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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 649 records · Page 36Linked to original sources

Surgical stress and transient postoperative psychiatric disturbances in aged patients studied using the Yamaguchi University Mental Disorder Scale.

Psychiatric disturbances often occur in aged patients after surgery, but there is no easy or precise method of predicting their occurrence. We devised an easy mental test, the Yamaguchi University Mental Disorder Scale (YDS), based on the surgical perspective. Using both this new method and the Hasegawa mental disorder scale (HDS), we examined 106 patients who had undergone general anesthesia. HDS only was used in 70 cases, while 36 cases were examined by the newly devised YDS and were then compared with the findings obtained by HDS. On the HDS examination, factors affecting postoperative psychiatric disturbances were, in order of frequency: entering the ICU, amount of bleeding, and duration of surgery. Aged patients who experienced severe surgical stress had a higher risk of developing transient postoperative psychiatric disturbances. On the YDS examination, the relationship between surgical stress and transient postoperative psychiatric disturbances was clearly indicated, as was the case with HDS. Postoperative delirium was seen in a significant proportion of patients with low preoperative scores on YDS (P < 0.05), while no significant difference was observed between the mean preoperative scores on HDS and postoperative delirium. In the preoperative evaluation using YDS, postoperative delirium was found to be predictable, and YDS is thus considered to be a more valuable tool in managing aged patients.

Adult↗

Amyotrophic lateral sclerosis with hypertensive attacks: blood pressure changes in response to drug administration.

Blood pressure changes in response to intravenous drug administration were examined in a respirator-dependent 49-year-old patient with sporadic amyotrophic lateral sclerosis (ALS) who developed severe hypertensive attacks. She showed severe hypertension and tachycardia during the daytime and nocturnal hypotension without compensatory tachycardia, which were consistent with the autonomic phenomenon reported in ALS patients. Infusion of phenotolamine (2.5 mg) induced an abrupt 90 mmHg decrease in systolic pressure and slight increase in heart rate. Propranolol (1 mg) infusion induced decreases in both systolic pressure (36 mmHg) and heart rate (17 beats/min), although the pressure decrease was transient while the heart rate remained at the decreased level Infusion of diazepam (10 mg) induced a 47 mmHg decrease in systolic pressure and a 23 beats/min increase in heart rate. These vasomotor responses indicate the distinct participation of abnormally augmented sympathetic tone, and especially of alpha-sympathetic hyperactivity rather than of beta-sympathetic hyperactivity, in the hypertensive attacks occurring in this ALS patient.

Adrenergic alpha-Agonists↗

Role of endogenous substance P in ethanol-induced mucosal damage in the rat stomach.

To determine the role of endogenous substance P in ethanol-induced mucosal damage, two experiments were performed. In the first experiment, the stomachs of anesthetized rats were doubly cannulated and gastric damage was induced with 5ml of 30% ethanol in the gastric lumen. The damage was ameliorated by pretreatment with capsaicin (0.16 and 1.6 mM) and spantide (100 mg/kg, i.v.). In the second experiment, the gastric mucosa of these rats was perfused with physiological saline containing pepstatin (10 microliters/ml). Endogenous substance P (SP) in the perfusate was measured by enzyme immunoassay (EIA). The peak SP levels were increased by capsaicin (0.16-1.6 mM) in a concentration-dependent manner. Perfusion with 50% ethanol for 5 min increased the SP levels approximately threefold. Perfusion with 1.6 mM capsaicin, followed by 50% ethanol, reduced the injured area to about one-quarter of the original injured area. The peak SP levels during perfusion with 50% ethanol after pretreatment with 1.6 mM capsaicin did not differ from those observed after vehicle pretreatment (control). The area under the curve for SP release during 50% ethanol perfusion after vehicle perfusion was not reduced by previous perfusion with 1.6 mM capsaicin followed by 50% ethanol, indicating that the prevention of ethanol-induced injury by capsaicin may be due to excess amounts of different neuropeptides released simultaneously.

Animals↗

Azulene derivatives as TXA2/PGH2 receptor antagonists--II. Synthesis and biological activity of 6-mono- and 6-dihydroxylated-isopropylazulenes.

