked the night shift followed by the evening shift than they did on the day when they worked any other shift combination. Nurses offset sleep deprivation either by sleeping during the day before and after working the night shift (82-100%) or by sleeping 2 to 4 h later in the morning after working the evening shift and on days off. There was a strong positive correlation between total sleep time (including day sleep) and the length of the interval between two consecutive shifts (r = 0.95, p < 0.001). This result suggests that more than 16 h between work shifts is required to allow more than 7 h of total sleep time. In an analysis by household status, nurses who had young children (average age, 2.8 years) slept less and spent less time on free-time activities than did other nurses.

Activities of Daily Living↗

An S-alkylating reagent with positive charges as an efficient solubilizer of denatured disulfide-containing proteins.

A novel S-alkylating reagent, N-(3-bromopropyl)-N,N,N',N',N'-pentamethyl-1,3-propanedi(ammonium bromide) (TAP2-Br) which carries two positive charges in the molecule, was prepared to increase the solubility or to decrease the hydrophobicity of cysteine-containing denatured proteins (or peptides). S-Alkylation with TAP2-Br introduces two positive charges per cysteine residue, which will effectively shift the net charge of a protein in the positive direction. Disulfide-containing proteins, such as hen egg-white lysozyme, RNase A, BSA, and soybean trypsin inhibitor (Kunitz type), were reduced and S-alkylated with TAP2-Br to evaluate the potential of this reagent compared with other S-alkylating reagents such as monoiodoacetic acid, bromosuccinic acid and (3-bromopropyl)trimethylammonium bromide. The solubilities of these denatured proteins in the pH range of 2-10 indicated that S-alkylation with TAP2-Br effectively solubilized not only basic proteins (lysozyme and RNase) but also an acidic protein containing a fairly large number of cysteine residues (BSA). Moreover, the retentions of cysteine-containing tryptic peptides derived from lysozyme on reversed-phase HPLC were greatly reduced by S-alkylation with TAP2-Br. These results indicate that TAP2-Br is very useful to increase the solubility of some cysteine-containing denatured proteins and to decrease the hydrophobicity of peptides containing cysteine residue(s).

Alkylating Agents↗

The effects of daily wear of rigid gas permeable contact lenses treated with contact lens care solutions containing preservatives on the rabbit cornea.

We evaluated the effects on the rabbit cornea of daily wear of rigid gas permeable (RGP) contact lenses treated with preserved care solutions by measuring concomitant tear lactate dehydrogenase (LDH) activity followed by in vivo tandem scanning confocal microscopy (TSCM). In vivo morphologic changes were confirmed by in vitro scanning electron microscopy (SEM). Two standard commercial RGP lens wetting and soaking solutions from the same manufacturer were tested: solution A with 0.004% benzalkonium chloride (BAK) and solution B with 0.003% chlorhexidine digluconate (CHX) and 0.002% thimerosal. Two experimental PBS-based wetting and soaking solutions were also tested: solution C with 0.005% BAK and 2% hydroxypropylmethylcellulose (HPMC) and solution D with 0.005% BAK without HPMC. Instillation of solution A without contact lens wear caused significant (P < 0.01) increases in desquamation of the superficial corneal epithelium and tear LDH activity compared with control eyes. After 3 weeks of RGP contact lens daily wear (8 hours/day), modified Draize scores of ocular surface lesions on the eyes wearing RGP lenses treated with solution A increased according to the duration of lens wear. Solution B did not produce significant change. With daily wear for 4 days (8 hours/day), RGP lenses treated with solution C and solution D produced increased corneal epithelium desquamation and an increase of LDH activity in tears. These effects were greater with HPMC (solution C) than without HPMC (solution D).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.

Both PDGF and IL-1 play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis, using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.

Animals↗

Cardiovascular effects of benidipine and amlodipine in isolated tissues and anesthetized dogs.

Benidipine and amlodipine, 1,4-dihydropyridine calcium channel blocking drugs, are long-acting antihypertensive and antianginal drugs. In the present study, the vascular-selectivity and duration of action of benidipine were determined in vitro and in vivo, and compared with those of amlodipine. The relaxing effect of benidipine on the canine coronary artery precontracted by KCl (55 mM) was about 40 times that of amlodipine. The negative inotropic effect of benidipine in the electrically-stimulated canine right ventricular papillary muscle was about twice that of amlodipine. The potency ratios of the vasorelaxing effect in the coronary artery and the negative inotropic effect in papillary muscle were 1300 for benidipine and 67 for amlodipine, respectively. In anesthetized dogs, the maximum hypotensive effect and the duration of action of 3 micrograms/kg (i.v.) benidipine was almost the same as those of 500 micrograms/kg (i.v.) amlodipine. The duration of the hypotensive action of benidipine at 10 micrograms/kg (i.v.) was almost the same as that of amlodipine at 1500 micrograms/kg (i.v.). Amlodipine at 1500 micrograms/kg (i.v.) reduced mean blood pressure and left ventricular dp/dt max immediately after its administration, whereas such transient falls were not observed after the administration of benidipine at 10 micrograms/kg (i.v.). These results suggest that benidipine possesses a stronger vasodilating effect and a higher vascular-selectivity, compared with amlodipine.

Amlodipine↗

A new testicular feminization mutation found in C57BL/6J mice.

A new testicular feminization (Tfm) mutation found in the inbred strain of mice, C57BL/6JJms, was separated from the original line and established as a mutant strain. This line was named C57BL/6JJms-TfmJms. The process of discovery and breeding are described. Body weights were compared among male, normal virgin female and Tfm mice between 5 and 40 weeks of age. Tfm mice were generally intermediate in weight between male and virgin female mice. This result is different from that previously reported for the Tfm mouse strains and may be of interest in comparison between Tfm mice and their normal litter mates.

