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Biomedical subjects

M Doi

Publications and source records attributed to M Doi.

At least 109 records · Page 6Linked to original sources

Multiple regression analysis for assessing the growth of small hepatocellular carcinoma: the MIB-1 labeling index is the most effective parameter.

The aim of this study was to clarify whether histological parameters reflected tumor aggressiveness in patients with hepatocellular carcinoma (HCC). The tumor volume doubling times (TVDTs) of 21 HCCs, less than 3 cm in diameter at the start of the observation period, were calculated in 21 patients in whom the natural progression of the lesion was observed by ultrasonography. Paraffin-embedded sections were prepared from samples obtained by ultrasound-guided fine-needle liver biopsy at the end of the observation period. The histological parameters examined were the MIB-1 labeling index (LI), for which we performed immunohistochemical staining with the MIB-1 monoclonal antibody, using an antigen retrieval method; the nucleo-cytoplasmic (N/C ratio), cellularity, and the nuclear form factor (NFF), were calculated with an imaging analyzer. We performed multiple regression analysis for estimating the growth of small HCCs. With the N/C ratio (0.154 +/- 0.068; mean +/- SD), cellularity (453 +/- 21.8 cells/10(4) microm2), NFF (1.150 +/- 0.096), and degree of HCC differentiation as independent variables, only the MIB-1 LI (11.8 +/- 6.1%) showed a significant correlation with TVDT (207.5 +/- 162.6 days) (r = -0.658; P < 0.05). Compared to the conventional indices of histological atypism tested, i.e., N/C ratio, cellularity NFF, and degree of HCC differentiation, only MIB-1 LI was significantly correlated with small HCC growth rate. The MIB-1 LI may therefore be a simple and useful index of tumor aggressiveness.

Aged↗

Local hypercoagulative activity precedes hyperfibrinolytic activity in the subdural space during development of chronic subdural haematoma from subdural effusion.

The involvement of coagulation and fibrinolysis in the development of chronic subdural haematoma (CSH) from subdural effusion was investigated. Subdural fluid and venous blood samples were obtained from 34 patients with CSH and 9 patients with subdural effusion, and analyzed using enzyme-linked immunosorbent assays for thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), tissue factor, tissue factor pathway inhibitor (TFPI) and D-dimer. CSH was classified into the layering type, believed to be active, and other types according to x-ray computed tomography. All markers in the blood of both patient groups were similar to the values of normal subjects. Levels of TAT and F1 + 2 were much higher in the subdural fluid than in the blood of patients with CSH (P < 0.001, P < 0.001) and with subdural effusion (P < 0.05, P < 0.05). The level of D-dimer in the subdural fluid was significantly higher than in the blood (P < 0.001) in patients with CSH, but not in patients with subdural effusion. All markers in the subdural fluid of layering type CSH, except TFPI, were significantly higher than in the other types (P < 0.05). Local hypercoagulative activity in the subdural space is present in subdural effusion and precedes hyperfibrinolytic activity in CSH. Thrombin generation as indicated by TAT and F1 + 2 might be involved in the development of CSH. Propagation of CSH may be modulated by the coagulation system including the extrinsic pathway and fibrinolysis.

Adult↗

Analysis of the EEG bispectrum, auditory evoked potentials and the EEG power spectrum during repeated transitions from consciousness to unconsciousness.

We have compared the auditory evoked potential (AEP) index (a numerical index derived from the AEP), 95% spectral edge frequency (SEF), median frequency (MF) and the bispectral index (BIS) during alternating periods of consciousness and unconsciousness produced by target-controlled infusions of propofol. We studied 12 patients undergoing hip or knee replacement under spinal anaesthesia. During periods of consciousness and unconsciousness, respective mean values for the four measurements were: AEP index, 60.8 (SD 13.7) and 37.6 (6.5); BIS, 85.1 (8.2) and 66.8 (10.5); SEF, 24.2 (2.2) and 18.7 (2.1); and MF, 10.9 (3.3) and 8.8 (2.0). Threshold values with a specificity of 100% for a state of unconsciousness were: AEP index, 37 (sensitivity 52%); BIS, 55 (sensitivity 15%); and SEF, 16.0 (sensitivity 9%). There was no recorded value for MF that was 100% specific for unconsciousness. Of the four measurements, only AEP index demonstrated a significant difference (P < 0.05) between all mean values 1 min before recovery of consciousness and all mean values 1 min after recovery of consciousness. Our findings suggest that of the four electrophysiological variables, AEP index was best at distinguishing the transition from unconsciousness to consciousness.