In order to examine the correlation between activity and hydrophilicity of the side chain of sodium 3-[4-(4-chlorobenzenesulfonylamino)butyl]-6-isopropylazulene -1-sulfonate (KT2-962), a non-prostanoid TXA2/PGH2 receptor antagonist, one or two hydroxyl groups were introduced into the isopropyl moiety. A series of 6-hydroxylated-isopropylazulenes were synthesized by regioselective oxidation of 6-isopropylazulenes and their in vitro and in vivo antagonistic activities were studied. Both the primary and tertiary alcohols, monohydroxylated derivatives, exhibited potent biological activities comparable to unmodified 6-isopropylazulenes both in vitro and in vivo. In contrast, the activities of 1,2- and 1,3-diols of 6-substituted derivatives, markedly decreased, but recovered by O-isopropylidenation of the dihydroxyl moiety. These findings indicate that the moderate hydrophobicity of substituent at the 6-position of the azulene ring might be required for the activity and the size of the substituent at this position, not so rigid for keeping potent biological activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Relationship between QRS duration and repolarization abnormalities in patients with Wolff-Parkinson-White syndrome.

Marked T wave abnormalities in 12-lead electrocardiograms often appear after radiofrequency ablation in patients with Wolff-Parkinson-White (WPW) syndrome. Durations of the QRS complex before ablation have been reported to be significantly greater in patients with repolarization abnormalities after ablation than in those with normal repolarization. However, there has been no report concerning the relationship between QRS duration and repolarization abnormalities before ablation. It has been reported that QRST isointegral maps are dependent on local cellular repolarization properties but largely independent of activation sequence, and that they provide quantitative information about repolarization abnormalities. Isointegral maps were constructed from data recorded in 34 patients with WPW syndrome and QRS durations of 0.1 second or longer (21 patients with left-sided accessory pathways and 13 with right-sided pathways) in order to investigate the relationship between QRS duration and abnormalities in repolarization properties during preexcitation. Body surface ECGs were recorded with an 87-lead system at a sampling interval of 1 ms. The QRST values (mean +/- 2SD) from 607 normal individuals were taken to represent the normal range. The area with abnormally low QRST values was designated as the -2SD area and the sum of the QRST values (sigma QRST) in this area was calculated. The QRS duration was found to be significantly related to sigma QRST. These results demonstrate that the patients with WPW syndrome had abnormalities in local repolarization properties that were significantly related to QRS duration during preexcitation. The degree of preexcitation may be important in producing these abnormalities in patients with manifest WPW syndrome. This may result in T wave abnormalities after ablation of the accessory pathway attributable to cardiac memory.

Adolescent↗

Relationship between infrared spectra and isomorphous substitution in smectites: a computer simulation study.

Smectites, members of the 2:1 layer silicate family, share the common feature that two tetrahedral sheets sandwich a sheet of octahedrally coordinated metal ion. The diversity of the members of the 2:1 layer silicates occurs because of their capacity for isomorphous substitution of various cations in the octahedral or tetrahedral sheets. Substitution of a divalent metal ion (such as Mg2+) for the trivalent Al3+ or a trivalent metal ion (such as Al3+) for the tetravalent silicon results in a net negative charge, which then undergoes interaction with positive ions (the exchangeable cations) to form an interlayer hydrated phase. Local density functional (LDF) calculations were employed to model isomorphous substitution of Al3+ by Na+, K+, Mg2+, Fe2+, and Fe3+ in the octahedral layer of a dioctahedral smectite clay such as montmorillonite. The energies of the isomorphous substitution were then compared with the experimental observation. The ordering for successful substitution is Al3+ > Fe3+ > Mg2+ > Fe2+ > Na+ < K+. This ordering is consistent with experimental observation. The vibrational frequencies for the isomorphous substituted systems were calculated by LDF calculation and were compared with the experimental IR results. The results match very well with experiment. This understanding will help in successful prediction of the catalytic activity of smectite clays.

Aluminum Silicates↗

Capsular capture of silicone intraocular lenses.

