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Biomedical subjects

M Ishikawa

Publications and source records attributed to M Ishikawa.

At least 145 records · Page 8Linked to original sources

Intraoperative microwave coagulation therapy for large hepatic tumors.

We report new surgical techniques for intraoperative microwave coagulation therapy (IMCT), conducted in three patients with large liver neoplasms with poor liver function or difficult tumor location. Anterolateral thoracotomy was performed for tumors in the right lobe to obtain a good operative field. Four electrode needles were inserted for microwave irradiation, with settings of 60 W, 45 s for coagulation and 1 s for dissociation. Clamping of the hepatoduodenal ligament was performed during IMCT. We began the coagulation at the bottom of the tumor, irradiating the tumor and the surrounding parenchyma to create regional necrosis with a safe margin. With these methods, we treated two women diagnosed with large hepatocellular carcinoma with liver cirrhosis and a man with liver metastasis from rectal cancer. The postoperative course of these patients was uneventful. A marked low-density area was seen in the region of therapy and no enhanced findings were observed on enhanced computed tomography postoperatively. However, in one patient, transcatheter embolization (TAE) was performed 1 month postoperatively because recurrence was noted on the bottom of the tumor. Thus, IMCT destroys the peripheral part of the tumor that may remain viable after TAE, but combination therapy with TAE is preferable, especially when a viable part exists within tumors. IMCT is an active, safe, and nontoxic therapeutic modality for large hepatic tumors, and is particularly applicable in patients with large hepatocellular carcinomas and poor liver function.

Aged↗

DNA fragmentation in central nervous system vascular malformations.

Recent studies have shown that apoptosis plays an important role in vascular remodeling. We examined central nervous system vascular malformations for the presence of DNA fragmentation which is the evidence of apoptosis. We hypothesize that vascular remodeling through apoptosis may be responsible for recurrence or hemorrhage in these lesions. We examined the specimens of central nervous system vascular malformations by in situ end labeling (ISEL) of fragmented DNA. Moreover, we examined the expression of Caspase-3 which is apoptosis-related proteins in these lesions by immunohistochemistry. DNA fragmentation was observed in all 15 arteriovenous malformation (AVM) specimens. ISEL-positive cells were mainly distributed in the endothelium, media and perivascular tissue. In cavernous hemangioma (CH), DNA fragmentation was also observed in all 5 specimens. ISEL-positive cells were distributed in the endothelium, subendothelium and intercavernous matrix. Thirteen out of 15 AVM lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was mainly distributed in the endothelium, media and perivascular tissue. This distribution was similar to that of ISEL positive cells. As for CHs, all 5 lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was distributed in the endothelium, subendothelium and intercavernous matrix. Our findings indicate that apoptotic cell death and vascular remodeling play a role in the development and maintenance of vascular malformations.

Adolescent↗

Expression of parathyroid hormone-related protein in human and experimental atherosclerotic lesions: functional role in arterial intimal thickening.

We investigated the expression of parathyroid hormone-related protein (PTHrP) in atherosclerotic lesions and the role of PTHrP in the development of arterial neointima formation. Immunohistochemical staining of PTHrP in the neointima of rat aorta produced by balloon injury and of rat femoral artery produced by non-obstructive polyethylene cuff placement, and in the atherosclerotic lesion of human coronary artery was performed using anti-human PTHrP-(1-34) antibody. Anti-muscle actin antibody, HHF-35, and anti-macrophage antibody, HAM-56, were used to identify smooth muscle cells and macrophages, respectively. Immunoreactivity of PTHrP was detected in the thickened intima of rat and human lesions where the predominant cell types were smooth muscle cells or macrophages dependently on the lesion type. In the next series of experiments, we examined the effect of PTHrP on the development of cuff-induced intimal thickening of rat femoral artery. Either PTHrP-(1-34) or PTHrP-(7-34), a PTH/PTHrP receptor antagonist, suspended in pluronic F-127 gel was locally applied around the rat femoral artery. Intimal thickening induced by cuff placement was evaluated 2 weeks later. PTHrP-(1-34) dose-dependently inhibited intimal thickening determined as intima/media ratio and % stenosis whereas PTHrP-(7-34) dose-dependently enhanced that. These results suggest that PTHrP, which is expressed in atherosclerotic lesions, inhibits the development of neointimal formation.

Analysis of Variance↗

Rule extraction by successive regularization.