Aged↗

Usefulness and limitations of ultrasonography in the initial evaluation of blunt abdominal trauma.

BACKGROUND: In the assessment of blunt abdominal trauma, the reliability of ultrasonography (US) in identifying individual organ injuries remains uncertain, in spite of its usefulness in detecting hemoperitoneum. This study was designed to evaluate the overall diagnostic value of US, including identification of individual organ injuries. METHODS: The accuracy of US in the detection of intra-abdominal injuries and the identification of individual organ injuries was evaluated in 1,239 patients seen during a 15-year period. Accuracy was based on detection of intraperitoneal fluid, free air, or irregular parenchymal lesions. RESULTS: For the detection of injuries, US was 94.6% sensitive, 95.1% specific, and 94.9% accurate. Individual organ injuries were identified with sensitivities of 92.4, 90.0, 92.2, 71.4, and 34.7% for the liver, spleen, kidneys, pancreas, and intestine, respectively. CONCLUSION: US is reliable for the detection of injuries and the identification of solid-organ injuries despite its poor sensitivity for intestinal injuries.

Abdominal Injuries↗

Discrimination among the clinical isolates of Candida albicans by amplification of the repetitive sequences, alts.

A primer pair, PB and BSH, which amplified alts, a portion of Candida albicans-specific repetitive sequence, RPS, gave stable and reproducible fingerprint patterns of the strains by polymerase chain reaction (PCR). We applied this method to clinical isolates of C. albicans for strain discrimination. Using PCR fingerprint patterns, we could analyze the relatedness of C. albicans strains including those isolated from children with leukemia and their bedside parents. The results indicated that PCR analysis targeting an alt region gives rise to the same conclusion as the previous study obtained by SmaI RFLP analysis.

Candida albicans↗

Spectroscopic investigation on the interaction of NCA0424, a potent antitumor indoloquinoxaline derivative, with DNA.

NCA0424 (1), an indoloquinoxaline derivative, has a potent antitumor activity against in vitro and in vivo tumor models. To elucidate its structure-activity relationship, the interactions with various B-form DNAs were investigated by thermal denaturation, viscosity and circular dichroism (CD) measurements. The thermal stability of the DNA duplex was increased by the interaction with 1, and preferable binding for alternative purine-pyrimidine base sequence was suggested. Comparative viscometric measurements with ethidium bromide (an intercalator) and distamycin (a minor groove binder) suggested that 1 is an intercalator. The interaction of DNA with 1 revealed a new CD band at 340-390 nm. Taking advantage of this induced CD band, the equilibrium binding constants were determined for various DNAs, and the binding preference of 1 for the alternative purine-pyrimidine base sequence, especially for the case of guanine as purine base, was indicated. The appearance of the induced CD band implies the importance of 1 side chain for the effective and/or stable intercalation of the aromatic ring into the DNA base pair.

Antineoplastic Agents↗

Expression of type XVII collagen alpha 1 chain mRNA in the mouse heart.

The type XVII collagen alpha 1 chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix (ECM) maintenance and signal transduction between the cell and the ECM. We examined the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Northern blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for alpha 1 (XVII) collagen. RT-PCR: Total RNA was extracted from 7 embryos, 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and MMLV. Amplification was carried out in alpha 1 (XVII) collagen and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the alpha 1 (XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of alpha 1 (XVII) were 0.91 +/- 0.20 in the embryonic heart, 0.36 +/- 0.20 in the neonatal heart and 0.96 +/- 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen alpha 1 chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart.

Angiotensin-Converting Enzyme Inhibitors↗

Mechanisms of increased intracranial pressure in rabbits exposed to head-down tilt.

Changes in intracranial pressure (ICP) resulting from head-down tilt (HDT) were studied in rabbits, and a possible role of edema formation in the change of ICP was examined. Animals were anesthetized with pentobarbital sodium and artificially ventilated. ICP was continuously monitored through a catheter inserted into the subarachnoid space. It increased depending on the tilt angle and decreased when the tilt angle was reduced. ICP elevated from 4.6 +/- 0.7 mmHg (mean +/- standard error of the mean) at horizontal prone position to 13.7 +/- 1.0 mmHg immediately after the onset of 45 degrees HDT and gradually reduced toward the pre-HDT baseline in the next 8 h. ICP decreased below the pre-HDT baseline value immediately after returning to the horizontal prone position, and gradually increased toward the baseline during the 2 h of recovery period. Histological examination (HE stain) demonstrated that exposure to 8 h of HDT did not cause remarkable edema in either the gray matter or the white matter in rabbits. Water content and specific gravity of brain tissues both were increased in the HDT group in comparison with the control group. These results suggest that edema formation plays little role in the elevation of ICP during the acute phase of HDT in rabbits.

