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Biomedical subjects

N Hirota

Publications and source records attributed to N Hirota.

At least 19 recordsLinked to original sources
PubMed2001

The physiological basis of conduction slowing in ALS patients homozygous for the D90A CuZn-SOD mutation.

Familial amyotrophic lateral sclerosis (ALS) with the autosomal-recessively inherited D90A CuZn-superoxide dismutase (CuZn-SOD) mutation is characterized by a stereotypic slowly progressive, distinctive phenotype and very slow central motor conduction. To determine the basis of this slowing, we assessed corticomotoneuronal function using peristimulus time histograms (PSTHs) in 8 ALS patients homozygous for the D90A CuZn-SOD mutation. The results were compared with findings in 10 patients with multiple sclerosis (MS), in which slowing of central motor conduction is common, and 11 healthy subjects. PSTHs were constructed from 3-7 different, voluntarily recruited motor units recorded in each patient from the extensor digitorum communis muscle (EDC). In D90A and MS patients, the stimulus threshold, onset latency, number of excess bins, duration, amplitude, and synchrony of the primary peak differed significantly from controls (P < 0.0004). The mean onset latency of the primary peak in D90A patients was 35.3 ms, compared to 23.6 ms for MS patients and 19.3 ms for normal subjects (P < 0.0001). In the D90A patients, the onset latencies of the primary peak had a bimodal distribution, whereas in MS the distribution showed a continuum. Loss of synchrony was similar in D90A and MS patients, but the threshold, number of excess bins, and duration differed significantly (P < 0.0057), which suggests that either axonal loss or demyelination can result in delayed and desynchronized primary peaks. We propose that conduction slowing in the D90A homozygotes results from selective loss of fast-conducting large pyramidal cells with preservation of slow-conducting mono- or polysynaptic corticomotoneuronal connections.

Adult↗
PubMed2001

Intracranial electroencephalographic changes in deep anesthesia.

OBJECTIVE: It is well known that electroencephalograms (EEGs) show electrical silence in deep anesthesia as well as brain death. This is the first report on intracranial EEG changes in deep anesthesia. METHODS: We developed a new direct brain monitoring system capable of recording intracranial EEGs. This study included 13 patients with head trauma or cerebrovascular accident under deep anesthesia. RESULTS: The intracranial EEGs showed different patterns of wave activity in depth compared with the cortical surface. In 3 of the cases, the scalp EEG showed a flat tracing at 2.0-2.5% of isoflurane. In two of the cases, the intracranial EEGs showed electrical silence when the scalp EEG was flat. Decreasing the concentration of isoflurane to 1.5%, the intracranial EEG showed single paroxysmal appearance of 'revival' theta waves on the electrocorticogram (ECoG) or electroventriculogram (EVG). The intracranial 'revival' wave was followed by high-voltage burst-waves. In another case, at 2.0-2.5% of isoflurane, the amplitude of the waves was greatest on the EVG. CONCLUSION: There is wave activity difference in the brain depth, which the scalp EEG is unable to show. Intracranial EEGs are able to show the first signs of revival after a nearly flat tracing in deep anesthesia.

Adult↗
PubMed2001

Superoxide inhibits neuronal nitric oxide synthase influences on afferent arterioles in spontaneously hypertensive rats.

This study was designed to determine the influence of increased superoxide anion in neuronal nitric oxide synthase (nNOS)-dependent regulation of afferent arterioles in spontaneously hypertensive rats (SHR). Afferent arteriolar diameters of male Wistar-Kyoto rats (WKY) and SHR were assessed in vitro with the blood-perfused juxtamedullary nephron technique and averaged 21.6+/-1.6 (n=6) and 18.8+/-1.2 (n=7) micrometer, respectively. The superoxide dismutase mimetic Tempol (1, 10, and 100 micromol/L) did not influence afferent arterioles of WKY but significantly increased afferent arteriolar diameters of SHR by 20.6+/-5.5%, 25.2+/-5.4%, and 23.3+/-4.9%, respectively. In WKY (n=6), the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 10 micromol/L) and the NOS inhibitor N(omega)-nitro-L-arginine (L-NNA; 100 micromol/L) significantly decreased afferent arteriolar diameters (19.6+/-1.6 micrometer) by 11.9+/-3.1% and 21.0+/-3.9%, respectively. In SHR (n=7), L-SMTC did not influence afferent arteriolar diameters (21.0+/-1.5 micrometer), but L-NNA exerted an afferent arteriolar constriction (14.8+/-3.2%) that was similar to the response observed in WKY. Experiments were also performed in the presence of 100 micromol/L Tempol. In afferent arterioles of WKY (n=6), Tempol treatment did not modulate the basal diameters (21.5+/-1.2 micrometer) or the constrictor response to L-SMTC (10.6+/-2.1%) or L-NNA (19.3+/-3.3%). In SHR (n=8), Tempol significantly increased afferent arteriolar diameters by 22.5+/-4.3% and enhanced afferent arteriolar constrictor responses to L-SMTC (18.4+/-2.7%) and L-NNA (31.9+/-2.6%). However, the nitric oxide donor S-nitroso-N-acetylpenicillamine (10 micromol/L), which similarly increased afferent arteriolar diameters (17.2+/-2.3%, n=6), did not affect afferent arteriolar responses to L-SMTC (1.5+/-2.7%) or L-NNA (18.6+/-2.3%). These suggest that superoxide anion inhibits the control of afferent arteriolar diameters by nNOS in SHR.

