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Biomedical subjects

M Kanda

Publications and source records attributed to M Kanda.

At least 91 records · Page 5Linked to original sources

Pain-related somatosensory evoked potentials can quantitatively evaluate hypalgesia in Wallenberg's syndrome.

In 6 patients with Wallenberg's syndrome who showed a dissociated loss of pain sense, we recorded pain-related somatosensory evoked potentials following CO2 laser stimulation of the hand dorsum (pain SEPs). Two components, N2 and P2, were recorded by stimulation of the unaffected hand, whereas on the affected side they were absent or decreased in proportion to the severity of hypalgesia which was evaluated by both needle test and CO2 laser stimulation. Latency of either component, if appeared, was longer in the affected hand stimulation than that in the unaffected one. In contrast, N20 of the conventional electrically-stimulated SEPs (electric SEPs) showed no difference between the two sides. It is concluded that, unlike other electrophysiological methods, pain SEPs following CO2 laser stimulation can quantitatively evaluate functional impairment of the spinothalamic tract in Wallenberg's syndrome.

Adult↗

Morphology of individual axons in crossed corticorubral projections in developing cats and effects of partial denervation.

Ordered neuronal connections in mature brains are thought to be sculpted from initially diffuse projections by elimination of inappropriate projections and strengthening of appropriate ones. Although evidence suggests that neuronal activity plays a role in these processes, the mechanism behind the modification of neuronal connections remains obscure. To gain insight into the mechanisms of axonal elimination and projection strengthening, we examined the morphology of individual axons that were to be eliminated as well as the consequences of partial denervation. While corticorubral projections in adult cats are thought to be uncrossed, early in postnatal development and after early unilateral lesions to the sensorimotor cortex, however, a significant amount of crossed corticorubral projections occurs. We examined the morphology of individual corticorubral axons in fetal cats and kittens from embryonic day 59 to postnatal day 48 and those that had received early unilateral lesions to the cortex, by serial reconstruction of Phaseolus-vulgaris-leucoagglutinin- or biocytin-labeled axons. For about 2 weeks during pre- and postnatal development, crossed axons remained simple in morphology, with few branches. Thereafter, they showed an increase in branch number, but then began to show fewer branches again. Axons and their collaterals were found in nonrestricted areas of the red nucleus (RN) throughout the period of observation, indicating that axons can sit at an inappropriate target for weeks but fail to ramify. In contrast, crossed corticorubral axons in kittens with cortical lesions showed terminal-arbor-like structures in the RN region that are in mirror symmetry to topographically appropriate areas in the ipsilateral RN, although some showed simple morphology without arbors. These complicated forms of morphology of individual axons during development and after partial denervation may not be explained by a simple activity-dependent mechanism.

Animals↗

[Familial Binswanger-type encephalopathy with Sneddon syndrome].

We reported a family with early onset cerebrovascular disease. Patient 1 (a 36-year-old man) demonstrated a combination of livedo reticularis and cerebral infarction as previously described as Sneddon syndrome. He also showed transient focal neurologic symptoms and mild dementia. Patient 2 (an elder sister of Patient 1) was suffering from migraine. Their father and paternal uncle died of cerebral infarction, which had developed in their thirties or forties. Patients 1 and 2 showed MRI findings compatible with encephalopathy with Binswanger-type. Contrary to the previous reports on Binswanger-type encephalopathy, both of these patients demonstrated decreased levels of fibrinogen as well as those of factor V, together with negative antiphospholipid antibody. Thus, juvenile onset, autosomal dominant inheritance, the diversity of clinical findings and the coagulopathy in this family were characteristic features. The level of thrombin-antithrombin III complex (TAT) was markedly increased in Patient 1. Treatment with antithrombin (argatroban 20mg i.v. everyday for 28 days) not only reduced the level of TAT but also improved the livedo reticularis and neurological findings. Although gene analysis has not been performed yet on this family, this condition is similar to cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), which involve juvenile cerebral infarction and dementia as well as migraine.

Adult↗

[The value of F-waves in an early electrodiagnosis of the lower cervical cord infarction].