Knowledge acquisition is, needless to say, important, because it is a key to the solution to one of the bottlenecks in artificial intelligence. Recently, knowledge acquisition using neural networks, called rule extraction, is attracting wide attention because of its computational simplicity and ability to generalize. Proposed in this paper is a novel approach to rule extraction named successive regularization. It generates a small number of dominant rules at an earlier stage and less dominant rules or exceptions at later stages. It has various advantages such as robustness of computation, better understanding, and similarity to child development. It is applied to the classification of mushrooms, the recognition of promoters in DNA sequences and the classification of irises. Empirical results indicate superior performance of rule extraction in terms of the number and the size of rules for explaining data.

Agaricales↗

Novel BCR-ABL transcript containing an intronic sequence insert in a patient with Philadelphia-positive acute lymphoblastic leukaemia.

In a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL), a novel variant of the chimaeric BCR-ABL mRNA transcript was detected by reverse transcription polymerase chain reaction (RT-PCR). Sequencing revealed the novel transcript to be a chimaeric mRNA produced by fusion of the BCR exon 14 (b3) to the ABL exon a2 with a 49-base pair (bp) insertion of an ABL intron 1b sequence between them. The insertion of the 49 bp introduced a stop codon. These data show that this variant of the chimaeric mRNA would not be translated into the p210 BCR-ABL protein. This could be one of the explanations as to why clinically the patient has responded well to therapy and continues to follow a mild clinical course.

Aged↗

Comparison of the somatogenic action of 20 kDa- and 22 kDa-human growth hormones in spontaneous dwarf rats.

The somatogenic action of the 20 kilodalton human growth hormone (20 K) was studied using the spontaneous dwarf rat (SDR), which has an isolated GH deficiency. Saline or 2.5 microg, 10 microg, or 100 microg/rat/day of recombinant 20 K or 22 K was administered to prepubertal male and female SDRs for 10 days. Their body weights, serum IGF-I, glucose and insulin were measured, and their body composition was determined. Body weights and serum IGF-I increased dose-dependently in both the 20 K- and 22 K-treated groups. There was no significant difference in body weights and serum IGF-I between the 20 K- and 22 K-treated groups except at the dose of 100 microg/rat, in which the IGF-I concentrations were higher in the 22 K-treated male SDRs (P< 0.05: 20 K vs 22 K). Blood glucose was not significantly different between the Spague-Dawley (SD) normal rats and the SDR control groups; however, serum insulin levels of the SDR were higher than those of the SD control group (P< 0.05). Additionally, there was a tendency for serum insulin and glucose levels to increase following 22 K treatment, but the differences were not significant. The percentage of body fat decreased with hGH treatment in both groups (P< 0.01: GH 10, 100 microg/rat group vs SDR control group), however, no significant differences were observed in body composition between the 20 K and 22 K treatment groups. In summary, the 20 K-hGH showed almost the same somatogenic activity as the 22 K-hGH in prepubertal male and female SDRs.

Animals↗

Enlarged entry space for the transpetrosal approach.

This report describes the removal of the roof of the external auditory meatus in approaching the tentorial edge, the cerebropontine angle, hippocampal brainstem lesions, and upper clival lesions. This procedure not only provides more space in approaching the tentorial edge or upper brainstem, it also provides a wider entry space for approaching posterior fossa lesions. This approach is also for lesions located lower than the tentorium or in the upper clivus. There is still some confusion about the method for removing the roof of the external auditory canal. We describe the clinical experience and comprehensive surgical procedures used on cadavers. Our extended temporal craniotomy technique using the removal of the roof of the external auditory meatus is a simple, safe, and useful method for obtaining a wider entry space to approach deep perimesencephalic lesions and the posterior fossa.

Journal Article↗

Inner ear anomaly of three-dimensional computed tomography: computed tomographic attenuation and image changes.

With regard to image diagnosis of inner ear anomalies, three-dimensional computed tomography (3D-CT) is useful in obtaining very realistic images that are unmatched by 2D-CT. Unlike the step scanning in the existing 2D-CT, in helical 3D-CT, scanning is performed in a spiral motion by continuously rotating the scanner and moving the table along the body axis at a constant speed. As a result, data obtained by this CT are continuous and very smooth curves can be obtained. Among the data, the CT attenuation determines the quality of the final 3D images. In the present paper, the usefulness of 3D-CT was investigated in a case with Mondini-type inner ear malformation.

Adult↗

Three-dimensional magnetic resonance imaging findings of inner ear anomaly.