Animals↗
PubMed2000

Temporal dispersion of cortically evoked single motor unit potentials in ALS.

Peristimulus time histograms (PSTHs) can be used to investigate corticomotoneuronal dysfunction in amyotrophic lateral sclerosis (ALS). The most characteristic change is temporal dispersion of the primary peak. We recorded PSTHs in the extensor digitorum communis with voluntary motor units activation (standard PSTHs) or at rest (non-activated PSTHs). Standard PSTHs were recorded in 29 motor units of 12 healthy control subjects and 12 sporadic ALS patients. Double primary peaks were seen in three motor units of two healthy control subjects and 10 motor units from five ALS patients. The number of subpeaks was up to three in most of the normal motor units as well as in the earlier component of double primary peaks. The subpeaks were smaller and less discernible in the later component of double primary peaks. Non-activated PSTHs of ALS patients demonstrated similar decomposition of subpeaks in the motor units with significantly increased variability of latency. Similar findings in the standard PSTHs and non-activated PSTHs suggest that the abnormalities seen in ALS are independent of the membrane potential of the spinal motoneuron and therefore supraspinal in origin. The decomposed additional later component may indicate activation of slow conducting corticospinal tracts.

Amyotrophic Lateral Sclerosis↗
PubMed2000

The split hand in ALS has a cortical basis.

Loss of highly fractionated movement involving the thumb and index finger is an early characteristic of hand dysfunction in many ALS patients. These movements are largely subserved by the 'thenar complex' including the first dorsal interosseus muscle (FDI), whereas the 'hypothenar complex', innervated by the same myotome, has less ability to fractionate and is relatively spared. This suggests that in ALS, hand dysfunction and wasting is related to corticomotoneuronal representation and input. To determine whether corticomotoneuronal input to the thenar spinal pool is preferentially impaired compared to the hypothenar spinal pool in ALS, we studied 18 ALS patients and 11 normal subjects. Compound muscle action potentials (CMAPs) and motor evoked potentials (MEPs) of the thenar and hypothenar complexes were evoked by peripheral nerve stimulation and transcranial magnetic stimulation. In healthy control subjects the cortical/peripheral (MEP/CMAP) ratios were significantly larger for the thenar complex suggesting a stronger corticomotoneuronal input to this muscle complex (P<0.005). This was not the case in ALS patients. Comparing the ratios between control subjects and patients revealed a significant reduction for the thenar complex (P<0.02) in ALS patients but not for the hypothenar complex. We conclude that corticomotoneuronal input to the thenar complex is preferentially affected in ALS and that corticomotoneuronal disease may be the prime determinant of hand dysfunction and wasting.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Effect of maturation on nerve excitability in an experimental model of threshold electrotonus.

Threshold electrotonus (TE) is a new tool for investigating axonal function noninvasively in vivo. To increase its potential clinical value, we developed a rat model of TE, and examined the effects of maturation and pharmacological intervention. We recorded TE in 92 male rats (body weight 90-650 g) by stimulating the motor nerve in the tail, and applying 100-ms conditioning currents. Motor conduction velocities increased up to a body weight of 330 g, and remained constant thereafter. TE in mature rats was similar to that in humans, and two parameters were analyzed: TEd(10-20) or the mean threshold reduction 10-20 ms after the onset of the depolarizing conditioning current at 40% of threshold intensity; and TEh(10-20) or the corresponding threshold decrease on hyperpolarization. Like latency, the absolute value of TEh(10-20) decreased up to 330 g, and then stabilized thereafter, probably reflecting the progressive increase in the axonal diameter and relative reduction in internodal impedance. In contrast, TEd(10-20) gradually decreased up to 330 g, and then jumped to a higher level, which was maintained for animals of >400 g. 4-Aminopyridine, a blocker of fast potassium channels, selectively increased TEd(10-20) only in the immature or young (<330 g) rats. This suggests that, in the mature animals, fast potassium channels become sequestrated from the nodal membrane and not activated in response to nodal depolarization. These findings indicate that mature rats (>400 g) may provide a useful experimental model for interpreting abnormal TE responses in humans, and provide evidence for nonlinear maturation of potassium channel function in myelinated axons.

