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Biomedical subjects

M Kunimoto

Publications and source records attributed to M Kunimoto.

At least 73 records · Page 4Linked to original sources

Neuro-effector characteristics of sweat glands in the human hand activated by irregular stimuli.

Intraneural electrical stimulation of cutaneous fascicles in the median nerve was performed in 24 normal subjects and the effects on sweating within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (wvpp). The aims were: (1) to investigate the response variability between repeated stimulation sequences in the same skin site and between different sites and (2) to compare quantitative effects of regular and irregular stimulation on skin resistance and wvpp. Regional axillary anaesthesia of the brachial plexus eliminated spontaneous and reflex sympathetic activity. With repeated irregular stimulation sequences skin resistance responses from the same skin site varied only slightly between trials. Differences between response curves from two skin sites in the same subject or from different subjects were also small but significantly greater (P < 0.01) than differences between responses to repeated stimulation in the same site. Irregular stimulation with average frequencies of 0.49 Hz and 3.51 Hz gave greater resistance responses than if the same number of stimuli were delivered regularly (P < 0.01). The difference was most pronounced at 0.49 Hz. At an average frequency of 0.49 Hz the stimulation usually evoked no changes of wvpp whereas an average frequency of 3.51 Hz caused an increase of wvpp which was greater with irregular than with regular stimulation in all subjects. We conclude that: (1) sweat responses to sudomotor nerve traffic vary slightly due to local factors in the skin or the terminal nerve endings and (2) irregular sudomotor nerve traffic evokes more sweat than if the same impulses occur regularly.

Adult↗

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.

Adult↗

[A case of transfusion-associated GVHD after total laryngectomy].

We report a case of fatal transfusion-associated graft versus host disease (GVHD) that developed in a patient with laryngeal cancer. After a 39.6Gy irradiation dose, total laryngectomy with right radical neck dissection was performed. The postoperative course was uneventful. However, seven days after blood transfusion, high fever (38.5 degrees C) suddenly appeared. On the ninth day, watery diarrhea and facial erythema were observed. On the 12th day, liver disturbance and pancytopenia developed. The patient died on the 16th day because of overwhelming sepsis. Transfusion-associated GVHD has a mortality rate of more than 90%. Therefore, the most important procedure for preventing GVHD is the use of irradiated blood products. Furthermore unnecessary blood transfusion should be avoided.

Graft vs Host Disease↗

Diagnosis of aneurysm of superior thyroid artery by CT and MR imaging.

A 51-year-old man presented with a nonpulsatile anterior neck mass which suggested a thyroglossal duct cyst. At CT a small cystic mass was revealed. The mass contained a well-defined, crescent-shaped, low-density area with homogeneous contrast enhancement. On MR T2-weighted spin-echo and gradient-echo images the mass was as hyperintense as the neck vessels. Angiography and operation confirmed an aneurysm of the left superior thyroid artery with a mural thrombus.

Aneurysm↗

[A ruptured aneurysm at the peripheral collateral circulation of the anterior choroidal artery in a patient with moyamoya disease: a case report].

This 42-year-old man experienced a sudden onset of occipital headache. Neurological examination revealed a moderately disturbed consciousness and a moderate left hemiparesis. CT scan disclosed a hugh hematoma in the right temporo parietal lobe without intraventricular hemorrhage. A cerebral angiography demonstrated typical findings of moyamoya disease and a small saccular aneurysm at the peripheral portion of the right anterior choroidal artery, which was dilated at the collateral circulation to the parietal lobe. The hematoma was removed at once by a craniotomy. He became alert but mild hemiparesis persisted. MRI disclosed a small signal-void lesion lateral to the trigone of the right lateral ventricle. The angiography repeated three weeks after the removal of the hematoma showed the unchanged size of the aneurysm. Direct surgery for the aneurysm was performed via the right parietal transcortical approach. The aneurysm was reached under the guidance of the intraoperative angiography. Trapping of the parent artery and the excision of the aneurysm were performed. On the basis of the presence of an internal elastic lamina at the neck of the aneurysm, the surgical specimen was histologically verified to be a true aneurysm. Since the collateral circulation was well preserved during surgery, no worsening of the neurological manifestation was observed. In view of the unfavorable prognosis for a moyamoya patient with this type of the aneurysm, which often results in a massive ventricular or intracerebral hemorrhage, surgery directed to the aneurysm itself should be considered.

Adult↗

[A septated syringomyelia with a dramatic clinical course in a young patient with MELAS; a case report].

