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Biomedical subjects

H Iwasa

Publications and source records attributed to H Iwasa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Platelet aggregation during cardiopulmonary bypass evaluated by a laser light-scattering method.

BACKGROUND: In regard to postoperative bleeding, the most important consequence of cardiopulmonary bypass (CPB) is the loss of aggregability. However, the mechanism of platelet aggregation loss during CPB is unclear. Newly developed particle-counting methods that use light scattering can be used to quantify changes in the number of platelet aggregates of different sizes after application of an aggregating stimulus. Using a light-scattering method, we investigated changes in platelet aggregation during cardiac operation. METHODS: Nineteen patients undergoing CPB were evaluated. Blood samples were obtained before the operation, 1 hour after initiation of CPB, at the end of CPB, at the end of the operation, and on day 1 after the operation. Platelet aggregation after stimulation by 2.5 micromol/L adenosine diphosphate and 2.0 microg/mL collagen was determined; small (9 to 25 microm), medium (25 to 50 microm), and large (50 to 70 microm) aggregates were counted. RESULTS: Generation of medium and large aggregates after stimulation with adenosine diphosphate and collagen were significantly decreased with CPB, whereas, in spite of hemodilution, the quantity of the small aggregates was maintained at the elevated level. CONCLUSIONS: These results reflect the fact that CPB does not affect the first phase of aggregation. It suggests that platelet dysfunction associated with CPB is mainly caused by an inhibition in the development of small aggregates into larger aggregates.

Adult↗
PubMed1999

Event-related dynamics of the gamma-band oscillation in the human brain: information processing during a GO/NOGO hand movement task.

To investigate the gamma band activity relating to the discrimination process and motor behavior in the human brain, the event-related dynamics of the EEG spectrum was calculated during the visual GO/NOGO hand movement task and a control task (the visual element of the GO/NOGO task only) in eight subjects. The subjects were instructed to push (GO) or not to push (NOGO) a microswitch according to different visual stimuli and 21-channel scalp EEGs were recorded. The time courses of the power spectra after the stimuli were calculated using the fast Fourier transform for each condition (GO, NOGO and the control task), and were compared statistically between the conditions. The results suggested that a high gamma band oscillation, occurring at the frontal and left parieto-occipital areas at around 90 ms after the stimuli, relates to the discrimination process. Under the GO condition, this oscillation continued until 140 ms, and a subsequent oscillation occurred over the motor areas at around 200 ms, which seemed to be related to the motor action. On the other hand, under the NOGO condition, a low gamma band oscillation occurred in the central area at around 230 ms, which seemed to be related to the inhibition process.

Adult↗
PubMed1999

Differences in the width of the intercellular spaces in the epithelial basal infolding and the renal glomerular filtration site between freeze-substitution and conventional fixation.

After aldehyde prefixation, pretreatment with cryoprotectant and subsequent freeze-substitution with OsO4 in acetone (AC-FS), extensive gap junction-like close membrane appositions are frequently found in the basal infolding of the salivary gland epithelium, although the desmosomal intercellular space had the same width as with conventional electron microscopy. The intercellular space between podocyte pedicles and endothelial cells at the renal glomerular filtration site was narrower by the total width of 2 laminae lucidae following AC-FS than with conventional electron microscopy and was occupied by a homogeneous lamina densa without a lamina lucida, although no marked difference was discernable in the thickness of the lamina densa itself between the 2 preparative procedures. In addition, a decrease in the thickness of the glycocalyx was evident in the intestinal epithelial microvilli following AC-FS. It is thus likely that osmication in acetone at freezing temperatures remove the glycocalyx and related structures to a variable extent, and that this loss is responsible for reducing the intercellular spaces at some of the simple appositions narrower to the dimensions of the gap junction. It is also responsible for disappearance of the lamina lucida of the basement membrane.

Aldehydes↗
PubMed1999

[Effects of HCFU and TNP 470 on liver metastasis of BALB/c retroperitoneal sarcoma (LMFS)].