4-Aminopyridine↗
PubMed2000

Complex fasciculations and their origin in amyotrophic lateral sclerosis and Kennedy's disease.

Complex fasciculations are common in patients with amyotrophic lateral sclerosis (ALS). Combined fasciculations, defined as a complex fasciculation consisting of two or more components that occur independently but also in combination with another component, also occur in ALS. To test the hypothesis that combined fasciculations originate at the supraspinal level, we analyzed 2681 fasciculation potentials from 17 patients with definite or probable ALS by the El Escorial criteria. Results were compared with 304 fasciculation potentials recorded from 6 patients with Kennedy's disease, in which the upper motoneurons are spared. The mean firing frequency of the fasciculations was 24.4 +/- 25.6 per minute in ALS, significantly higher than the 2.9 +/- 3.4 per minute found in Kennedy's disease (P < 0.0001). In ALS, the mean combination ratio (the number of times that a combined fasciculation occurred divided by the total number of fasciculations) was 4.6 +/- 8.3% (range 0-33). Fourteen of 17 ALS patients had combined fasciculations, but only one combined fasciculation was found in a patient with Kennedy's disease. Combined fasciculations are distinctive in ALS, and we hypothesize that they are triggered by a supraspinal mechanism reflecting dysfunction of descending motor pathways.

Electromyography↗
PubMed1999

Hepatitis C virus structural proteins induce liver cell injury in transgenic mice.

To develop an animal model of hepatitis C virus (HCV) infection, transgenic mice carrying part of the HCV cDNA (C980) encoding HCV-core and envelope proteins under control of the mouse class I major histocompatibility complex gene (H-2K) regulatory region were produced. HCV-C980 RNA and HCV-core protein were present in livers from line H36 as determined by RNase protection assay and immunostaining, respectively. More than 40 animals from line H36 were examined histologically. Most of these H36 mice after 10 months of age developed spontaneous focal infiltration of lymphocytes, hepatocyte necrosis, degeneration, and altered foci with mitotic hepatocytes. These pathological lesions were absent in livers from the age-matched control littermates. Liver cells from these H36 mice were sensitive to damage induced by intravenous administration of an anti-Fas antibody. It is suggested that HCV-C980 proteins by themselves may be one causative agent of liver cell injury in subjects with HCV infection.

Animals↗
PubMed1999

Bactericidal activities of essential oils of basil and sage against a range of bacteria and the effect of these essential oils on Vibrio parahaemolyticus.

Basil and sage essential oils were examined for bactericidal activity against a range of Gram-positive and Gram-negative bacteria by viable count determinations. Generally, Gram-positive bacteria showed higher resistance to basil and sage essential oils than Gram-negative bacteria. Vibrio species showed a high sensitivity to both essential oils. Stationary growth phase cells of selected bacteria showed higher resistance to these essential oils than exponential growth phase cells. Basil-resistant (b21) and sage-resistant (s20) strains of Vibrio parahaemolyticus were isolated. Both strains showed higher resistance to heat and H2O2 than parent strain. Conversely, heat-adapted V. parahaemolyticus also showed a higher resistance to these essential oils than nonadapted cells.

Colony Count, Microbial↗
PubMed1998

Group additive contributions to the alcohol-induced alpha-helix formation of melittin: implication for the mechanism of the alcohol effects on proteins.

Detailed analysis of the effects of alcohols on proteins and peptides is important because of its wide range of applications in many fields. Whereas melittin, a major component of honeybee venom, is unfolded in an aqueous environment, the addition of alcohols induces an alpha-helical structure. We used circular dichroism (CD) to compare the effects of various alcohols on melittin. Whereas the alpha-helical state was basically independent of alcohol species, the effectiveness of alcohols varied significantly. Among alkanols, the effectiveness was proportional to the bulkiness of hydrocarbon groups, indicating that the hydrocarbon group contributes positively to the alcohol effects. Comparison of alcohols with the same hydrocarbon group but a different number of hydroxyl groups showed that the hydroxyl groups contribute negatively to the alcohol effects. Comparison of several halogenols indicated that halogen increases the effectiveness in the order of F < Cl < Br. These results suggested that the effects of alcohol can be interpreted by the additive contributions of each of the constituent groups of the alcohol, which are proportional to the solvent-accessible surface area. However, for markedly effective alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol, the aggregation of alcohols was suggested to further enhance these effects. We have constructed equations for estimating the effectiveness of alcohols in inducing alpha-helical structure, which should also be useful for predicting the other effects of alcohols on proteins.

