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Biomedical subjects

M Tsukaguchi

Publications and source records attributed to M Tsukaguchi.

At least 19 recordsLinked to original sources

The validity of a hyperventilation test for an investigation of autonomic failure: assessment in patients with multiple system atrophy and Parkinson's disease.

Although heart rate (HR) responses to hyperventilation (HV) have been used as a cardiovascular autonomic function test, autonomic involvement during HV remains uncertain. To clarify the relationship between autonomic activity and cardiovascular changes during HV, we compared cardiovascular responses during HV among subjects with different autonomic function, namely 16 patients with probable multiple system atrophy (MSA), 16 with possible MSA, 28 with Parkinson's disease (PD) and 28 healthy controls. Abnormalities of cardiovascular responses to head-up postural change and the Valsalva maneuver were definitely present in the order of probable MSA, possible MSA and PD, and abnormal HR and blood pressure (BP) responses during HV were observed in probable MSA and possible MSA, but not in PD. Unlike the significant difference in standard cardiovascular autonomic function tests, the HR and BP responses during HV were equivalent between probable and possible MSA. These findings suggest that cardiovascular control during HV may be affected not only by autonomic activity but also by other factors.

Adult↗

Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies.

The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.

Antibody Formation↗

Abnormal baroreceptor-mediated vasopressin release as possible marker in early diagnosis of multiple system atrophy.

BACKGROUND: Although autonomic failure (AF) is a critical symptom of multiple system atrophy (MSA), it may not appear until late in the disease process. OBJECTIVES: To clarify whether a detailed investigation of the autonomic nervous system in patients with MSA without overt AF demonstrates latent lesions of central cardiovascular control circuits and facilitates the early diagnosis of MSA. METHODS: Autonomic function tests, and plasma noradrenaline (NA) and vasopressin (AVP) responses to head-up tilt (HUT), were studied in 12 patients with MSA with AF (probable MSA), 12 with MSA without overt AF (possible MSA), and 24 controls. RESULTS: Abnormalities of cardiovascular autonomic function tests were prominent in the first group but mild in the second. Plasma NA and AVP increments upon HUT differed significantly among all three groups. CONCLUSIONS: These results indicate that probable MSA involves diffuse degeneration of central cardiovascular control circuits. On the other hand, the discrepancies in possible MSA suggest a vulnerability of the noradrenergic (A1) neurones of the caudal ventrolateral medulla that are involved in AVP secretion. This finding also suggests that AVP increment may be useful as a diagnostic tool in the early stages of MSA.

Aged↗

Impaired novelty P3 potentials in multiple system atrophy--correlation with orthostatic hypotension.

Although neuropsychological tests demonstrate frontal lobe dysfunction in multiple system atrophy (MSA), assessment of frontal function using event-related brain potentials (ERPs) has not been sufficiently performed in MSA. The correlation between frontal lobe dysfunction and orthostatic hypotension (OH), which is known to cause frontal hypoperfusion, remains unclear. Our objectives were to assess frontal lobe dysfunction in MSA patients using ERPs and to elucidate the relevance of OH to changes in ERPs. Nine consecutive patients with MSA and nine age- and gender-matched healthy controls were compared by performance in the Wisconsin Card Sorting Test (WCST) and somatosensory ERPs to target and novel stimuli, namely, parietal maximal P3 (target P3) and fronto-central P3 (novelty P3), respectively. The correlation between novelty P3 and OH was evaluated in the MSA group. The MSA group showed a poorer performance in categories achieved (CA), total errors (TE) and perseverative errors by Nelson's (PEN) method in the WCST compared with the control group (CA and PEN: p<0.01; TE: p<0.02). Novelty and target P3s in the MSA group showed significantly prolonged latency (novelty: p<0.05; target: p<0.01) and reduced amplitude (novelty: p<0.02; target: p<0.01) compared with the control group. There was a significant negative correlation between novelty P3 latency and a drop in systolic blood pressure (r=0.76; p<0.02). Abnormalities of novelty P3 in the MSA group might reflect frontal lobe dysfunction, namely failure of attentional set-shifting, that was identified by the WCST. OH may play a role in the development of frontal lobe dysfunction in MSA.

