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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 523 records · Page 29Linked to original sources
PubMed1997

Earthquake-induced potentiation of acute risk factors in hypertensive elderly patients: possible triggering of cardiovascular events after a major earthquake.

OBJECTIVES: We sought to investigate the potentiation of acute risk factors after the Hanshin-Awaji earthquake (7.2 on the Richter scale). BACKGROUND: The frequency of cardiovascular events increases just after a major earthquake, but the causative factors have not been fully investigated. METHODS: We studied the changes in cardiovascular risk factors in 42 elderly outpatients with well-controlled hypertension living near the epicenter (Awaji-Hokudan districts) 7 to 14 days after the earthquake when the major felt-aftershocks persisted. They all experienced the highest stress grading of 6 (catastrophic stress) according to the DSM-III-R. To study the hemostatic profile and endothelial cell state, we measured the blood pressure (BP), hematocrit and lipid profiles as well as fibrinogen, a marker of fibrin turnover (D-dimer), fibrinolytic factors (plasmin-alpha2-plasmin inhibitor complex [PIC], tissue-type plasminogen activator [t-PA] antigen and t-PA inhibitor [PAI] activity) and an endothelial cell-derived marker (von Willebrand factor [vWF]). RESULTS: Systolic and diastolic blood pressures and other variables increased after the earthquake. Before and after the earthquake, the median (25th to 75th percentiles) systolic BP was 152 (range 142 to 164) and 170 mm Hg (range 161 to 178), respectively (p < 0.0001), and the diastolic BP was 83 (range 79 to 88) and 91 mm Hg (range 84 to 96), respectively (p < 0.0001). Of blood viscosity determinants, hematocrit was 38.1% (range 40.7% to 35.9%) and 39.7% (range 42.9% to 38.3%), respectively (p < 0.001), and fibrinogen 316 (range 272 to 360) and 335 mg/dl (range 307 to 391), respectively (p < 0.05). Von Willebrand factor was 128% (range 74% to 148%) and 148% (range 100% to 178%), respectively (p < 0.01); D-dimer was 410 (range 285 to 633) and 560 ng/ml (range 391 to 888), respectively (p < 0.0001); and PIC was 0.74 (range 0.58 to 0.91) and 0.75 microg/ml (range 0.58 to 1.1), respectively (p < 0.05). In contrast, lipid profiles did not change after the quake. When the patients were classified into the high stress and moderate stress groups according to the degrees of damage to their house and injury to family members, the levels of fibrinogen, vWF, PIC and t-PA antigen were increased only in the former group, whereas BP, hematocrit and D-dimer levels were increased in both groups. These abnormalities of acute risk factors, except for vWF, were transient and decreased to prequake levels by 4 to 6 months after the quake. CONCLUSIONS: Earthquake-induced stress seems to induce transient increases in BP, blood viscosity determinants and fibrin turnover and to prolong endothelial cell stimulation. The potentiation of these acute risk factors might contribute to the occurrence of cardiovascular events just after a major earthquake in elderly subjects with hypertension.

Aged↗
PubMed1997

Differential effects of amlodipine on ambulatory blood pressure in elderly hypertensive patients with different nocturnal reductions in blood pressure.

Previous studies have discovered that amlodipine given once daily can reduce blood pressure (BP) throughout the day and night. The effects of amlodipine on day and night BP have not been fully investigated in groups of hypertensives with different diurnal variations. In a prospective study, we performed 24-h ambulatory BP monitoring before and after once-daily use of amlodipine in three groups of asymptomatic elderly hypertensive patients with different nocturnal BP reductions, as follows: 10 extreme dippers with nocturnal reduction of systolic BP > or = 20% of daytime systolic BP, 17 dippers (reduction by > or = 10% to < 20%), and 23 nondippers (reduction by < 10%). At baseline, the office and the awake BP were similar in all three groups, whereas the nighttime BP was significantly higher in the nondippers than in the dippers and in the dippers than in the extreme dippers. After treatment, the office and the daytime BP were both equally reduced in all three groups. On the other hand, the nighttime BP was significantly reduced both in the nondippers and, to a lesser extent, in the dippers. In the extreme dippers, however, no further reductions of nocturnal BP were found. Significant positive correlations were found between baseline BP levels and the BP reduction after amlodipine therapy was begun. No BP reduction > 10 mm Hg was observed when the baseline systolic/diastolic BP was < 120/70 mm Hg. Multiple linear regression analysis disclosed that the nighttime BP reduction afforded by amlodipine was dependent on the baseline nighttime BP levels, but not on the baseline nocturnal fall of BP. Once-daily use of amlodipine reduced BP levels throughout the day and night in hypertensive patients who show minimal or mild nocturnal BP fall, but it had no effects on nocturnal BP in those who show a substantial nighttime BP reduction. Thus, when we controlled using daytime office BP, amlodipine might not further reduce nocturnal BP to the extent that it accelerates the brain ischemia in some hypertensive patients with marked nocturnal BP reduction.