In a case of infarction in the lower cervical spinal cord, F-waves were lost in the paralyzed hand muscles 48 hours after the onset, in spite of normal compound muscle action potentials (CMAP). Subsequently the amplitude of CMAP decreased markedly in size 14 days later, when needle EMG revealed acute denervation. At 11 days after the onset MRI demonstrated a linear lesion in the ventral portion of the lower cervical spinal cord suggesting ischemia. Thus, the loss of F-waves is useful in early diagnosis of the lower cervical spinal cord infarction, which reflects the decrease in the excitability of the anterior horn cells taking place soon after ischemic insult.

Action Potentials↗

Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the endothelium-independent and endothelium-dependent contraction in isolated canine cerebral arteries.

The inhibitory effects of NKY-722 (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0) on endothelium-independent and endothelium-dependent contractions were examined in comparison with nicardipine in isolated canine cerebral arteries. NKY-722 relaxed the cerebral arteries contracted endothelium-independently by KCl, prostaglandin F2 alpha U-46619 (a thromboxane A2 agonist) and endothelin-1 with IC50 = 2.5, 3.4, 2.8 and 3.6 x 10(-10) mol/l, respectively. On the basis of IC50 values, NKY-722 was about 2 times more effective than nicardipine. Pretreatment of NKY-722 and nicardipine inhibited the endothelium-independent contraction induced by KCl and serotonin to a similar degree. NKY-722 attenuated the endothelium-dependent contractions caused by acetylcholine (ACh), adenosine diphosphate and KO2 with IC50 = 1.7, 3.8 and 1.4 x 10(-9) mol/l, respectively. NKY-722 was about 2 times less effective than nicardipine. NKY-722 and nicardipine inhibited dose-dependently the endothelium-dependent contractions induced by hemolysate. NKY-722 was nearly equipotent to nicardipine on the phasic contraction and slightly more potent on the tonic contraction. The inhibitory effect of NKY-722 on the endothelium-independent contraction induced by KCl and the endothelium-dependent contraction induced by ACh were sustained for a longer time than that of nicardipine after repetitive wash-out. In conclusion, NKY-722 inhibited effectively the endothelium-independent and endothelium-dependent contractions in the cerebral arteries. The effect of NKY-722 was similar to, but longer-lasting than that of nicardipine.

Acetylcholine↗

Effects of 1-[3-(4-benzhydryl-1-piperazinyl)propyl]-3- (1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid with thromboxane A2 synthetase inhibitory and H1-blocking activities on anaphylactic bronchospasm.

1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )- 1H-indole-6-carboxylic acid (CAS 172544-75-1, KY-234) was characterized pharmacologically. KY-234 (10(-9)-10(-6) mol/l) and ozagrel (10(-8)-10(-5) mol/l) inhibited the production of thromboxane A2 (TXA2) in rabbit platelets. KY-234 and pyrilamine at concentrations of 10(-9)-10(-6) mol/l relaxed the isolated guinea pig trachea contracted with histamine, while neither drug attenuated the heart rate increased by histamine. Cimetidine antagonized histamine in the right atrium but not in the trachea. KY-234 (10(-8)-10(-5) mol/l) and ozagrel (10(-7)-10(-4) mol/l), but not pyrilamine, attenuated the contraction induced by leukotriene D4 (LTD4) and platelet-activating factor in the lung parenchymal strips. In anesthetized guinea pigs, KY-234 (1-10 mg/kg p.o.) inhibited the LTD4- and histamine-induced bronchoconstriction. Ozagrel and terfenadine inhibited only the LTD4- and histamine-induced constrictions. KY-234 (3-30 mg/kg p.o.) inhibited the anaphylactic bronchoconstriction continuously for 15 min after antigen-challenge. Terfenadine (3-30 mg/kg p.o.) inhibited the constriction more strongly within the first 5 min (fast phase) than it did within 5 to 15 min (slow phase) after the challenge. Ozagrel (100 mg/kg p.o.) slightly attenuated only the constriction during the slow phase. These findings demonstrated that KY-234 has a selective TXA2 synthetase-inhibitory and H1-blocking activity and protects against anaphylactic bronchospasm more effectively than a TXA2 synthetase inhibitor or H1-blocker alone.

Anaphylaxis↗

[Primary right atrial hemangiosarcoma manifesting as cardiac tamponade: a case report with transesophageal echocardiography].