Adult↗

Reduction in terminal excitability of nigrostriatal dopaminergic neurons in rats following chronic L-dopa administration.

The effects of chronic L-dopa administration on antidromic excitability and the firing rate of nigrostriatal dopaminergic neurons were investigated in urethane-anesthetized rats. Rats that received daily L-dopa (100 mg/kg) and carbidopa (25 mg/kg) for 60 days showed a marked decrease in terminal excitability compared with the controls. There were no significant differences in the firing rates between the two groups. This finding may be related to impaired striatal dopamine release from exogenous L-dopa subsequent to chronic L-dopa treatment.

Animals↗

[Low-dose oral etoposide and subcutaneous injection of low-dose cytosine arabinoside (Et-A non i.v.) with or without minimum anthracycline for refractory acute non-lymphoblastic leukemia].

Low-dose oral etoposide (50 mg for 10 to 14 days) and low-dose subcutaneous injection of cytosine arabinoside (15-20 mg/12 hours for 14 to 17 days) (Et-A non i.v.) were given to refractory acute non-lymphoblastic leukemia patients. Case 1 was a 47-year-old woman who had a relapsed M0. B-DOMP therapy failed but she recovered from severe infection. She had to go home to take care of her children. Et-A non i.v. was given for 14 days and 11 mg of mitoxantrone was added on the 3rd day. She achieved a complete remission (CR). Case 2 was a 72-year-old woman classified M4. Low-dose cytosine arabinoside (Ara-C) with additional daunorubicin (DNR) therapy failed. She became weaker due to the gastrointestinal toxicity of DNR. Et-A non i.v. was tried. Oral etoposide (Et) for 10 days and Ara-C for 14 days proved effective, and she achieved CR. Case 3 was a 59-year-old man with M4 developed from myelodysplastic syndrome, complicated with infection. Ara-C low-dose therapy was begun, but it was not effective. It was switched to Et-A non i.v., 40 mg of DNR was added, with 12 mg of mitoxantrone and double administration of 3 mg of vindesine. He also achieved CR. Et-A non i.v. therapy is effective and available for induction therapy with low toxicity and convenient to daily life.

Aged↗

["Painful legs and moving toes" and muscle cramps spreading to the bilateral legs in a patient with alcoholic polyneuropathy].

A 37-year-old man with alcoholic polyneuropathy showed involuntary movement as intermittent flexion-extension or abduction-adduction of his toes identical to "painful legs and moving toes (PLMT)" and muscle cramps. Regarding the sequential spreading of PLMT and cramps from unilateral to contralateral leg muscles and phasic discharges observed by a needle EMG in the foot muscles during PLMT, we suppose that a spinal or supraspinal mechanism was responsible for the production of those movements. This case showed novel aspects of PLMT which was induced by sensory stimulation of the left lower leg and subsequently initiated cramps. The destruction of the lumbar sympathetic ganglion remarkably ameliorated the spontaneous PLMT and cramps, whereas sensory stimulation of the left lower leg still induced those movements. Therefore, we think that sensory inputs from peripheral nerves played a critical role in the generation of PLMT and cramps, and abnormal activities of spinal sympathetic nerves exacerbated those involuntary movements. Sensory induced PLMT may be a subgroup of this movement disorder.

Adult↗

Efficacy of doramectin against intestinal nematodes and sarcoptic manage mites in naturally infected swine.