Aged↗
PubMed1997

Diurnal blood pressure rhythm in hypertensives with parental history of stroke.

To investigate whether the lack of nocturnal decline of blood pressure (nondipper) is a primary cause of stroke or a secondary abnormality due to stoke, we examined the relation between the blood pressure variation and parental history of stroke in 110 hypertensive patients. In nondippers (n = 54), the frequency of positive parental history of stroke was significantly higher than in dippers (n = 56) (53.7% v 33.9%, chi2 = 4.37, P = .0366). We observed a significant increase in the incidence of positive parental history of stroke in nondippers, suggesting that some genetic factors may regulate blood pressure profiles before stroke develops.

Aged↗
PubMed1997

Angiotensin converting enzyme gene polymorphism in essential hypertension based on ambulatory blood pressure monitoring.

The association of the angiotensin converting enzyme (ACE) gene polymorphism with essential hypertension is still controversial. We studied its polymorphism in 41 patients with hypertension based on ambulatory blood pressure (ABP) and 34 subjects with normal blood pressure. The ACE genotype was not significantly different between hypertensive and normotensive subjects. Casual blood pressure levels, 24 h, and daytime and nighttime ABP levels did not differ among the ACE genotype in patients with hypertension. In conclusion, the ACE genotype is not associated with essential hypertension based on ABP monitoring.

Alleles↗
PubMed1997

Specificity of polyclonal antibodies raised against a novel 24,25-dihydroxyvitamin D3-bovine serum albumin conjugant linked through the C-11alpha or C-3 position.

Novel hapten-carrier conjugants were prepared by coupling 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3 or (24R)-24,25-dihydroxyvitamin D3 [24,25(OH)2D3] 3-hemiglutarate with bovine serum albumin (BSA), to obtain an antibody with high specificity and affinity for use in 24,25(OH)2D3 immunoassay. The polyclonal antibodies showing high titre were each elicited in three or four rabbits against these two conjugants; the antibodies obtained from the former and the latter conjugants were expressed as Ab11 and Ab3, respectively. These had a much higher affinity for 24,25(OH)2D3 than that of the vitamin D binding protein (DBP). Specificity of the antibodies was investigated by crossreactivities with 11 related compounds in a radioimmunoassay (RIA) system. The Abll well discriminated the 1 alpha-hydroxylated metabolites such as 1,24,25(OH)3D3 (< or = 0.69%) and 1,25(OH)2D3 (< or = 0.25%), but significantly crossreacted with some side chain modified compounds such as (24S)-24,25-dihydroxyvitamin D3 [24S,25(OH)2D3] (> or = 67%), 25(OH)D3 (> or = 14%) and 25,26(OH)2D3 (> or = 23%). On the other hand, the Ab3 showed only negligible crossreactivities with the compounds having a different side chain structure such as 24S,25(OH)2D3 (< or = 3.0%), 25(OH)D3 (< 0.3%) and 25,26(OH)2D3 (< or = 0.53%). A significant crossreaction was found only with 1,24,25(OH)3D3 (> or = 68%). These results demonstrated that the Ab3 are promising for developing an immunoassay system which is much more specific and sensitive than conventional competitive protein binding assays based on DBP.

24,25-Dihydroxyvitamin D 3↗
PubMed1997

Biologically active oligodeoxyribonucleotides--IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3'- and 5'-end-modification.

We have determined that hexadeoxyribonucleotides (5'TGGGAG3'), with modified aromatic groups such as a trityl group at the 5'-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end had the most potent activity and the least cytotoxicity. When the 3'-end of the 5'-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3'-end, anti-HIV-1 activity increased. Moreover, among various 3'- and 5'-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5'-end and a 2-hydroxyethylphosphate group at the 3'-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity.

Animals↗
PubMed1997

Comparison of amyloid deposition in two lines of transgenic mouse that model familial amyloidotic polyneuropathy, type I.