This is a report of a young girl who showed a recurrence of acute worsening and remission of neurological manifestations, with consistent MRI demonstration of transaxial septated syrinxes in the cervical and the lumbar spinal cord in addition to a tight filum terminale. This 8 year-old girl had developed normally since her birth until August 1989 when she developed a gait disturbance. This worsened acutely on January 1, 1990, with the additional manifestation of a urinary bladder disturbance. General examination failed to show any abnormality or scoliosis. Neurologic examination revealed a monoparesis of the right lower extremity with muscle atrophy and pyramidal tract sign. Fecal constipation and urinary retention were noted. The MRI T1 weighted sagittal image demonstrated an incontinuous low intensity signal in the C1-C7 as well as in the T12-L2 without swelling of the cord. The axial image clearly demonstrated the septations in the syrinx which looked like eye glasses. No definite Gd enhancement was demonstrated. Chiari malformation was not associated, but the tethered cord was well identified. With the administration of steroid, she showed a marked improvement of neurological manifestations. She was able to urinate without difficulty and also walk by herself. For one month thereafter she remained well with minor neurological deficits until she developed a worsening of the gait disturbance with a newly manifested weakness of the left upper extremity. Sensory impairment was also demonstrated below L3. In contrast to the worsening of the clinical symptoms, no definite change in the abnormalities found by MRI was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗

In vivo benzodiazepine receptor occupancy by CL 218,872 visualized by positron emission tomography in the brain of the living baboon: modulation by GABAergic transmission and relation with anticonvulsant activity.

In vivo benzodiazepine receptor occupancy by increasing doses of CL 218,872 has been evaluated in the baboon Papio papio, using (11C) RO 15-1788 as specific radioligand and positron emission tomography as external detection system. Although BZR heterogeneity has been previously demonstrated in the brain of the living baboon using PET, we did not observe in our studies that CL 218,872 interacts preferentially with one of the BZR subtypes. The monophasic pattern of the dose dependent CL 218,872 displacement curve and the corresponding "in vivo Hill coefficient" near unity suggest that CL 218,872 binds in cerebral baboon cortex with a similar affinity with BZ1 as well as BZ2 subtypes. The anticonvulsant properties of CL 218,872 against bicuculline and allylglycine-induced seizures were correlated with benzodiazepine receptor occupancy by assessment of electroencephalographic activity during positron emission tomography studies. Our data confirmed in vivo the hypothesis of a partial agonist anticonvulsant activity of CL 218,872. At the same time, the use of a GABA-antagonist (bicuculline) or an inhibitor of the GABA synthesis (allylglycine) suggested the existence of an allosteric interaction between benzodiazepine receptors and GABA receptors.

Allylglycine↗

Isolation and characterization of cDNAs encoding human brain ankyrins reveal a family of alternatively spliced genes.

Ankyrins are a family of membrane-associated proteins that can be divided into two immunologically distinct groups: (a) erythrocyte-related isoforms (ankyrinR) that have polarized distributions in particular cell types; and (b) brain-related isoforms (ankyrinB) that display a broader distribution. In this paper, we report the isolation and sequences of cDNAs related to two ankyrinB isoforms, human brain ankyrin 1 and 2, and show that these isoforms are produced from alternatively spliced mRNAs of a single gene. Human brain ankyrin 1 and 2 share a common NH2-terminus that is similar to human erythrocyte ankyrins, with the most striking conservation occurring between areas composed of a repeated 33-amino acid motif and between areas corresponding to the central portion of the spectrin-binding domain. In contrast, COOH-terminal sequences of brain ankyrin 1 and 2 are distinct from one another and from human erythrocyte ankyrins, and thus are candidates to mediate protein interactions that distinguish these isoforms. The brain ankyrin 2 cDNA sequence includes a stop codon and encodes a polypeptide with a predicted molecular mass of 202 kD, which is similar to the Mr of the major form of ankyrin in adult bovine brain membranes. Moreover, an antibody raised against the conserved NH2-terminal domain of brain ankyrin cross-reacts with a single Mr = 220 kD polypeptide in adult human brain. These results strongly suggest that the amino acid sequence of brain ankyrin 2 determined in this report represents the complete coding sequence of the major form of ankyrin in adult human brain. In contrast, the brain ankyrin 1 cDNAs encode only part of a larger isoform. An immunoreactive polypeptide of Mr = 440 kD, which is evident in brain tissue of young rats, is a candidate to be encoded by brain ankyrin 1 mRNA. The COOH-terminal portion of brain ankyrin 1 includes 15 contiguous copies of a novel 12-amino acid repeat. Analysis of DNA from a panel of human/rodent cell hybrids linked this human brain ankyrin gene to chromosome 4. This result, coupled with previous reports assigning the human erythrocyte ankyrin gene to chromosome 8, demonstrates that human brain and erythrocyte ankyrins are encoded by distinct members of a multigene family.