A 39-year-old woman presented with a right atrial hemangiosarcoma manifesting as cardiac tamponade with complaints of chest discomfort and dyspnea. Transthoracic echocardiography revealed remarkable pericardial effusion and a right atrial mass. Transesophageal echocardiography disclosed the tumor extending into the right atrial cavity. Surgery found the tumor was poorly demarcated, immobile and adhered to the adjacent right atrial wall and septum. The echocardiographic findings correlated well with the surgical and autopsy findings.

Adult↗

Prenatal development of cerebrorubral and cerebellorubral projections in cats.

Cerebrorubral (CR) and cerebellorubral (CBR) afferents are localized to distal dendrites and somata of red nucleus (RN) neurons, respectively, in adult cat. To test if this synaptic site segregation is established by a sequential arrival of the two afferents, the development of CR and CBR projections was studied. CR axons arrived in the RN at embryonic day (E) 50 or 51, while CBR axons entered the RN before E35. These results suggest the possibility that arrival of CBR axons before CR axons leads to the segregation of synaptic sites.

Afferent Pathways↗

Perinatal development of action potential propagation in cat rubrospinal axons.

1. The development of action potential conduction was studied by intracellular recording of antidromic spikes in cat rubrospinal cells. 2. The distance between the C1 and L1 spinal segments increased linearly from 5.6 cm at embryonic day (E) 59 to 9.8 cm at postnatal day (P) 30. 3. The conduction time from the C1 segment to the rubrospinal neuron soma, estimated from antidromic spike latency evoked by stimulation of the C1 segment, decreased rapidly prior to birth and then slowly thereafter. This coincided with a reduction in conduction time variation between cells. 4. The conduction time from the red nucleus to the L1 segment followed a similar time course during development. The conduction time reached the adult value by P30, at which time the spinal cord is only half the adult length. 5. The conduction velocity between the C1 and L1 segments increased monotonically between E59 and P30, from a low of 1 m s-1 to a maximum of 34 m s-1. 6. The rise time of rubrospinal neuron somadendritic spikes followed a developmental time course similar to that for conduction time. 7. Myelination of rubrospinal axons, as judged by the presence of myelinated segment spikes, began to occur prior to E59. 8. These findings suggest that development of action potential propagation in rubrospinal cells can be divided into an early and a late stage: conduction time reaches the adult value during the early stage, i.e. by the first postnatal month, and is maintained during the late stage. We propose that myelination, axon diameter increase and maturation of membrane properties act to reduce conduction time to adult values during the early stage, while a proportional increase in fibre diameter with axonal length results in a constant conduction time during the late stage.

Action Potentials↗

Pain-related somatosensory evoked potentials following CO2 laser stimulation of foot in man.

Since our previous study of pain somatosensory evoked potentials (SEPs) following CO2 laser stimulation of the hand dorsum could not clarify whether the early cortical component N1 was generated from the primary somatosensory cortex (SI) or the secondary somatosensory cortex (SII) or both, the scalp topography of SEPs following CO2 laser stimulation of the foot dorsum was studied in 10 normal subjects and was compared with that of the hand pain SEPs and the conventional SEPs following electrical stimulation of the posterior tibial nerve recorded in 8 and 6 of the 10 subjects, respectively. Three components (N1, N2 and P2) were recorded for both foot and hand pain SEPs. N1 of the foot pain SEPs was maximal at the midline electrodes (Cz or CPz) in all data where that potential was recognized, but the potential field distribution was variable among subjects and even between two sides within the same subject. N1 of the hand pain SEPs was maximal at the contralateral central or midtemporal electrode. The scalp distribution of N2 and P2, however, was not different between the foot and hand pain SEPs. The mean peak latency of N1 following stimulation of foot and hand was found to be 191 msec and 150 msec, respectively, but there was no significant difference in the interpeak latency of N1-N2 between foot and hand stimulation. It is therefore concluded that N1 of the foot pain SEPs is generated mainly from the foot area of SI. The variable scalp distribution of the N1 component of the foot pain SEPs is likely due to an anatomical variability among subjects and even between sides.

Adult↗

Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of hypervariable region are indicative of poor response to interferon treatment in patients with chronic hepatitis type C.