Animals↗

Modulatory role of protein tyrosine kinase activation in the receptor-induced contractions of the bovine cerebral artery.

Changes in contractile force were measured during isometric contraction of the bovine middle cerebral artery caused by stimulation of various receptors and by application of high K+, caffeine, and protein kinase C (PKC)-activators. The protein tyrosine kinase (PTK)-inhibitors, such as genistein and tyrphostin, were applied before testing the effect on the contractions or during the maximal plateau of the contraction. The contractions induced by serotonin, prostaglandin F2 alpha, endothelin-1, and thromboxane A2 were significantly and dose-dependently depressed by the PTK-inhibitors (IC50 2-15 microM). In contrast, contractions were significantly augmented by 1 microM pervanadate, an inhibitor of phosphoprotein tyrosine phosphatase. Lineweaver-Burk plotting of the dose-response curves with an increase in inhibitor concentration indicated that the receptor affinity for each agonist remained unchanged in spite of marked depression of the responses. Although the effect was not significant, contractions induced by both high K+ and caffeine were also depressed slightly by PTK-inhibitors in the same range of concentrations used for receptor-induced contractions. Contractions induced by PKC-activators, such as 1-oleoyl-2-acetyl-sn-glycerol and phorbol-12,13-diacetate, were significantly depressed by PTK-inhibitors at concentrations similar to those used for receptor-induced contractions. The results suggest that receptor stimulations which produce sequential activation of phospholipase C and PKC can activate PTK and trigger the so-called "PTK-cascade" causing a sustained or long-lasting contraction similar to the cerebral vasospasm observed clinically.

Animals↗

Basal perforating artery aneurysm within the cavum septi pellucidi. Case report.

The authors describe the case of a 16-year-old boy presenting with clinical onset of subarachnoid hemorrhage. The patient was found to have a small aneurysm arising from the distal portion of a basal perforating branch of the anterior cerebral artery (ACA), lying within a cavum septi pellucidi. Neuroimaging demonstrated a hematoma within the cavum septi pellucidi and the aneurysm was resected via a transcallosal approach guided by an intraoperative portable digital subtraction angiography (DSA) system. The origin of the aneurysm was presumed to be idiopathic. This report is the first to describe an aneurysm of a basal perforating artery arising from the ACA that resulted in an intracaval hematoma. When approaching small vascular lesions during surgery, intraoperative DSA is the method of choice to identify the precise trajectory and distance to the lesions.

Adolescent↗

[Immunohistochemical study on pulmonary neuroendocrine cells containing calcitonin gene-related peptide in sudden infant death syndrome].

To examine whether pulmonary neuroendocrine cells (PNEC) is associated with sudden infant death syndrome (SIDS), distribution and function of PNEC were investigated in infants from one to twelve months of age, including 19 cases with SIDS and 18 control cases without congenital heart disease and premature birth. In this study, lung tissue sections were immunostained with antibodies against chromogranin A (CGA) and calcitonin gene-related peptide (CGRP). Although the positivity of CGA in SIDS cases was not significantly different from that in control, the positivity of CGRP in SIDS cases was lower than that in control cases among one to four months old (p < 0.05). Our results suggest that respiratory and/or circulatory regulation of cases with SIDS is disturbed by reduction of CGRP expression, because CGRP is well known to be a vasodilator, a neurotransmitter and a promoter for proliferation of epithelium in airways.

Calcitonin Gene-Related Peptide↗

[Allergic granulomatous angiitis associated with cerebral infarction, myo-pericarditis and acute respiratory failure due to eosinophilic pneumonia].

We encountered a 23-year-old woman with allergic granulomatous angiitis (AGA) associated with cerebral infarction, myo-pericarditis, and acute respiratory failure due to extended eosinophilic pneumonia. She underwent emergency treatment at our hospital because of right hemiparesis and impaired consciousness. AGA was suspected because the patient had a history of bronchial asthma accompanied by pulmonary infiltrations with eosinophilia, and presented with diffuse pulmonary infiltrates, pericardial effusion, diffuse hypokinesis of myocardium, cerebral infarction and marked peripheral eosinophlia. Pulmonary eosinophilia was confirmed by examination of broncho-alveolar lavage fluid. Myocardial tissue biopsy specimens revealed fibrous granulation indicative of myocarditis. The patient responded well to corticosteroid therapy.