PURPOSE: To examine the incidence of capsular capture in silicone IOL implantation and determine its effect on visual acuity. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: This study comprised 144 eyes that had phacoemulsification with three-piece silicone intraocular lens (IOL) implantation that were evaluated about 3 months after surgery. The examination included the status of the haptic and optic placement, extent of posterior capsular opacification (PCO), and the best corrected visual acuity. RESULTS: One hundred twenty-eight eyes had an in-in haptic placement, 15 had in-out placement, and 1 had out-out placement. Capsular capture occurred in 30 eyes (20.8%). The extent of PCO in eyes with capsular capture was greater than in those without capture. The best corrected visual acuity in eyes with capsular capture was worse than in those without capture. In addition, eyes with in-out and out-out haptic placement had significantly worse PCO and visual impairment than the eyes with in-in placement. CONCLUSION: There was a high incidence of capsular capture after silicone IOL implantation. This complication, along with the undesirable placement of the haptics, led to PCO and thus visual impairment.

Humans↗

Risk factors for corneal endothelial injury during phacoemulsification.

PURPOSE: To determine the principal risk factors for corneal endothelial injury during phacoemulsification. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: We prospectively investigated 859 consecutive eyes of 800 patients who had had phacoemulsification surgery. The percentage of corneal endothelial cell loss at 3 months after surgery was quantitated using specular microscopy. The firmness of the nucleus was graded by Emery's classification prior to surgery. We selected nine variables that could be associated with endothelial injury. The univariate associations between the endothelial cell loss and these variables were evaluated using simple correlation coefficients. A multiple linear regression analysis was performed to identify independent predictors of endothelial cell loss. RESULTS: In the simple regression analysis, older age, small pupil diameter, high nucleus grade, large nucleus, greater infusion volume, type of IOL implanted, and a greater amount of total emitted ultrasound energy were univariately associated with endothelial cell loss. In the multiple linear regression analysis, the best final model (R2 = 0.42) identified high nucleus grade, greater infusion volume, type of IOL implanted, and large nucleus as independent predictors of endothelial cell loss. CONCLUSION: Both univariate and multivariate analyses identified the firmness of the nucleus as the most significant risk factor for endothelial cell loss. Therefore, mechanical contact with nuclear fragments is considered the principal cause of endothelial injury.

Adult↗

Long-term engraftment of precultured post-5-fluorouracil allogeneic marrow in mice conditioned with a nonmyeloablative regimen: relevance for a gene therapy approach to tolerance induction.

Introduction of MHC class I Kb cDNA via recombinant retrovirus into B10.AKM (Kk) bone marrow cells (BMC) has been shown to confer specific hyporesponsiveness to B10.MBR (Kb) allogeneic skin grafts in lethally irradiated B10.AKM recipients of the transduced syngeneic BMC. We have recently developed a nonmyeloablative conditioning regimen that allows engraftment of fully MHC-mismatched allogeneic bone marrow and the induction of donor-specific tolerance. We ultimately plan to adapt this nonmyeloablative regimen for the use of retroviral transfer of the Kb gene to syngeneic marrow. As a step toward this goal, we have assessed the effects of our current BMC transduction protocol on engraftment of class I mismatched marrow in mice prepared using the nonmyeloablative regimen. BMC from B10.MBR (KbIkDq) mice treated 2 days earlier with 5-fluorouracil (5-FU) were cultured for 4 days with rIL-3 and rIL-6, and then injected into B10.AKM (KkIkDq) recipients conditioned with anti-CD4 and anti-CD8 mAbs, 7 Gy of thymic irradiation and 3 Gy of whole body irradiation. Engraftment was comparable to that of freshly prepared normal B10.MBR marrow. All recipients of 10(6) precultured BMC developed long-term multilineage mixed WBC (white blood cells) chimerism, and six of seven of these animals showed long-term specific tolerance to B10.MBR skin grafts. Four of seven recipients of 2 x 10(5) precultured BMC showed long-term repopulation by the donor of > 1% of multiple WBC lineages and four of five recipients showed specific tolerance to B10.MBR tail skin. These data suggest that our previously described nonmyeloablative conditioning regimen could be applicable to the gene therapy approach for the induction of donor-specific transplantation tolerance.

Animals↗

In vivo ESR studies on pharmacokinetics and metabolism of parenteral lipid emulsion in living mice.

PURPOSE: We applied non-invasive and real-time method with in vivo ESR spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as a drug carrier in living mice. METHODS: A spin-labeled triglyceride (SL-TG) was newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR spectra in mice were observed after intravenous administration of the lipid emulsion. RESULTS: In vivo ESR spectra consisted of three components, coinciding with the in vitro spectra of SL-TG particles, free and immobilized fatty acids. The amount of the components depended on both the observing domain and the period after administration. In the chest, all three components were observed, while SL-TG particle was lacking in the abdomen. The half-life of the lipid particles in the chest was 2 hr. CONCLUSIONS: Non-invasive and real-time analysis of drug carriers in living animal is successfully accomplished using an in vivo ESR method.