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated with a poor response. Whereas all seven patients with group III genotype tested showed a good response (normalization of alanine aminotransferase level for more than 6 months), only 10 of 19 (53%) patients infected with group II genotype showed a good response. We also observed that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow viral decrease eventually showed a good response (p<0.04). None of the 26 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees of sequence variability were seen in three patients with group II hepatitis C virus who responded poorly to the therapy. All three showed slow decreases in virus titer during the first 2 weeks of treatment. In contrast, patients with genotype II who showed a good response to treatment were seen to have very few mutations. In three patients with genotype III who had responded well to interferon treatment, all showed very little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to interferon treatment. These data suggest that a slow decrease in virus titer during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with group II genotype, are associated with poor response to interferon treatment.

Adult↗

Maintenance of high virus load even after seroconversion in newborn cats acutely infected with feline immunodeficiency virus.

The viral loads in adult and newborn cats have been compared following injection with feline CD4+ FeL-039 line cells acutely infected with feline immunodeficiency virus (FIV). The level of virus genome in peripheral blood mononuclear cells (PBMC) increased progressively despite seroconversion in the newborn cats, whereas the virus genome was apparently cleared after seroconversion in the adult cats. Immunohistochemical staining of thymus of the FIV-infected newborn cats showed clusters of viral antigen-positive cells. These results indicate that FIV infection of the newborn cat results in higher virus loads than infection of the adult cat. We discuss these findings in relation to FIV as a model system for studies of the infection of neonates with an immunosuppressive retrovirus.

Acute Disease↗

Physiological study of cervical dystonia. Task-specific abnormality in contingent negative variation.

To investigate the pathophysiology of dystonia, we recorded contingent negative variation (CNV) in 12 patients with cervical dystonia and in 12 age-matched normal subjects. In a simple reaction time paradigm, the subjects were given a pair of a warning stimulus and a subsequent stimulus that triggered head rotation to either side or extension of the fingers. In normal subjects, CNVs for head rotation were not affected by neck muscle pre-activation simulating torticollis, and were always symmetrical with equally high amplitudes over the frontal and central leads. By contrast, CNVs for finger movement had the maximum over the central lead and showed a characteristic distribution; those for the right finger movement had the left hemisphere dominance, whereas those for the left finger movement had similar amplitudes over both hemispheres. In patients with rotatory torticollis (rotatocollis), the components of CNVs for head rotation were markedly attenuated in all the leads, except for the initial negative deflection (orienting response). As a whole, cervical dystonia patients had significantly lower amplitudes of late CNVs for head rotation than normal subjects (P < 0.001), whereas late CNV amplitudes in finger extension did not differ in the two groups. Their reaction times for head rotation were similar, but durations of EMG activities were prolonged in the patients because of co-contractions of the antagonists. The task-specific CNV amplitude loss is therefore not explained by reaction times or by the abnormal neck muscle activities prior to the movement, but it reflects a failure of neural activities preparing for a phasic neck movement, resulting in co-contraction of the agonists and the antagonist. Dystonia may be associated with defective retrieval or retaining of specific motor programmes or subroutines in response to sensory stimuli.

Adult↗

Three conserved glycine residues in valine activation of gramicidin S synthetase 2 from Bacillus brevis.

The translated product from the gene fragment containing the second and third domains of gramicidin S synthetase 2 was purified to an essentially homogeneous state. It showed valine- and ornithine-activating activity and the second domain was proved to be the valine-activating domain. Three mutant genes from Bacillus brevis Nagano, BI-3, E-4, and E-5 strains, which encode defective valine-activating domains of gramicidin S synthetase 2, were sequenced. By comparison with the wild-type gene, single point mutations of guanine to adenine were found at the three conserved glycine codons; the 5303rd guanine in BI-3, the 5378th guanine in E-4, and the 4967th guanine in E-5, which corresponded to codon changes of the 1768th glycine to glutamic acid and the 1793rd and the 1656th glycine to aspartic acid. Loss of valine-adenylation activity by mutation at the 1656th glycine proved the direct participation of the TSGT/STGXPKG motif in the adenylation reaction, and suggests that this glycine residue with the conserved lysine residue of the motif forms the phosphate-binding loop for ATP-binding. The 1793rd glycine is a member of the YGXTE motif which was also conserved among adenylate-forming enzymes except acetyl-CoA synthetases. The 1768th glycine residue appears to maintain the conformation of the active site for aminoacyl adenylation since this residue is retained among the adenylate-forming enzymes, though flanking regions are not conserved. These results suggest that these glycine residues are essential for adenylate formation in the antibiotic peptide synthetase family and some other adenylate-forming enzymes.