Combination therapy using HCFU and TNP 470, which inhibits angiogenesis, was examined for effectiveness against the footpad injection model of LMFS tumor. This LMFS, a retroperitoneal sarcoma of BALB/c mice, proliferated at the inoculation site (100% take) and all mice operated on after day 15 had spontaneous metastatic nodules in the liver. Mice with the LMFS tumor were given HCFU and 5-FU (5 days/week), and/or TNP 470 (3 days/week) from day 3 for 3 weeks and sacrified at day 28 under anesthesia. Seven of 10 mice receiving 5-FU and TNP 470 died from the side effects of the drugs. Mean tumor weight and liver metastatic nodules were determined and compared with a control group. The results were as follows: HCFU group: 94.6%, 11.8%, 5 FU group: 73.9%, 28.8%, TNP 470 group: 67.6%, 44%, HCFU and TNP 470 group: 33.3%, 6.4%. Mice with LMFS were given HCFU and/or TNP 470 from day 3 for 4 weeks. The foot on the injected side was amputated on day 15, and the animals were sacrified on day 35. Liver metastatic nodules compared with those of the operation (OP) group as follows: OP + HCFU group: 14.4%, OP + TNP group: 39.1%, and OP + HCFU + TNP 470 group: 5.4%. Histologically, 5 of 5 mice of the OP group, 3 of 5 of the OP + HCFU group, 4 of 5 of the OP + TNP 470 group and 1 of 5 of the OP + HCFU + TNP 470 group had liver metastases. These results show that while either HCFU or TNP 470 is effective by itself, a combination of these drugs is more effective against liver metastasis.

Angiogenesis Inhibitors↗
PubMed1999

Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver.

Human liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (DD) is involved in the metabolism of steroid hormones and polycyclic aromatic hydrocarbons, and is also responsible for the reduction of ketone-containing drugs. To account for the interindividual difference in the activity, we isolated and characterized clones for the human liver enzymes. The sequence of the cDNA clone coding for the variant differed from that coding for the wild-type DD by two nucleotides (substitutions of C with G at positions 434 and 931) which caused two amino acid replacements, Ser145 to Cys (S145C) and Leu311 to Val (L311V). The heterologous expression of the variant mRNA was confirmed in four of 31 liver samples from Japanese by an allele-specific polymerase chain reaction. The effects of the mutations on the catalytic properties were examined with the recombinant enzymes expressed in Escherichia coli. The introduction of S145C/L311V double mutations resulted in three- to five-fold decreased activities for xenobiotic and steroidal substrates, whereas no significant change was observed by an introduction of the S145C mutation alone. The results substantiate the existence of polymorphic forms for human liver DD, and also suggest the importance of the residue at position 311 for substrate binding to the enzyme.

Base Sequence↗
PubMed1998

Dipole source localization of ictal epileptiform activity.

Dipole source localization of ictal epileptiform activity recorded by scalp EEG was performed in patients prior to surgical treatment. The dipole tracing method combined with the scalp-skull-brain head model was used to locate epileptogenic foci. A digital EEG system was used for data collection. The accuracy of dipole source localization was evaluated by comparing the focus location with that obtained by chronic subdural electrocorticography. In a case of frontal lobe epilepsy with epileptogenic focus in the frontoparietal convexity, the results of dipole source localization agreed well with those obtained with chronic subdural electrocorticography. In a case of lateral temporal lobe epilepsy, the results of dipole source localization were consistent with those obtained with chronic subdural electrocorticography, but a small localization error was observed. The clinical usefulness of and suggestions for improving this method are discussed.

Adult↗
PubMed1998

Roles of the C-terminal domains of human dihydrodiol dehydrogenase isoforms in the binding of substrates and modulators: probing with chimaeric enzymes.

Human liver dihydrodiol dehydrogenase (DD; EC 1.3.1.20) exists in isoforms (DD1, DD2 and DD4) composed of 323 amino acids. DD1 and DD2 share 98% amino acid sequence identity, but show lower identities (approx. 83%) with DD4, in which a marked difference is seen in the C-terminal ten amino acids. DD4 exhibits unique catalytic properties, such as the ability to oxidize both (R)- and (S)-alicyclic alcohols equally, high dehydrogenase activity for bile acids, potent inhibition by steroidal anti-inflammatory drugs and activation by sulphobromophthalein and clofibric acid derivatives. In this study, we have prepared chimaeric enzymes, in which we exchanged the C-terminal 39 residues between the two enzymes. Compared with DD1, CDD1-4 (DD1 with the C-terminal sequence of DD4) had increased kcat/Km values for 3alpha-hydroxy-5beta-androstanes and bile acids of 3-9-fold and decreased values for the other substrates by 5-100-fold. It also became highly sensitive to DD4 inhibitors such as phenolphthalein and hexoestrol. Another chimaeric enzyme, CDD4-1 (DD4 with the C-terminal sequence of DD1), showed the same (S)-stereospecificity for the alicyclic alcohols as DD1, had decreased kcat/Km values for bile acids with 7beta- or 12alpha-hydroxy groups by more than 120-fold and was resistant to inhibition by betamethasone. In addition, the activation effects of sulphobromophthalein and bezafibrate decreased or disappeared for CDD4-1. The recombinant DD4 with the His314-->Pro (the corresponding residue of DD1) mutation showed intermediate changes in the properties between those of wild-type DD4 and CDD4-1. The results indicate that the binding of substrates, inhibitors and activators to the enzymes is controlled by residues in their C-terminal domains; multiple residues co-ordinately act as determinants for substrate specificity and inhibitor sensitivity.