We previously produced a transgenic mouse line designated MT-hMet30 by introducing the human mutant transthyretin (TTR) gene carrying the mouse metallothionein promoter, and showed that the presence of human variant TTR is sufficient for amyloid deposition in various tissues of these transgenic mice. However, the expression pattern of human mutant transthyretin gene in the mouse was different from that in man. To analyse pathologic processes, it is essential to establish a transgenic mouse line in which the development and tissue-specific expression of the human mutant TTR gene is the same as in man. Thus, we produced two additional transgenic mouse lines carrying the human mutant TTR gene containing either 0.6 kb (0.6-hMet30) or 6.0 kb (6.0- hMet30) of the upstream region. The expression levels of 6.0-hMet 30 gene in the liver and serum were the same as in man and about 10 times higher than those of 0.6-hMet30 gene in the liver and serum were the same as similar tissues to human patients except for the peripheral and autonomic nervous tissues. The amyloid deposition started earlier and was more extensive in 6.0-hMet30 than 0.6-hMet30 mice, suggesting that the serum levels of human mutant TTR are correlated with the occurrence and degree of amyloid deposition, to some extent. Neither amyloid deposition nor degenerative changes were observed in the peripheral and autonomic nervous systems despite the transgene expression in the choroid plexus of the 6.0-hMet30 mice. In the 6.0-hMet30 mice, amyloid deposition started at 9 months of age, although the serum level of human mutant TTR reached the adult level at 1 month. These results suggest that intrinsic environmental factors other than the mutant gene are involved in the late-onset deposition of amyloid fibrils. Transgenic mice described here should be useful for analysing such factors.

Age Factors↗
PubMed1997

Activation of human monocytes for enhanced production of interleukin 8 during transendothelial migration in vitro.

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synergistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1 beta. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-alpha, IL-1 beta, or tumor necrosis factor alpha, while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.

Antibodies, Monoclonal↗
PubMed1997

Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist.

1. The analgesic activity of CP-101,606, an NR2B subunit-selective N-methyl-D-aspartate (NMDA) receptor antagonist, was examined in carrageenan-induced hyperalgesia, capsaicin- and 4beta-phorbol-12-myristate-13-acetate (PMA)-induced nociceptive tests in the rat. 2. CP-101,606 30 mg kg(-1), s.c., at 0.5 and 2.5 h after carrageenan challenge suppressed mechanical hyperalgesia without any apparant alternations in motor coordination or behaviour in the rat. 3. CP-101,606 also inhibited capsaicin- and PMA-induced nociceptive responses (licking behaviour) with ED50 values of 7.5 and 5.7 mg kg(-1), s.c., respectively. 4. These results suggest that inhibition of the NR2B subunit of the NMDA receptor is effective in vivo at modulating nociception and hyperalgesia responses without causing the behavioural side effects often observed with currently available NMDA receptor antagonists.

Analgesics, Non-Narcotic↗
PubMed1997

Identification of a phosphodiester hexanucleotide that inhibits HIV-1 infection in vitro on covalent linkage of its 5'-end with a dimethoxytrityl residue.

It has been shown in previous reports that a guanine-rich phosphodiester oligonucleotide bearing a dimethoxytrityl (DmTr) residue on its 5'-terminal. DmTr-TGGGAGGTGGGTCTG (SA-1042), is an inhibitor of HIV-1 infection in vitro. SA-1042 interfered with the attachment of gp120 to the CD4 receptor and the subsequent entry stage of viral infection. We investigated the structure-activity relationship of the DmTr-conjugated oligomer by using 15-mer oligonucleotides with various nucleotide sequences. Results show that location of guanine nucleosides at the 5'-terminal and modification of the 5'-terminal with DmTr are essential for anti-HIV-1 activity. First, substitution of the guanine nucleoside close to the 5'-terminal of SA-1042 with another nucleotide prevented antiviral activity. Second, the existence of at least three consecutive guanine nucleosides adjacent to the 5'-terminal was required for the activity. Finally, modification of the 5'-terminal was essential for the activity. Based on these findings, the hexanucleotide, DmTr-TGGGAG, was identified as a potent inhibitor of HIV-1 infection. The hexamer was found to be capable of inhibiting the binding of gp120 to its receptor CD4 molecule, and it was also capable of inhibiting accessibility of anti-V3 monoclonal antibody to its ligand V3 peptide.

Anti-HIV Agents↗
PubMed1997

Studies on neurosteroids. V: Separation and characterization of pregnenolone 3-stearate in rat brains using high-performance liquid chromatography.

The separation and characterization of pregnenolone 3-stearate in rat brains are carried out using high-performance liquid chromatography (HPLC). The pregnenolone 3-stearate is obtained from a whole rat brain by extraction with ethyl acetate followed by silica gel column chromatography. The obtained fraction is derivatized with 1-dimethylaminonaphthalene-5-sulfonylhydrazine (dansylhydrazine) or 4-(N,N-dimethylaminosulfonyl)-7-hydrazino- 2,1,3-benzoxadiazole, and the derivative is separated by successive preparative HPLC with fluorescence detection. The chromatographic behaviors of both derivatives are identical to those of authentic samples. The former derivative obtained from the rat brain shows satisfactory mass spectral data, and after hydrolysis, dansylpregnenolone is confirmed by HPLC.