Androgen-Insensitivity Syndrome↗

[Bone mineral density of the lumbar spine and its relation to biological and lifestyle factors in middle-aged and aged Japanese women (Part 1). Relationship of age and menopause to bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry].

Bone mineral density (BMD) of the lumbar spine in 198 community-dwelling Japanese women aged 35 years and over was measured by dual-energy X-ray absorptiometry to investigate the effects of aging and menopause on BMD. A highly significant negative correlation between age and BMD was observed in postmenopausal women as widely accepted. We found a weak but statistically significant negative correlation between age and BMD in even premenopausal women, suggesting that their bone loss had commenced before menopause. Marked decrement in BMD was seen during the first ten years after menopause. Menopause clearly accelerated bone loss in the lumbar spine. Two-way analysis of variance of BMD on age and menopausal status showed that these explanatory variables had a significantly decreasing effect on BMD independently of each other. Menopausal status had a greater sum of squares than age, which suggested that menopause played a greater role in bone loss than did aging. Early menopause has been implied as one of the risk factors for bone loss. The women aged 50 to 59 having encountered menopause before 49 years old exhibited significantly lower BMD than those of similar age who experienced menopause at age 49 and older. This difference in BMD was not observed in the women aged 60 and over. Early menopause was no more likely to be a risk factor for bone loss in the elderly women. We conclude that bone loss in the lumbar spine begins before menopause and is accelerated markedly by menopause for about ten years, and that menopause has a greater decreasing effect on the bone mass than does chronological age while each of them has an independent effect on the bone mass decrement.

Absorptiometry, Photon↗

The mechanism of arachidonic acid release in collagen-activated human platelets.

The mechanism of arachidonic acid (AA) release in collagen-activated human platelets was studied. An arachidonic acid metabolite, thromboxane B2 (TXB2), was formed in parallel with the formation of phosphatidic acid (PA) without formation of lysophosphatidic acid (lysoPA) or lysophosphatidylinositol (lysoPI) in the absence of extracellular Ca2+, suggesting that AA was released from PI via a PI-specific phospholipase C (PI-PLC)/diacylglycerol (DG) lipase/monoacylglycerol (MG) lipase pathway under the cytosolic low Ca2+ concentrations. Moreover, solubilized DG lipase and MG lipase could hydrolyze the substrates at basal cytosolic free Ca2+ concentrations. Subsequently, the relationship of cytosolic free Ca2+ concentrations and formation of AA metabolites was analyzed using Ca2+ ionophore, A23187. Collagen was able to induce a release of small amounts of AA under basal cytosolic Ca2+ conditions. However, a release of large amounts of AA was induced by phospholipase A2 activated by both collagen-receptor occupancy and elevated Ca2+ levels. A TXA2 mimetic agonist, STA2 induced all the responses except for AA release. From these results, the mechanism of AA release and signal transduction in collagen-activated human platelets is discussed.

Arachidonic Acid↗

Accumulation of aluminum in cancers of the liver, stomach, duodenum and mammary glands of rats.

The aim of the present investigation was to evaluate abnormal changes in trace element concentrations during carcinogenesis. First, Al, Zn and Cu in the liver tissues of rats were measured by atomic absorption analysis over a half year of hepatocarcinogenesis. Male Wistar rats were given carcinogenic food containing 600 mg/kg of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in a basal diet for several months. After 4 to 6 months of feeding, hepatocarcinomas developed in the rats. Zn and Cu concentrations in the hepatocarcinomas of the 3'-MeDAB group significantly decreased as compared with normal liver tissues of the control groups. On the other hand, the aluminum concentration in the hepatocarcinomas was more than three times that in the normal liver tissues. The Al and Se contents of developed gastric and mammary cancers were measured in Experiment II. Male and female rats were given 1-methyl-3-nitrothoguanidine(MNNG) and 2,7-dimehtylbenz(a)anthracene(DMBA), respectively. After several months, carcinomas developed in over half of the rats. The Al and Se concentrations in cancers, livers and the blood were determined by atomic absorption analysis. It was shown that both gastric and mammary carcinomas contained a high level of aluminum and very little selenium in comparison with normal liver tissues. The present study demonstrated that aluminum accumulated in experimentally induced carcinomas in rats, i.e., cancers of the liver, stomach, duodenum and mammary glands.

9,10-Dimethyl-1,2-benzanthracene↗

[A case of multiple myeloma associated with a large subcutaneous mass in the frontal region].

A case of multiple myeloma having plasmacytoma in the frontal bone and clivus is reported. A 68-year-old female was referred to our hospital because of a subcutaneous mass in the frontal region. She was diagnosed as having multiple myeloma 7 years ago and had been treated with chemotherapy. On admission, severe anemia, hyperproteinemia and elevation of serum lambda type immunoglobulin G (IgG) were pointed out. Plain skull X-rays showed numerous punched out lesions with a large bone defect of the frontal bone. CT scan and MRI revealed a mass lesion in the clivus in addition to a large epidural tumor in the frontal region. The encapsulated frontal epidural tumor was totally resected and cranioplasty was performed with resin. Histological diagnosis was plasmacytoma of IgG lambda type. The postoperative course was uneventful, and chemotherapy was continued. There was no tumor recurrence in the frontal region and no neurological deterioration, but she died of DIC 15 months after the operation. Twenty seven cases in the literature of multiple myeloma forming cranial or intracranial plasmacytoma were briefly reviewed. Although the prognosis of such cases is poor, total resection of medullary plasmacytoma is warranted especially in multiple myeloma patients who don't have another extramedullary plasmacytoma or plasma cell leukemia.

Aged↗