Amino Acid Sequence↗
PubMed1998

The synchronization between brain areas under motor inhibition process in humans estimated by event-related EEG coherence.

To investigate the functional connection of brain areas under motor inhibition, the event-related coherence (ERCoh) of the electroencephalogram (EEG) was calculated for 10 subjects who were asked to perform a visual discrimination (GO/NO-GO) task. The subjects were instructed to push (GO) or not to push (NO-GO) a micro-switch according to different visual stimuli. Twenty-one-channel scalp EEGs were recorded and the surface Laplacians were calculated at F3, F4, C3, C4, P3 and P4 using the source derivation method. The time-courses of the inter- and intra-hemispheric coherence were calculated using the fast Fourier transform for each condition (GO or NO-GO), and were compared statistically between the two conditions. The results suggest that the ERCoh under the NO-GO condition consisted of two components; alpha band synchronization between bilateral frontal areas and theta band synchronization among bilateral frontal, central and parietal areas. It is likely that the former is related directly to the decision not to move, and the latter is related to the motor inhibition process.

Adult↗
PubMed1998

[Responsibility of the lateral geniculate nucleus in photosensitive epilepsy: dipole tracing method].

We studied the location of the electric generator of photoparoxysmal discharges using a scalp-skull-brain dipole tracing (DT) method. By this method, the location of epileptic discharges on each scalp EEG was calculated as an equivalent current dipole (ECD) in 8 cases of epilepsy who had photoparoxysmal discharges. We divided these cases into groups A and B (4 cases each), comprising of patients with and without visually-induced seizures, respectively. The ECDs of the 3 cases in group A corresponded to the small area adjacent to the lateral geniculate nucleus on MRI superimposed. On the other hand, the ECDs of all cases in group B located at the corpus callosum. This study suggests the pathways of epileptic discharges from the epileptic focus are different between two groups. It is supposed that neural activity of the lateral geniculate nucleus might be responsible for the generator mechanism of photoparoxysmal discharges which evokes photosensitive epilepsy.

Adolescent↗
PubMed1997

The time course of interhemispheric EEG coherence during a GO/NO-GO task in humans.

Event-related coherence of the EEG was calculated for 10 subjects performing a visual discrimination GO/NO-GO task. The subjects were instructed to push (GO) or not to push (NO-GO) a button according to visual stimuli. Twenty-one-channel scalp EEGs were recorded and the surface Laplacian was calculated using the source derivation method. The time courses of the coherence between F3 and F4, C3 and C4, and P3 and P4 were calculated using the fast Fourier transform for each task and were compared between conditions. Statistical analysis showed that coherence in the NO-GO condition became significantly higher than that in the GO condition between F3 and F4. The synchronization between bilateral dorsolateral frontal areas might therefore play an important role in the motor inhibition process.

Adult↗
PubMed1997

Involvement of two basic residues (Lys-270 and Arg-276) of human liver 3 alpha-hydroxysteroid dehydrogenase in NADP(H) binding and activation by sulphobromophthalein: site-directed mutagenesis and kinetic analysis.

A human liver 3 alpha-hydroxysteroid dehydrogenase isoenzyme, a member of the aldo-keto reductase family, shows a marked preference for NADP(H) over NAD(H), and is activated by sulphobromophthalein, which increases the Km values for both NADP(H) and substrates. Here we report kinetic alterations in binding of the coenzymes and the activator to the enzyme caused by site-directed mutagenesis of Lys-270 and Arg-276, which are strictly conserved among the aldo-keto reductase family of enzymes. The mutated enzymes, K270M and R276M, showed increases in the Km for NADP+ of 22- and 290-fold respectively; the Km for alcohol substrate and the kca1 of the NADP(-)-linked reaction were also elevated, by 9- and 5-fold respectively. No kinetic constant of the NAD(+)-linked reaction was altered by more than 3-fold. Calculation of the free-energy changes showed that the 2'-phosphate group of NADP+ contributes 16.3 kJ/mol (3.9 kcal/mol) of binding energy to its interaction with the wildtype enzyme, and the mutagenesis to K270M and R276M destabilized the binding energy of NADP+ by 6.3 and 13.0 kJ/mol (1.5 and 3.1 kcal/mol) respectively. In addition, the mutations attenuated enzyme activation by sulphobromophthalein, which bound to the mutant enzymes as an inhibitor. The inhibition for the R276M mutant was competitive with respect to NADP+ and non-competitive with respect to the substrate, whereas that for the K270M mutant was mixed-type, showing activation at coenzyme concentrations greater than 20 x Km. These results suggest that the two basic residues in the 3 alpha-hydroxysteroid dehydrogenase isoenzyme play crucial roles in binding both the negatively charged 2'-phosphate group of NADP+ and the sulphonic groups of sulphobromophthalein.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

The contribution of endogenous mono-ADP-ribosylation to kindling-induced epileptogenesis.

