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Biomedical subjects

T Mizutani

Publications and source records attributed to T Mizutani.

At least 73 records · Page 4Linked to original sources
PubMed2001

Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus.

Mechanisms of anti-hantaviral activities of bovine lactoferrin (LF) and ribavirin (Rbv) were investigated. Hantavirus focus formation at 48 hr was 15% of the control in cells treated with 400 microg/ml LF for 1 hr at 37 degrees C prior to viral infection. Post infection treatment with 100 microg/ml Rbv also inhibited the focus formation to 2.5% of the control. Combined LF pre- and Rbv post-infection treatment completely inhibited focus formation. Viral glycoprotein (G2) and nucleocapsid protein (NP) syntheses were delayed in LF pretreated cells up to 24 hr post infection (hpi) but became comparable to the control by 48 hpi. Further, LF inhibited viral shedding at 24 hpi but did not inhibit shedding after 48 hpi. However, Rbv was able to inhibit synthesis of viral proteins, (+) and (-) strand RNAs also inhibited viral shedding after 24 hr. These results suggest that LF inhibits viral adsorption to cells, while Rbv inhibits viral RNA synthesis. For in vivo trials of LF and Rbv, LF pre- and Rbv post-treatment were evaluated in suckling mice infected with hantavirus, of which 7% survived. LF concentrations of 40 and 160 mg/kg administered prior to viral challenge improved survival rates to 15% and 70%, respectively for single administration and 85% and 94%, respectively, for double administration. Rbv concentrations of 25 and 50 mg/kg gave survival rates of 68% and 81%, respectively. This suggests that both LF and Rbv are efficacious in hantavirus infection in vivo.

Animals↗
PubMed2001

Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms.

OBJECT: The goal of this study was to investigate the pathological mechanism and precise three-dimensional (3D) structure of cerebral dissecting aneurysms in association with their clinical course. METHODS: Nine aneurysm specimens were excised from eight patients. Of the nine aneurysms, seven arose from the vertebral artery, one from the anterior cerebral artery, and one from the superior cerebellar artery. Eight aneurysms were accompanied with subarachnoid hemorrhage (SAH) and one with infarction. Seven aneurysms were obtained at autopsy and two were obtained during surgery (trapping and bypass). All nine aneurysms were sectioned into serial axial slices measuring 5 to 10 microm in thickness. Taking each slice as an element, we reconstructed the 3D structure of the aneurysm. The true lumen communicated with a pseudolumen through the disrupted portion of the internal elastic lamina (IEL) in all nine aneurysms. The ruptured portion was located just above the disrupted IEL. Two aneurysms had an exit back into the true lumen. but the other seven had no such exit. CONCLUSIONS: The primary mechanism by which a cerebral dissecting aneurysm is created is by the sudden disruption of the IEL. The plane of dissection extends through the media. The majority of aneurysms have one entrance into the pseudolumen (entry-only type). This type is associated with an unstable clinical course. Some cerebral dissecting aneurysms have both an entrance and exit (entry-exit type). This type of aneurysm occasionally contains a constant flow of blood through the pseudolumen and is clinically more stable than entry-only aneurysms.

Adult↗
PubMed2001

Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients.

OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.

Adult↗
PubMed2001

[A point mutation at Arg169 (CGG-->TGG) in hereditary protein C deficiency].

We investigated a 56-year-old Japanese man with protein C deficiency, who was referred to our hospital because of venous sinus thrombosis and pulmonary thromboembolism. Protein C (PC) activity and the corresponding antigen level in plasma were 66% and 106% of the normal values, respectively. Both the activity and antigen levels of protein C were reduced by approximately 50% in plasma from the patient's mother. All exons and their flanking intron regions were amplified by PCR from genomic DNA. Sequencing analysis of the PCR fragments revealed that the patient was heterozygous for a C to T substitution at nucleotide position 6218, resulting in a single amino acid substitution of arginine (CGG) by tryptophan (TGG) at codon 169 of the heavy chain. We analyzed the patient, his mother, and normal controls by a Sac II digestion study of exon 7 and found that the patient and his mother had the same C to T point mutation at base 6218. This mutation could have been responsible for the defective activation of the molecule and the resulting thrombotic disorder. The patient is now being treated with warfarin, and so far no further clinical thrombotic episode has occurred.