Amino Acid Isomerases↗

Endothelium-dependent contraction in intrapulmonary arteries: mediation by endothelial NK1 receptors and TXA2.

1. We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium-dependent contraction (EDC) in the rabbit isolated intrapulmonary artery. 2. Removal of the endothelium almost abolished the contraction induced by SP (10(-8) M) while it did not attenuate the contraction induced by SP (10(-7) M), NKA (10(-9) - 10(-7) M) or NKB (10(-8) and 10(-7) M). 3. The EDC induced by SP (10(-8) M) was abolished by NK1 antagonists (FK-888, CP-96345, CP-99994 and SR-140333) but not by an NK2 antagonist (SR-48968). 4. The EDC induced by SP was attenuated by cyclo-oxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-046, KY-234 and KY-063) and a TXA2 antagonist (S-1452). 5. The rank order of potency causing endothelium-independent contraction (EIC) was NKA > NKB > SP. The EIC induced by SP (10(-7) M) was attenuated by an NK2 antagonist but not by NK1 antagonists, cyclo-oxygenase inhibitors, TXA2 synthetase inhibitors or a TXA2 antagonist. 6. In conclusion, SP at 10(-8) M induces EDC via endothelial NK1 receptors and TXA2 production, and SP at 10(-7) M induces EIC via NK2 receptors in the rabbit intrapulmonary artery.

Animals↗

Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity: synthesis and evaluation of a new series of indole derivatives.

A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives were prepared and evaluated for thromboxane A2 (TXA2) synthetase-inhibitory and histaminergic H1-blocking activity. Among the compounds synthesized, indole-6-carboxylic acid derivatives showed higher activities than the other positional isomers of carboxylic acid. 1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )-1H-indole-6-carboxylic acid (12) had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8) M) and H1-blocking activity (IC50 = 8 x 10(-9) M).

Animals↗

Early embryonic development in vitro and embryo transfer in the cat.

Ten female cats were given a total dose of 200 IU PMSG over 3 days to induce superovulation. One to four-cell stage embryos were collected by flushing the oviducts 48 to 54 hr after the initial 250 IU dose of hCG. Some of the normal embryos collected were examined for culture in Medium-199 supplemented with 20% FCS. After 72 hr of culture, 222/248 (89.5%) had developed to the morula stage, and by 96-168 hr, 110 (64.7%) out of 170 morulae had developed into blastocysts. Four to 12 embryos cultured in vitro per cat were transferred to one of the uterine horns of 12 recipients in which synchronous ovulation had been induced with hCG. All 4 recipients of embryos which had developed to the morula stage on culture day 3, 3 of the 5 recipients of blastocysts on culture days 4-6, and none of the 3 recipients of blastocysts on culture day 7 became pregnant. It is concluded that early feline embryos are capable of efficiently developing into transferable morulae in vitro by ordinary culture methods, but that there is partial developmental arrest from the morula to the blastocyst stage.

Animals↗

Purification and properties of branched chain amino acid aminotransferase from gramicidin S-producing Bacillus brevis.

The branched chain amino acid aminotransferase [EC 2.6.1.42] was purified to a homogeneous state from a gramicidin S-producing strain of Bacillus brevis. The enzyme had a molecular weight of about 93,000 and consisted of two identical subunits, each with a molecular weight of about 47,000. One pyridoxal phosphate is bound per subunit. In addition to branched chain amino acids, the enzyme uses L-phenylalanine and L-tryptophan as the amino donor, indicating that B. brevis branched chain amino acid aminotransferase has a broad substrate specificity for the amino donor. The enzyme utilized 2-oxoglutarate as the amino acceptor. The purified enzyme exhibits its absorption maxima at 332 and 427 nm at neutral pH.

Bacillus↗