Animals↗

HLA-DR antigen expression in colorectal carcinomas: influence of expression by IFN-gamma in situ and its association with tumour progression.

The authors attempted to investigate the host's immune response against colorectal carcinoma through the expression of HLA-DR antigen on carcinoma cells (Ca) on normal epithelia immediately adjacent to carcinoma (AN) in relation to tumour progression. The expression of HLA-DR antigen on Ca and on normal epithelia, both on AN and those 5-10 cm removed from the carcinoma (RN), were examined immunohistochemically. mRNAs of cytokines, IFN-gamma and TNF-alpha, were detected by reverse transcription-polymerase chain reaction (RT-PCR) in both carcinoma and remote normal tissues. The expression of HLA-DR antigen on AN was significantly increased compared with RN. Patients with tumours showing HLA-DR staining both in Ca and AN were in less advanced Dukes' stages (Dukes' A or B) compared with those without the stain. Furthermore, the expression of HLA-DR antigen in normal mucosa coincided significantly with the existence of IFN-gamma mRNA. Detection in carcinoma tissues of IFN-gamma mRNA that leads to the induction of HLA-DR antigen on AN could be an indicator of a host's immune response to carcinoma. These in vivo observations might be clinically applicable to the prediction of patients' immune responsiveness to carcinomas.

Adult↗

The relationship between lipoprotein(a) and low density lipoprotein receptors during the treatment of hyperthyroidism.

To determine whether the low density lipoprotein (LDL) receptor pathway is involved in the catabolism of plasma lipoprotein (a) [Lp(a)], serum lipids, Lp(a), and LDL receptor activity were measured in seven patients with hyperthyroidism before and after methimazole treatment given hyperthyroidism is associated with enhanced LDL receptor activity. LDL receptor activity in patients was estimated by the equation using the serum concentrations of apolipoprotein (apo) B and C-II. When euthyroidism was achieved after treatment, not only did serum total cholesterol, high density lipoprotein-cholesterol, apo B, and LDL-cholesterol (LDL-Ch) levels rise, but Lp(a) significantly increased and calculated LDL receptor activity significantly decreased. The changes in LDL receptor activity were significantly correlated with the changes in LDL-Ch as expected, but not with changes in Lp(a). These results suggest that the serum concentration of Lp(a) is lowered in hyperthyroidism, probably by a mechanism other than the enhanced activity of the LDL receptor, and that the LDL receptor pathway is involved in the catabolism of Lp(a) to a limited extent.

Apolipoproteins↗

Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice.

The effect of dimethylarsenics on the pulmonary tumorigenesis initiated by 4-nitroquinoline 1-oxide (4NQO) in mice was examined. The exposure of mice to dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics in mammals, resulted in not only promotion but also progression of the tumorigenic process in the lungs of mice administered 4NQO. Furthermore, dimethylarsenics influenced the differentiation process in lung tumorigenesis by 4NQO. These results may pave the way for the elucidation of lung carcinogenesis caused by arsenics.

4-Nitroquinoline-1-oxide↗

Effects of aging on the regulation of intracellular pH in the rat jejunum.

Jejunal villus cells from young-adult (6 months) and senescent (24 months) male Wistar rats were studied to evaluate the effect of aging on intracellular pH (pHi) regulation. pHi was measured by quantitative fluorescence microscopy by using BCECF-AM [2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein acetoxy methylester] under basal conditions and after inducing cytoplasmic acidification with pulsed NH4Cl. In the senescent rats, the recovery rate from the acidified levels was significantly lower than that in the young-adult rats (.208 +/- .005 vs .255 +/- .004 pH units/min). The relationship between pHi recovery and external Na+ concentration followed Michaelis-Menten type kinetics, the maximum velocity (Vmax) of alkalinization being significantly lower in the senescent rats than in the young-adult rats (.227 +/- .033 vs .297 +/- .024 pH units/min). These results indicate that the recovery of pHi from an acidic level was slower in the senescent rats, due to the reduced activity of Na+/H+ exchange as revealed by the decreased Vmax value.