DNA Mutational Analysis↗
PubMed2001

[Pulmonary edema in a child following laryngospasm triggered by a laryngeal mask airway during emergence from anesthesia].

A 9-year-old boy underwent biopsy of the tumor at the external auditory meatus under general anesthesia with a laryngeal mask airway(LMA). During emergence from anesthesia, laryngospasm with marked inspiratory effort and cyanosis occurred. The LMA was removed and the patient was orotracheally intubated following vecuronium administration. In spite of controlled ventilation with 100% oxygen, oxygen saturation remained at low 90s and pink frothy sputum appeared in the tracheal tube. We suspected negative pressure pulmonary edema and treated him with mechanical ventilation with positive end-expiratory pressure. Seventeen hours later the pink frothy sputum decreased and he was extubated. Laryngospasm during emergence from anesthesia with an LMA can induce negative pressure pulmonary edema, especially in pediatric patients.

Anesthesia Recovery Period↗
PubMed2001

Epidemiology of tick-borne encephalitis (TBE) and phylogenetic analysis of TBE viruses in Japan and Far Eastern Russia.

In Oshima, the southern part of Hokkaido, a tick-borne encephalitis (TBE) patient was found in 1993; in addition TBE virus was isolated from the blood samples of sentinel dogs, ticks pools, and rodents spleens in 1995 and 1996 by suckling mice. To identify when these TBE viruses emerged in Hokkaido, the times of divergence of TBE virus strains isolated in Oshima and Far Eastern Russia were estimated. TBE virus was isolated in Khabarovsk in 1998, and the nucleotide sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk were compared. Based on the synonymous substitution rates of these virus E-protein genes, the lineage-divergence times of these TBE virus strains were predicted phylogenetically to be approximately 260-430 years ago. Furthermore, the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a mouse model. The results showed that the isolates possessed very similar virulence in mice. European TBE vaccine was found to be effective in TBE virus, Hokkaido strain. This review provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from the Far Eastern Russia a few hundred years ago, which explains why the virulence of these strains is similar to that of TBE viruses isolated in Russia. Practical application of the vaccine should be considered in Japan.

Amino Acid Sequence↗
PubMed2001

[Unilateral pulmonary fibrosis following ipsilateral single-lung ventilation and anesthesia].

We experienced a rare case of unilateral pulmonary fibrosis following ipsilateral single-lung ventilation and anesthesia. A 75-year-old man with a 1-pack a day smoking history for 50 years was scheduled for right upper and middle lobectomy for lung cancer. The trachea and left bronchus were intubated with a 37-Fr double-lumen endobronchial tube, and anesthesia was maintained with oxygen, nitrous oxide, isoflurane, and epidural lidocaine. Left single-lung ventilation was maintained for 3.5 hours with FIO2 at 0.8-1.0, vital capacity at 10 ml.kg-1, and peak inspiratory pressure at 25 cmH2O. On postoperative day 55, reticular nodular density in chest roentogenography appeared only in the left lung while right lung showed pleural fluid and pneumonia. On postoperative day 105, a high-resolution computed tomographic scan revealed honeycomb pattern in the left lung and organized pneumonia in the right lung. The patient died from respiratory failure on postoperative day 155, and autopsy was not performed. Although the causative mechanisms of unilateral pulmonary fibrosis in this case was unclear, the patient had not been exposed to any drugs and inhalation agents known to induce pulmonary fibrosis. We speculate that high oxygen concentration, high peak inspiratory pressure, and overdistension of the left lung during the left single-lung ventilation and anesthesia were likely major initiating and contributing factors.

Aged↗
PubMed2001

[A case of combined operation of aortic valve slicing and root remodeling for ascending aortic aneurysm with aortic regurgitation].