Alcohols↗
PubMed1998

Application of nitrite reductase from Alcaligenes faecalis S-6 for nitrite measurement.

The enzymatic reaction of nitrite reductase (NIR) from Alcaligenes faecalis S-6 was applied to the measurement of nitrite. NIR was immobilized on the surface of a gold electrode using filter paper and a dialysis membrane, and used as a working electrode in a three-electrode system. Amperometric methods were applied using NIR and the electron mediator 1-methoxy PMS (1-methoxy-5-methylphenazinium methylsulfate). The decrease in cathodic current showed a correlation to nitrite concentration over the range 0-1 mg/l. Measurements using a batch-flow type system gave a lower detection limit of 0.01 mg/l. This is sufficient for the detection of nitrite in natural waters.

Alcaligenes↗
PubMed1998

Isolated trigeminal nerve metastases from breast cancer: an unusual cause of trigeminal mononeuropathy.

BACKGROUND: Mononeuropathy of a cranial nerve caused by brain metastases rarely occurs in patients with a malignant neoplasm. Even after the development of computed tomography (CT) and magnetic resonance imaging (MRI), few cases of brain metastases resulting in trigeminal mononeuropathy have been reported. We report a case of trigeminal mononeuropathy caused by a brain metastases that was detected on CT and MRI preoperatively, and was successfully treated by microsurgery and radiation. CASE DESCRIPTION: A 49-year-old woman with a history of breast cancer complained of right facial pain. CT and MRI revealed a brain tumor in the right Meckel's cave and cerebellopontine angle. She underwent surgery, and the diagnosis was metastatic breast cancer. No recurrence was detected on MRI performed 2 years after the resection and radiation of the tumor. CONCLUSIONS: Most of the reported cases of brain metastases causing a mononeuropathy occurred before the availability of CT; the mononeuropathy was diagnosed by neurologic or postmortem examination. Even after the development of CT and MRI, few cases of brain metastases resulting in trigeminal mononeuropathy have been reported. If such patients do not manifest symptoms of brain metastases other than the mononeuropathy, it is difficult to make the correct diagnosis without CT and MRI. Physicians must be aware of mononeuropathy as an uncommon presenting symptom of brain metastases.

Breast Neoplasms↗
PubMed1998

Angiographic documentation of de novo aneurysm--case report.

A 49-year-old female presented with a case of de novo aneurysm which was documented angiographically 10 years after the initial aneurysm rupture. The de novo aneurysm arose as a blister-like aneurysm from a previously normal location 7 years after the first ictus. The de novo aneurysm progressed to a saccular aneurysm and ruptured after another 3 years. We recommend late angiography in high-risk patients to prevent repeat ictus.

Aneurysm, Ruptured↗
PubMed1998

[Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the treatment of elderly patients with pneumonia].

Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days. 1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No statistical differences were noted in the patients' backgrounds of either group. 2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases). This was found to be statistically significant (Fisher's exact test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination. 4. No side effects were observed in the study. 5. Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No statistical differences were noted in both groups. These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

Aged↗
PubMed1997

Cooperative alpha-helix formation of beta-lactoglobulin and melittin induced by hexafluoroisopropanol.

Alcohols denature the native state of proteins, and also stabilize the alpha-helical conformation in unfolded proteins and peptides. Among various alcohols, trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) are often used because of their high potential to induce such effects. However, the reason why TFE and HFIP are more effective than other alcohols is unknown. Using CD, we studied the effects of TFE and HFIP as well as reference alcohols, i.e., methanol, ethanol, and isopropanol, on the conformation of bovine beta-lactoglobulin and the bee venom melittin at pH 2. Upon addition of alcohols, beta-lactoglobulin exhibited a transformation from the native state, consisting of beta-sheets, to the alpha-helical state, whereas melittin folded from the unfolded state to the alpha-helical state. In both cases, the order of effectiveness of alcohols was shown to be: HFIP > TFE > isopropanol > ethanol > methanol. The alcohol-induced transitions were analyzed assuming a two-state mechanism to obtain the m value, a measure of the dependence of the free energy change on alcohol concentration. Comparison of the m values indicates that the high potential of TFE can be explained by the additive contribution of constituent groups, i.e., F atoms and alkyl group. On the other hand, the high potential of HFIP is more than that expected from the additive effects, suggesting that the cooperative formation of micelle-like clusters of HFIP is important.

1-Propanol↗