Aging↗

Functionally important residues of aromatic L-amino acid decarboxylase probed by sequence alignment and site-directed mutagenesis.

To identify functional residues of rat liver L-aromatic amino acid decarboxylase (AADC), we aligned the sequences of 13 group II amino acid decarboxylases and performed mutational analysis on the residues that were invariant or conservatively substituted. Replacements of His192, Asp252, Asp271, Ser296, Lys303, Tyr332, and Arg355 with alanine residues decreased the AADC activity (kcat/K(m)) by more than 10(4)-fold. Conservative replacements of [Asp252-->Glu], [Lys303-->Arg], and [Tyr332-->Phe] also resulted in decreases in activity by more than 10(4)-fold, indicating that both the chemical properties and the shape of these residues are essential for catalysis. The presence of a Schiff base between the amino group of Lys303 and the coenzyme pyridoxal 5'-phosphate is important for catalysis, probably at the transaldimination step. The enzyme activity was essentially unaffected by conservative mutation of [Arg355-->Lys], showing that the presence of a basic group at position 355 is necessary and sufficient for the catalysis. Replacement of [Thr246-->Ala], [His269-->Ala], and [Trp363-->Leu] yielded mutant enzymes that were 1-8% as active as the wild-type enzyme; these residues are not essential for the catalysis but are considered to contribute to the activity through conformational or other effects. The roles of the catalytically important residues of the group II amino acid decarboxylases probed in this study were discussed in the light of their relationship with the residues of other pyridoxal enzymes.

Amino Acid Sequence↗

Identification of a novel growth-promoting factor with a wide target cell spectrum from various tumor cells as catalase.

We have previously reported the purification from human erythrocyte extracts of a novel growth-promoting factor with a wide target cell spectrum. The factor has been identified as catalase. As cell extracts from a variety of tumor cell types exhibited both growth-promoting and catalase activities, the relationship between the two activities was examined using cell extracts from three different cell types, human myeloid cells (U937), human melanoma cells (A375-C6), and human B cells (Daudi). The growth-promoting and catalase activities were well correlated in these cell extracts. The antibody against human catalase absorbed not only catalase activity, but also the growth-promoting activity of extracts from these cell types. Treatment of the cell extracts from these cells with an irreversible catalase inhibitor, aminotriazole, abolished both the catalase and growth-promoting activities. In contrast, glutathione peroxidase (GSH-Px) activity was neither absorbed with the anti-catalase antibody, nor inhibited by aminotriazole. In addition, GSH-Px exhibited growth-promoting activity only in the presence of glutathione (GSH). These results, in conjunction with the effect of aminotriazole on the growth-promoting activity of catalase, suggest that catalase is the major growth-promoting molecule in the cell extracts, and H2O2-decomposing activity is important. Northern blot analysis revealed that these cells contained authentic catalase mRNA, and the mRNA level was compatible with the catalase and growth-promoting activities in the cell extracts. These results suggest that the growth-promoting activity in the tumor cell extracts is due to catalase.

Amitrole↗

Atypical adenomatous hyperplasia and bronchoalveolar lung carcinoma. Analysis by morphometry and the expressions of p53 and carcinoembryonic antigen.

Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor of bronchoalveolar carcinoma (BAC). To define the steps in its development and to clarify at which stage critical cellular events occur, we studied 65 lesions of AAH, early BAC, and overt BAC by morphometric analysis and immunohistochemical evaluation of expression of p53 protein and carcinoembryonic antigen (CEA). Both the nuclear area and lesion size increased from AAH to early BAC and to overt BAC; the standardized variation of nuclear area was smallest in overt BAC. Discriminant analysis using these morphometric parameters revealed high accuracy rates for the respective categories. Analysis of distribution of lung lesions in terms of nuclear area and lesion size yielded effective, potentially diagnostic cutoff values for distinction between AAH and early BAC. Both p53 and CEA expression tended to increase with the advance of atypia grade. In particular, high-level p53 expression was strongly correlated with overt BAC. These findings indicate that our classification of lung lesions is reproducible and thus useful for analyzing the development of BAC. Furthermore, some kinds of p53 gene abnormalities that are correlated with high-level p53 expression likely play an important role in the progression of early to overt BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