Animals↗
PubMed1997

Intrahepatic cholangiocarcinoma presenting intrabile duct extension: clinicopathologic study of five resected cases.

Intrahepatic cholangiocarcinoma, which is ordinarily a very invasive tumor and often takes a rapid and fatal course, sometimes shows macroscopic intrabile duct extension. The purpose of this study is to illustrate the clinicopathologic features of this variant of intrahepatic cholangiocarcinoma, which has occasionally been reported. Five cases of the tumor with gross extension to the bile duct lumen were studied to determine their clinical and pathologic features. The tumor showed intrabile duct growth and superficial mucosal spread in two patients. In two other patients, an apparent mass lesion accompanied the intraluminal component. In the remaining patient, a polypoid tumor infiltrated the portal tract of the left lateral segment, where it had arisen. Microscopic examination did not reveal any vascular involvement or intrahepatic or lymph node metastasis. All of the patients are alive without recurrence, except for Patient 1 who died 7 years and 7 months after surgery from a rapidly growing tumor in the liver remnant. Intrabile duct growth of intrahepatic cholangiocarcinoma may reflect indolent biological behavior and thus warrants an aggressive surgical approach, which appears to give a good prognosis.

Adenocarcinoma↗
PubMed1997

Retroperitoneal schwannoma mimicking hepatic tumor in the caudate lobe.

We report a 41-year-old woman with a retroperitoneal schwannoma mimicking hepatic tumor in the caudate lobe. Dynamic computed tomography in the early phase showed an enhanced tumor (2.7 cm in diameter) in the Spiegel lobe of the liver, which compressed the inferior vena cava (IVC). We also performed left hepatic angiographic computed tomography, and found that the tumor was less enhanced. The patient underwent laparotomy under a preoperative diagnosis of primary hepatic caudate tumor with faint neovascularity. At surgery, the tumor was found to be located between the left caudate lobe and the IVC, and was resected as being of a retroperitoneal origin. This case illustrates that tumor location must be determined with great care when the mass seems to exist at the dorsal edge of the liver, and especially when the tumor is hypovascular.

Adult↗
PubMed1997

A survey of genes expressed in mouse embryonal carcinoma F9 cells: characterization of expressed sequence tags matching no known genes.

We prepared 2,132 expressed sequence tags (ESTs) from undifferentiated mouse embryonal carcinoma F9 cells and found that 1,416 match known gene and/or protein sequences [Nishiguchi et al. (1996) J. Biochem. 119, 749-767]. To obtain information on the functions of the remaining 716 unidentified ESTs and to develop a system for characterizing ESTs matching no known genes, we analyzed their sequences by (i) repeated database searches, using the BLASTN, BLASTX, TBLASTX, and FASTA programs, (ii) using computer programs developed or modified for this work, such as the WFASTA, ORFTRNS, and MFASTA programs, together with the DBPROSITE and GRAIL programs, and (iii) examining the expression patterns of the corresponding mRNAs in F9 cells and several organs of adult mice, using the digoxigenin-labeled dot-blot method. We found that 216 of the 716 ESTs match known gene and/or protein sequences, and 307 show significant similarities to these sequences, with a Poisson p-value < 0.01. The strategy and usefulness of such analysis for characterizing unidentified ESTs are discussed.

Animals↗
PubMed1997

Nucleotide sequences of genes coding for photosynthetic reaction centers and light-harvesting proteins of Acidiphilium rubrum and related aerobic acidophilic bacteria.

The nucleotide sequences of the puf operons of the Zn-bacteriochlorophyll a (Zn-BChl a)-containing photosynthetic aerobic bacteria, Acidiphilium rubrum and Acidiphilium angustum, were determined. The nucleotide sequences of the pufL and -M of Acidiphilium cryptum, Acidiphilium multivorum, and Acidiphilium organovorum were also determined. The puf operons of A. rubrum and A. angustum contained pufB, -A, -L, -M, and -C as seen in other purple bacteria with an unknown gene directly upstream of pufB. Comparing the deduced amino acid sequences of the puf genes of the Acidiphilium species with those of other purple bacteria showed that His L168, which is highly conserved in other bacteria, is replaced by a glutamic acid in the Acidiphilium species. The three-dimensional structures of the reaction centers of Blastochloris (Rhodopseudomonas) viridis and Rhodobacter sphaeroides suggest that this residue locates closely to a special pair of bacteriochlorophylls and may be involved in the stabilization and function of "Zn-BChl a". The relative content of charged amino acid residues in the L and M subunit is a little lower in A. rubrum (10% of total) than in B. viridis (12%), and the tendency is more pronounced in the cytochrome subunit: 12.5% in A. rubrum and 18.8% in B. viridis.

Amino Acid Sequence↗