Amino Acid Sequence↗

A new 440-kD isoform is the major ankyrin in neonatal rat brain.

This report describes initial characterization of a 440-kD isoform of brain ankyrin (ankyrinB) representing an alternatively spliced mRNA product of the gene encoding the major isoform of ankyrin in adult human brain (Otto, E., M. Kunimoto, T. McLaughlin, V. Bennett, J. Cell Biology. 114:241-253). Northern and immunoblot analyses indicate that 440-kD ankyrinB includes the spectrin and membrane-binding domains as well as a regulatory domain of the major 220-kD isoform. 440-kD ankyrinB contains, in addition, a sequence of a predicted size of 220 kD which is inserted between the regulatory domain and spectrin/membrane-binding domains. 440-kD ankyrinB has properties expected of a peripherally associated membrane-skeletal protein: it is exclusively present in the particulate fraction of brain homogenates, is extracted with NaOH, and remains associated with Triton-X-100-resistant structures. Expression of 440-kD ankyrinB in rat brain began at birth before other ankyrins could be detected, peaked 10 d after birth, and then decreased progressively to 30% of the maximum in adults. Expression of the 220-kD ankyrinB and ankyrinR (erythroid ankyrin) began approximately 10 d after the 440-kD isoform, increased rapidly between 10 and 15 d after birth, and finally achieved their maximal levels in adults. 440-kD ankyrinB is present in approximately equivalent amounts in all regions of neonatal brain while in adult brain it is present in highest levels in cerebellum and lowest in brain stem. 440-kD ankyrinB was localized by immunofluorescence in regions of neonatal and adult brain containing primarily dendrites and unmyelinated axons. 440-kD ankyrinB thus may play a specialized role in neuronal processes.

Animals↗

Neuroeffector characteristics of sweat glands in the human hand activated by regular neural stimuli.

1. Intraneural electrical stimuli (0.3-1.2 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in twenty-eight normal subjects. The effects on sweat glands within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (WVPP). Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. 2. At stimulation frequencies of 0.1 Hz each stimulus evoked a transient skin resistance reduction, the amplitude of which varied initially but reached a steady state of less than 10 k omega after, on average, nine responses. If preceded by stimulation-free intervals of 5 min or more, up to fifteen stimuli were required before the first response occurred. With higher frequencies individual responses started to merge, skin resistance levels decreased successively and levelled off around 10 Hz. The total change of resistance (0-10 Hz) was 101 +/- 46 (n = 9) k omega and the higher the pre-stimulus level, the larger the reduction (r = 0.68, P less than 0.05). 3. Stimulus-response latencies to the onset of a skin resistance reduction (single stimuli or trains of six impulses/20 Hz given at 0.1 Hz) shortened initially but reached steady-state values after on average nine to twelve impulses. Average conduction velocity between stimulating electrode and skin resistance recording site was 0.78 m/s and average time for electrical neuroeffector transfer in sweat glands was estimated to be 348 ms. 4. In addition to direct stimulation-induced resistance responses there were also small spontaneous reductions of resistance. They were seen in all subjects and at all frequencies but were more common in some subjects and occurred predominantly at the beginning of stimulation or at changes of frequency. They occurred independently at two skin sites in the same subject and disappeared during stimulation-free periods and after atropine. 5. With train stimulation (six impulses/20 Hz) at 0.1 Hz, each train evoked transient increases of WVPP of 1 mmHg or less in some subjects (latency around 1.6 s). After averaging weak increases were seen also after single stimuli in two subjects. Increases of stimulation current or frequency led to slowly developing sustained increases of WVPP concomitant with decreases in skin resistance. 6. Responses in skin resistance and WVPP to train stimulation at 0.1 Hz were suppressed in a dose-dependent way by I.V. injections of atropine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[The localization and production of interleukin-1 in pharyngeal epithelium].

Interleukin-1 (IL-1) has been thought to be one of the essential cytokines mainly produced by macrophage. The function of IL-1 are not only activates T-lymphocytes, but also regulates immune responses to several antigens and effects on local and systemic immune reactions. Recently, it is reported that epidermal keratinocytes produces IL-1, and attention has been paid to local immune reaction mediated with this cytokine. In this study, we performed immunohistochemistry and immunoblotting on the pharyngeal epithelial keratinocytes and we evaluated the production of IL-1 by these cells. Pharyngeal mucous membrane of each region reacted strongly against anti-IL-1 alpha antibody, on the contrary, anti-IL-1 beta antibody comparatively only weakly. Strong reactivity was often observed on the basal layer, then it was seemed that some important relationship exists between the production of IL-1 and maturation of pharyngeal keratinocytes. Infiltration of T-lymphocytes was observed in proportion to the increase of epithelial reactivity against IL-1. There seemed to be no correlation between expression of HLA-DR antigen on keratinocytes and reactivity of IL-1. In immunoblotting study, the 31kD band, intracellular immature molecule, was identified besides 17 and 52kD. From this finding, it was suggested that IL-1 is derived from pharyngeal keratinocytes. In conclusion, the present study is helpful for well-understanding of local cellular immunity of pharyngeal mucous membrane.