Using three-dimensional magnetic resonance imaging (3D-MRI), the membranous labyrinth was examined in normal cases and in a case with bilateral Mondini-type inner ear malformations. Both ears were also examined by high-resolution computed tomography (CT) of the temporal bone. 3D-MRI provided more detail than findings obtained by conventional high-resolution CT and it enabled 3D observations to be made. Detailed examination of maximum intensity projection images along the cochlea axis revealed the cochlear turns in three dimensions.

Adolescent↗

Long latency response of the mentalis muscle following transcranial magnetic stimulation with a circular coil in normal subjects.

Short latency response (SLR), middle latency response and long latency response (LLR) are elicited in facial muscles by transcranial magnetic stimulation. Although it has been said that the LLRs are elicited by the trigeminal nerve stimulation, a trigeminofacial reflex is recorded easily in normal subjects by the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is more difficult to record in normal subjects. The aim of this study is to demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial magnetic stimulation, using a circular coil. The transcranial magnetic stimulations were performed over parieto-occipital scalp with frequencies of random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec and 9.1%, respectively. The waveform of the LLR varied trial to trial showing habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter muscle was not recorded following this transmagnetic stimulation. It was suggested that the LLR of the mentalis muscle is recorded by the transcranial magnetic stimulation of the trigeminal nerve with a circular coil. The ease and reliability of their recording make it possible to apply this LLR clinically as well as a blink reflex.

Adult↗

F-waves and facilitated late responses of the mentalis muscle in patients with a cerebrovascular accident.

F-waves in the extremities result from the backfiring of antidromically activated anterior horn cells and F-waves of the mentalis muscle can be also elicited after stimulation of the marginal mandibular branch of the facial nerve. In order to investigate the influence of the descending pathway of the excitability of the facial motonucleus, the F-wave of the mentalis muscle and the facilitated late response, which follows F-waves and which seems to be the snout reflex due to their similar latency and habituation, were studied in 11 conscious patients with a hemispheric cerebrovascular accident (CVA) presenting with hemiparesis, and in 10 unconscious patients with CVA or head injury. The duration and the persistence of the F-waves increased significantly statistically on the normal side in the CVA patients compared with those of the palsy side and the normal subjects. In comatose patients the F-waves and the facilitated late response were not elicited. The latency (46.1 +/- 13.3 msec) of the facilitated late responses in the unconscious patients tended to increase compared with the latency (36.6 +/- 4.3 msec) in the conscious patients. These findings suggest that the hyperexcitability of the facial motoneuron is ipsilateral to any hemispheric lesion; the hemispheric lesion exerts a bilateral excitatory influence on the interneuron of the facilitated late response: and that the reticular formation may influence the facial motoneuron and any interneurons concerned in the facilitated late response. F-waves and facilitated late responses should be further examined as neurophysiologically useful diagnostic methods.

Consciousness Disorders↗

A sequence motif involved in the donor substrate binding by alpha1,6-fucosyltransferase: the role of the conserved arginine residues.

Alpha1,6-fucosyltransferase catalyzes the transfer of fucose to the innermost GlcNAc residue of an N-linked oligosaccharide. In order to identify the amino acid residue(s) which are associated with the enzyme activity and to investigate their function, we prepared a series of mutant human alpha1,6-fucosyltransferases in which the conserved residues in the region homologous to alpha1,2-fucosyltransferase had been replaced. These proteins were then characterized by kinetic analyses. The wild-type and mutant alpha1,6-fucosyltransferases were expressed using a baculovirus-insect cell system. The activity assay showed that replacement of Arg-365 by Ala or Lys led to a complete loss of activity while substitution of Ala or Lys for the neighboring Arg-366 decreased the activity to about 3% that of the wild type. Kinetic analyses revealed that the replacements of Arg-366 lead to an increase in the apparent K (m) value for both GDP-fucose and the acceptor oligosaccharide but did not markedly affect the apparent V (max). When these mutants were inhibited by GDP in a competitive manner with respect to the donor substrate, the K (i) values were found to be 50-100 times higher than the value in the wild type. On the other hand, in the inhibition by GMP, the K (i) values for the mutants were very similar to that of the wild type. These findings suggest that Arg-366 contributes to the binding of GDP-fucose via an interaction with the beta-phosphoryl group of the GDP moiety of the donor, and that Arg-365 may also play an essential role in substrate binding. The results suggest that the motif common to alpha1,2- and alpha1,6-fucosyltransferases is critical for binding of the donor substrate, GDP-fucose.

Amino Acid Motifs↗

RecA-double stranded DNA complexes studied by atomic force microscopy.