We examined the alteration of endogenous mono ADP-ribosylation in the hippocampus of amygdaloid kindled rats to clarify the neurochemical basis of epilepsy. A significant increase of the ADP-ribosylation on the 38 kDa protein was observed in the hippocampal membrane of the kindled rat. Several antiepileptics (phenytoin, phenobarbital, carbamazepine, sodium valproate) significantly decreased the ADP-ribosylation on the 38 kDa protein and effaced the increase in the kindled group. The ADP-ribosylation was largely increased by sodium nitroprusside, a nitric oxide generating compound, in both the kindled and control groups. Carbamazepine could not affect the ADP-ribosylation in the presence of sodium nitroprusside. Twenty amino acids from the N-terminus of the ADP-ribosylated 38 kDa protein were determined by sequential analysis. The sequence was completely identical to that of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that the endogenous mono-ADP-ribosylation which increased in the kindled group and decreased by the antiepileptics might be a specific reaction associated with the mechanisms of epileptogenesis.

Adenosine Diphosphate Ribose↗
PubMed1996

Alteration of G protein subclass mRNAs in methamphetamine-induced behavioral sensitization.

Guanine nucleotide-binding regulatory proteins (G proteins) play an obligatory role in the transmembrane signaling system and are concerned with the neurochemical basis of several psychiatric disorders. We examined the alteration in the mRNA levels of G protein subclasses (Gil alpha, Gi2 alpha and Go alpha) in behavioral sensitized rats using subchronic treatment with methamphetamine (MAP). Adult male Sprague-Dawley rats received intraperitoneal injections of MAP (4 mg/kg) or saline (control) once daily for 14 days. A remarkable increase in the levels of Gi2 alpha mRNA was observed in both sides of striatum at 48 hours after the last injection of MAP. The changes in the Gi2 alpha mRNA levels were not significant at two weeks after the last injection of MAP. The levels of Go alpha and Gil alpha mRNA were not changed at 48 hours and at two weeks after the last injection of MAP. These results suggest that the changes in the Gi2 mRNA level might be responsible for the reinforcement of the generation of stereotyped abnormal behavior by repeated administration of MAP rather than the persistence of the reverse tolerance phenomenon.

Animals↗
PubMed1996

Re-examination of the carotid body ultrastructure with special attention to intercellular membrane appositions.

Ultrathin sections of the carotid body of adult rats, processed through freeze-substitution after aldehyde-prefixation, showed a substantial number of presumed gap junctions between two adjacent chief cells, between chief and sustentacular cells, and between chief cells and carotid nerve terminals. The junctions showed a very narrow intercellular space of 2 nm and ranged in length from 200 nm to 1 micron. They may form the morphological substrate for electrical coupling between cells, the occurrence of which has been demonstrated by electrophysiology. Further studies using freeze-fracture and immunocytochemistry for connexins are necessary to confirm this possibility. In addition, small tight junctions are present between chief and sustentacular cells, and between adjacent sustentacular cells.

Animals↗
PubMed1996

Combined treatment of a dural arteriovenous malformation of the lateral sinus using transarterial and direct lateral sinus embolisation.

An 80-year-old man presented with a dural arteriovenous malformation (DAVM) involving the left lateral sinus. A carotid angiogram showed the lateral sinus to be occluded proximally and distally, with unusual retrograde venous outflow from the residual sinus to the cortical veins, including a dilated vein of Labbé. Single photon emission computed tomography showed reduced left frontal and temporal cerebral blood flow. We concluded that the risk of bleeding from the DAVM was high and that the patient needed to be treated immediately. However, his age made surgical removal of the DAVM hazardous and we therefore chose to treat him by transarterial and direct lateral sinus embolisation via a burr hole.

Aged↗
PubMed1995

MR in temporal lobe epilepsy: early childhood onset versus later onset.

PURPOSE: To study the relationship between the MR findings and the clinical features in temporal lobe epilepsy in childhood (less than 10 years of age). METHODS: MR studies were performed with a 1.5-T imager on 38 temporal lobe epilepsy patients receiving drug therapy at the psychiatric department. These patients were divided into two groups according to their age at onset (10 years or less, 11 years or more). The two groups were compared in terms of the MR findings and clinical features. RESULTS: The 11 younger-onset patients included 5 with a high-signal area attributed to mesial temporal sclerosis. Clinically, all of these 5 patients had a history of "complex" febrile convulsions, which sharply distinguished them from the older-onset group. CONCLUSION: The analysis suggests that complex febrile convulsions in infancy can be associated with high-signal areas on MR attributed to mesial temporal sclerosis.

Adolescent↗