Endectocidal efficacy of doramectin administered intramuscularly at a dosage of 300 micrograms/kg was evaluated in 464 pigs naturally infected with intestinal nematodes or mange mites on 14 commercial farms in Japan. By doramectin treatment, fecal egg counts were reduced > 99% for Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, and Trichuris suis; worm counts of T. suis and mite counts of Sarcoptes scabiei reduced 90.1% on Day 21 and 99.5% on Day 28 following treatment, respectively.

Animals↗

[A case of chronic inflammatory demyelinating neuropathy associated with antibodies to gangliosides GM1 and GalNAc-GD1a].

In January 1993, a 43-year-old man was admitted to our hospital for left wrist-drop. Neurological examinations revealed asymmetrical distal weakness in the upper limbs. Deep tendon reflexes were normal in all 4 limbs. Sensory and autonomic nervous functions were intact. CSF examinations were within normal limits. Thin-layer chromatography with immunostaining revealed serum antibodies that reacted with GM1 and GalNAc-GD1a. Motor nerve conduction studies revealed abnormal temporal dispersion, and a low amplitude of compound muscle action potential in the left radial nerve. Neurological symptoms gradually improved with prednisolone over one and a half years. He was hospitalized again in January 1995, because of right wrist-drop and slight sensory loss of the limbs. Those findings were improved by methylprednisolone (1,000 mg/day) for 3 days. The interval until maximal disability in this patient was more than one month for each admission. This case must belong to inflammatory demyelinating neuropathy.

Acetylgalactosamine↗

Significance of cognitive function in the elicitation of sympathetic skin response in healthy humans.

The sympathetic skin response (SSR) is used as an index of sudomotor sympathetic function. However, the central processing of this response is not fully understood. To clarify this point, we assessed the relevance of cognitive function in the elicitation of SSR in 14 healthy subjects by recording simultaneously the somatosensory event-related potential (ERP) and SSR evoked by electric stimuli. The ERP paradigm consisted of three types of stimuli, task-relevant target, task-irrelevant electric shock which is equivalent to the common stimulus for eliciting SSR, and task-irrelevant standard stimuli. ERPs were recorded at Fz, Cz, and Pz on the scalp, SSRs were recorded in both palms and soles of the subject after each stimulus in the ERP paradigm. Target stimuli generated a P300 (P3b) and elicited a variety of SSRs from subject to subject. Electric shock stimuli generated a novelty P300 with a shorter peak latency and a higher amplitude than the P3b, with stable elicitation of SSR in the four limbs of all subjects. P300 amplitude showed a significant positive correlation with SSR amplitude with electric shock stimuli. This correlation predominated in the frontal region (Fz), as compared with the parietal region (Pz). A negative correlation between P300 latency and SSR amplitude with electric shock stimuli was also observed. These findings indicate that the elicitation of SSR is influenced by the generation of novelty P300, that is, cognitive function. The frontal region may play a key role in the elicitation of SSR. We believe that the assessment of novelty P300 is required for a precise interpretation of the SSR.

Adult↗

[Non-paralytic pontine exotropia with alternating exotropia].

We report a patient with pontine infarction who showed non-paralytic pontine exotropia (NPPE) with alternating exotropia. An 81-year old woman developed diplopia and gait disturbance. On the fourth day, she was admitted to our hospital. Oculomotor findings on admission showed that the ocular position of the left eye on forward gaze was fixed at the midline, while the right eye was abducted. When she was instructed to use the right eye for forward gaze, the left eye deviated outward. On right gaze, the left eye was not abducted and monocular nystagmus was noted in the abducted right eye. Upper gaze was limited in the right eye and convergence was not possible. The remaining ocular movements were intact. On cranial CT performed on eye closure, the left eye was abducted and the right eye was fixed at the midline. Brain MRI showed cerebral infarction located in the left paramedian portion of the middle pontine tegmentum with involvement of the medial longitudinum fasciculus (MLF) and in the ventral site of the upper pons. On the 16th day, right exotropia disappeared on eye opening without forward gaze, but forward gaze easily induced outward deviation of the right eye. On the 39th day, right exotropia on forward gaze had almost disappeared. However, left MLF syndrome and abnormal convergence were persistent when she discharged on the 76th day. In conjunction with oculomotor and neuroradiological findings, the NPPE with alternating exotropia in our patient may be due to severe MLF damage and secondary hyperactivity of the contralateral paramedian pontine reticular formation.