Adult↗

[X-ray CT of Duchenne muscular dystrophy skeletal muscles--chronological study for five years].

To clarify when and how rapidly individual muscles are damaged in the course of Duchenne muscular dystrophy (DMD), we followed X-ray CT of whole body skeletal muscles from 29 cases of DMD patients (age ranging 3 to 23 years) for a period of 2 to 6 years. Each patient had 2 to 5 scans with an average of 3.3. We evaluated chronological changes of 23 muscles from the entire body using the muscle damage stage defined as follows. The stages were classified into the following 5 stages: stage 0; normal, 1; area of fatty replacement less than 10% of whole muscle area, 2; area of fatty replacement between 10 to 50%, 3; area of fatty replacement 50 to 90%, 4; almost complete fatty replacement. Each muscle had its own period of rapid degeneration starting at 5 to 10 years of age and, continuing 5 to 10 years. In some muscles such as gluteus maximus or quadriceps femoris, fatty replacement started at 5 years or earlier and progressed for five years, while other muscles such as splenius capitis, damage started much later, e.g. around 10 years of age and the progression was much slower. There was a variation of at least 5 years among individual patients in any muscle damage stage, reflecting the variability of clinical severity in each patient. On the basis of the above results we defined the whole body muscle damage index as a summation of the muscle damage stages of the following five muscles: gluteus maximus, quadriceps femoris, gracilis, medial head of gastrocnemius and splenius capitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Can galvanic skin response be used as a quantitative estimate of sympathetic nerve activity in regional anesthesia?

To study the relationship between skin sympathetic nerve activity and changes in skin resistance (galvanic skin response--GSR), efferent sympathetic and sensory nerves to the hand were blocked by an axillary nerve blockade in 15 healthy subjects. Subsequently, intraneural electrical stimuli in the median nerve distal to the axillary nerve block were used to evoke changes in skin resistance and in water vapor partial pressure in the sensory and sympathetically denervated hand. With increasing frequency of stimulation, skin resistance decreased and water vapor partial pressure increased until stimuli exceeded 10 Hz. When an additional burst of impulses was added to the background stimulation, GSR amplitude varied in a nonlinear fashion with the background frequency. Stimulation-induced GSR was completely abolished in a dose-dependent manner by systemically (intravenously) administered atropine. The results indicate that GSR depends on the preceding level of nerve traffic in the sympathetic sudomotor nerve fibers. Consequently, skin resistance recordings cannot be used to quantify sympathetic nerve traffic and thus do not express the completeness of sympathetic blockade in regional anesthesia.

Adult↗

Interaction of suriclone with central type benzodiazepine receptors in living baboons.

The interaction of suriclone and two of its main metabolites with central type benzodiazepine receptors, which had been labeled in vivo with the radioligand [11C]RO 15-1788, was investigated in living baboons. The concentration of radioligand bound to the receptors, as measured in brain transverse sections by positron emission tomography, decreased rapidly after the i.v. administration of suriclone at doses known to induce pharmacological effects. The rate and extent to which [11C]RO 15-1788 binding was displaced increased with increasing doses of suriclone. The half-inhibitory dose (ID50) was determined to be 0.08 mg/kg in vivo. The rapid inhibitory effect of suriclone on the in vivo binding of [11C]RO 15-1788 in the brain seems to reflect its ability to act at the GABA-benzodiazepine receptor complex, at or near to the benzodiazepine binding site, to induce its pharmacological activity. The i.v. injection of the demethylated metabolite of suriclone, RP 35,489, only caused a slight displacement of [11C]RO 15-1788 binding even at a dose of 2 mg/kg. Thus, suriclone appears to be more potent than RP 35,489 to displace the benzodiazepine 11C antagonist in vivo. The sulfoxide metabolite, RP 46,166, did not significantly change the kinetics of [11C]RO 15-1788 binding in the brain. The slight effects produced by high doses of RP 35,489 and RP 46,166 on [11C]RO 15-1788 binding in the brain suggest that these metabolites are probably not responsible for the expression of biological activity of suriclone mediated by benzodiazepine receptors.

Animals↗