RecA-double stranded (ds) DNA complexes have been studied by atomic force microscopy (AFM). When the complexes were prepared in the presence of ATP gamma S, fully covered RecA-dsDNA filaments were observed by AFM. When the concentration of RecA proteins was lower, various lengths of filaments were found. The variation of the observed structures may directly reflect the real distribution of the intermediate complexes in the reaction mixture, as the mixture was simply deposited on a mica surface for AFM observation without special fixation or staining. The use of a carbon nanotube (CNT) AFM tip enabled high resolution to reveal the periodicity of RecA-dsDNA filaments. Our observations demonstrated the potential of the AFM method for the structural studies of the RecA-dsDNA complexes, especially their intermediate states.

Adenosine Triphosphate↗

Method for stretching DNA molecules on mica surface in one direction for AFM imaging.

An efficient method was developed to stretch DNA molecules on an atomically flat surface for AFM imaging. This method involves anchoring DNA molecules from their 5' ends to amino silanized mica surfaces. N-Succinimidyl6-[3'-(2-pyridyldithio) propionamido]hexanoate (LC-SPDP), a heterobifunctional cross-linker with a flexible spacer arm was used for this purpose. The immobilization process was carried out by introducing a thiol group to the 5' end of DNA by PCR. Thiolated molecules were then reacted with the cross linker to conjugate with its 2-pyridyl disulphide group via sulfhydryl exchange. The resulting complex was deposited on amino silanized mica where NHS-ester moiety of the cross linker reacted with the primary amino group on the surface. Samples were washed by a current of water and dried by an air jet in one direction parallel to the surface. DNA molecules were shown to be fully stretched in one direction on imaging them by AFM.

Aluminum Silicates↗

Excitotoxic hippocampal injury is attenuated in thioredoxin transgenic mice.

Thioredoxin is a small, multifunctional protein with a redox-active disulfide/dithiol in the active site. Thioredoxin plays several important biologic roles both in intracellular and extracellular compartments with its redox-regulating and reactive oxygen intermediates scavenging activities. We assayed the seizure response and the excitotoxic hippocampal injury in thioredoxin transgenic and wild-type C57BL/6 mice. Seizure score after kainic acid treatment was significantly lower in thioredoxin transgenic mice. Seven days after kainic acid administration, the damage in the hippocampal CA1 and CA3 regions was significantly attenuated in thioredoxin transgenic mice. Thioredoxin and redox regulation play an important role in excitotoxic brain damage.

Animals↗

Genistein potentiates the relaxation induced by beta1- and beta2-adrenoceptor activation in rat aortic rings.

In rat aortic rings, genistein, an inhibitor of tyrosine kinase, but not daidzein, an inactive analogue of genistein, potentiated the relaxation induced by isoproterenol. Atenolol, a beta1-adrenoceptor antagonist, or ICI-118,551, a beta2-adrenoceptor antagonist, inhibited the relaxation induced by isoproterenol. The potentiating effect of genistein on the relaxation induced by isoproterenol in the presence of ICI-118,551 was apparently greater than that in the presence of atenolol. In the presence of ICI-118,551, theophylline, an inhibitor of cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE), markedly inhibited the potentiating effect of genistein on the isoproterenol-induced relaxation, whereas in the presence of atenolol, theophylline only partly inhibited the potentiating effect of genistein. The relaxation induced by forskolin, an activator of adenylyl cyclase, was potentiated by genistein or theophylline. In the presence of theophylline, the relaxation induced by forskolin was not further affected by genistein. Genistein also inhibited the activities of cAMP-PDE. In the presence of atenolol, but not ICI-118,551, iberiotoxin, an inhibitor of Ca-activated K channels, inhibited the relaxation induced by isoproterenol and the potentiating effect of genistein. In the presence of atenolol, quinacrine, an inhibitor of phospholipase A2, and metyrapone, an inhibitor of P-450 enzymes, but not alpha-naphthoflavone, an inhibitor of P-450 enzymes, indomethacin, a cyclooxygenase inhibitor, or AA861, a 5-lipoxygenase inhibitor, inhibited the potentiating effect of genistein. These results suggest that the potentiation of the beta1-adrenoceptor-induced relaxation by activation of genistein may mostly be due to inhibition of cAMP-PDE activities. In addition, the potentiation of the relaxation induced by activation of beta2-adrenoceptors by genistein may be related to the inhibition of arachidonic acid metabolism and cAMP-PDE activities.

Adrenergic beta-Agonists↗