Aged↗

[A case of mitochondrial encephalomyopathy with peripheral neuropathy and autonomic symptoms].

We report a 28-year-old man with mitochondrial encephalomyopathy with peripheral neuropathy and autonomic symptoms. Muscle biopsy from the quadriceps femoris muscle showed myopathic changes with ragged-red fibers and abnormal mitochondria. He experienced recurrent and acute weakness in his bilateral lower limbs. Needle electromyogram revealed neurogenic changes, and the amplitude of muscle action potential was low in the right posterior tibial nerve. Sural nerve biopsy showed a marked loss of both large and small myelinated fibers, and moderate to severe axonal degeneration was diagnosed. He experienced autonomic symptoms (nausea, constipation, hypoidosis and urinary retention) along with the weakness in his lower limbs which is considered to be a very rare situation. We hypothesized that autonomic symptoms in this case were due to the axonal degeneration that included unmyelinated fibers.

Action Potentials↗

[A case of facial diplegia in associated with reactivation of herpes simplex virus type I].

A 27-year-old Japanese man developed right peripheral facial palsy after suffering from a cold and low-grade fever for 7 days. Left peripheral palsy developed 4 days later. When he visited our hospital 3 days after that, neurological examination revealed no abnormalities except peripheral facial diplegia. Cerebrospinal fluid (CSF) was normal on admission and on hospital day 12. On admission, the patient had a transient increase of serum titers of HSV type I IgM (fluorescence assay). Then, serum titers of HSV type I IgG (ELISA) continuously increased. A diagnosis of peripheral facial diplegia due to reactivation of HSV type I was made clinically and serologically. Steroid pulse therapy was performed and his facial diplegia disappeared completely after 2 weeks. This case may support the hypothesis of virus etiology of Bell's palsy, and HSV type I should be considered as one of the possible causes of facial diplegia.

Adult↗

Distinct kinetics of subunit autolysis in mammalian m-calpain activation.

Subunit autolysis of mammalian m-calpain upon activation was examined in kinetic terms using a set of antibodies recognizing different portions of the protease. Activation of m-calpain by calcium resulted in no apparent autolysis in the large catalytic subunit, whereas the small regulatory subunit underwent immediate autolysis followed by substrate proteolysis. This profile of subunit autolysis is distinct from that of the other ubiquitous isozyme, mu-calpain, in which autolysis of the large subunit and then of the small subunit precedes substrate proteolysis under the normal conditions. The activation state of m-calpain thus is not reflected by the large subunit autolysis. The mode and role of autolysis may vary among calpain isozymes.

Amino Acid Sequence↗

Transplantation of allogeneic peripheral blood stem cells after myeloablative treatment of a patient in blastic crisis of chronic myelocytic leukemia.

A 48-year-old man in blastic crisis of chronic myelocytic leukemia received a transplant of allogeneic peripheral blood stem cells. The donor was his HLA-identical sister, who refused to donate bone marrow cells, but agreed to donate peripheral blood stem cells. The patient received standard transplant conditioning with cyclophosphamide (120 mg/kg) and busulfan (16 mg/kg). Peripheral blood stem cells were mobilized with granulocyte colony stimulating factor and collected by apheresis. After transplantation, the white blood cell count and the result of microscopic analysis of the bone marrow became normal, and the leukocyte karyotype became 46XX. DNA fingerprinting showed complete chimerism. Graft-versus-host disease was suppressed with cyclosporine and methyl-prednisolone. The patient died of recurrence of leukemia on day 102+.

Blast Crisis↗