Acute Disease↗

Interaction of mutagenic tryptophan pyrolysate with d(CGATCG)2: intercalation model based on NMR experiments.

The solution structure of the complex of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), a potent mutacarcinogen isolated from tryptophan pyrolysate, with the hexamer duplex d(CGATCG)2, was analysed by 1H-NMR spectroscopy and molecular dynamic calculation. Trp-P-1 was intercalated between the CpG base pairings in a suitable manner to form the guanosine-Trp-P-1 adduct which corresponds to the major reactant of Trp-P-1 with DNA.

Base Composition↗

Direct detection of hepatitis B virus gene integrated in the Alexander cell using fluorescence in situ polymerase chain reaction.

Prolonged infection of hepatitis B virus (HBV) is reported to cause hepatocellular carcinoma (HCC) via liver cirrhosis. However, it is still unknown whether the HCC is induced by the HBV DNA integration or by inflammatory stimulation during the phase of liver cirrhosis. The aim of this study is to determine the intracellular or intranuclear distribution of HBV DNA with a highly sensitive assay. Here we directly detected the integration of HBV DNA by fluorescence in situ polymerase chain reaction (FISPCR). Since FISPCR products directly incorporate rhodamine-4-dUTP, the nucleus of Alexander cells integrated with HBV gene reacted with the HBV primers emits obvious fluorescence. The fluorescence values which were measured with an imaging analyzer show a significant difference between Alexander cells as compared to the controls. In conclusion, the target sequences of HBV were specifically amplified as fluorescent DNA after the present FISPCR procedure. This method could provide a novel and simple strategy for determining the quantitative role of viral DNA integration in oncogenesis.

Carcinoma, Hepatocellular↗

Reorientation of large DNA molecules in concentrated polyacrylamide solution during crossed-field electrophoresis.

Recently, we found that, in concentrated neutral solutions, DNA molecules migrate in linear conformation under steady electric field. In this paper, we report the conformational change of DNA during 120 degree crossed-field electrophoresis in the same polymer solution. We found that, in concentrated polyacrylamide solutions, the reorientation process of DNAs becomes simple: the DNA goes back along the previous track and the reorientation time is longer for larger DNA. Such a backtrack motion has been thought to be an essential motion for the separation of DNA fragments in pulsed field gel electrophoresis. We expect that this phenomenon is useful for a more efficient separation technique of large DNAs than the current pulsed field gel electrophoresis.

Acrylic Resins↗

Difference in gene expression for matrix metalloproteinase-1 between early and advanced hepatocellular carcinomas.

The histological observation that well-differentiated cancer cells in early hepatocellular carcinoma (HCC) invade portal tracts and/or fibrous bands and that these fibrous tissues then disappear suggests the participation of matrix metalloproteinase-1 (MMP-1) in the degradation of fibrous tissue. To confirm this hypothesis, the authors investigated the localization of both the MMP-1 protein and its messenger RNA (mRNA) in early HCC immunohistochemically and by in situ hybridization using complementary DNA (cDNA) and synthetic antisense probe of MMP-1; they then compared the results with those in advanced HCC. MMP-1 gene transcripts and protein were observed in well-differentiated cancer cells of early HCC but not in moderately or poorly differentiated cancer cells. Thus, cancer cells producing MMP-1 in early HCC may destroy the portal tract tissue adjacent to the cancer lesion and/or the fibrous band of cirrhosis. These results seem to have demonstrated a difference in the mechanism of cancer growth and invasion between early and advanced HCCs.

Adult↗

Fibrinolytic activity in the CSF and blood following subarachnoid haemorrhage.

Fibrinolytic agents are administered to resolve subarachnoid clot, a major reservoir for spasmogen, to prevent delayed cerebral vasospasm (VS) in patients with subarachnoid haemorrhage (SAH). However, intracranial bleeding often occurs, which may be caused by over-activation of fibrinolysis in the cerebrospinal fluid (CSF) milieu. We measured the levels of D dimer in the CSF and blood of patients with SAH to analyse the correlation between fibrinolytic activity and VS. CSF and blood samples were obtained three times, and VS was identified by angiography. The levels of D dimer in the CSF were significantly higher than in the blood, but changes with time were inverse. Patients with VS showed significantly lower levels of D dimer in both CSF and blood in the initial stage compared to those without VS. These observations suggest that monitoring of fibrinolytic activity in the CSF to identify patients eligible for additional fibrinolytic treatment could reduce the risk of VS and iatrogenic intracranial bleeding.

Adult↗