A 56-year-old female admitted with severe back pain, and her chest computed tomography demonstrated non-dissecting sclerotic aneurysm of the ascending aorta. Aortography and echocardiography showed marked dilatation of the ascending aorta and the Valsalva sinuses resulting in disappearance of the sinotubular junction. Aortic regurgitation of grade three was, also, recognized. A combined operation of aortic valve slicing of the right and the left coronary cusps and aortic root remodeling (Yacoub's method) was successfully performed. A woven Dacron double-veloured graft (Hemashield) of 22 mm in diameter was used for reconstruction of the ascending aorta and its root. Postoperative aortography figured the new sinotubular junction and the new Valsalva-like sinus composed by the graft, and aortic regurgitation was controlled to grade one.

Aorta↗
PubMed2001

Epizootiological survey of hantavirus among rodent species in Ningxia Hui Autonomous Province, China.

Hantaviral antibodies were detected in the sera from Apodemus (A.) agrarius and A. peninsulae captured in Ningxia province, China by several different serological diagnostic methods. A total of 409 sera from rodent and insectivore species were collected in 1999 and examined by indirect immunofluorescent antibody assay (IFA). Among them, 19 of 191 (9.9%) sera of A. agrarius and 1 of 13 (7.7%) sera of A. peninsulae were positive for hantaviral antibodies. The other species (Rattus norvegicus, Mus musculus, Cricetulus triton, and Sorex cylindricauda) were negative. The reaction pattern of positive serum was characterized as scattered and granular virus antigens in the cytoplasm of hantavirus infected Vero E6 cells. Some of the A. agrarius sera positive for hantavirus were further examined by Western blotting (WB), enzyme-linked immunosorbent assay (ELISA), and the focus reduction neutralization test (FRNT). By WB, positive sera showed the same specific reaction pattern of baculovirus-expressed recombinant hantaviral nucleocapsid protein, as shown in hantavirus-immune serum. By ELISA, IFA-positive sera showed significantly higher optical densities (around 1.0) than the negative A. agrarius sera. Hantaan type hantavirus was neutralized with the positive sera. These results suggest that A. agrarius have hantavirus infection and may play a role as a reservoir animal for hantavirus in Ningxia Hui Autonomous Province, China.

Animals↗
PubMed2001

[Acute myelogenous leukemia associated with disseminated intravascular coagulation and acute myocardial infarction at relapse].

A 71-year-old man with acute myelogenous leukemia (AML, M2) developed signs of chest oppression, and was diagnosed as having acute myocardial infarction (AMI). At the same time, his leukemia relapsed in association with disseminated intravascular coagulation (DIC). The patient's risk factors for AMI were hyperlipidemia, hyperglycemia, and a history of smoking. Coronary angiography showed occlusion of the circumflex branch. Percutaneous transluminal angioplasty (PTCA) was performed successfully, followed by administration of heparin. After chemotherapy, the patient's DIC improved and a second remission was attained. When elderly patients with AML show evidence of DIC, we should be aware of AMI as a possible complication. PTCA is a safe operation for such patients.

Aged↗
PubMed2001

[A case of Machado-Joseph disease presenting pure cerebellar ataxia].

We report a 61-year-old woman with Machado-Joseph disease (MJD) presenting with pure cerebellar ataxia. The patient exhibited an unsteady gait at the age of 51 years. She was admitted to our hospital at the age of 61 years. Her older brother had been diagnosed as having spinocerebellar degeneration (SCD). Our patient showed gaze-evoked nystagmus, wide-based gait, slight lack of coordination of the four extremities, mildly ataxic speech and slight decrease in the bilateral Achilles tendon reflexes. Babinski's sign was absent. Sensory impairments were not present and muscle tone and muscle strength were normal. There was no autonomic dysfunctions. MRI revealed moderate atrophy of the cerebellum and pons. We performed gene analysis of SCD using white blood cells from the patient, and the analysis showed 70 CAG repeats in the MJD1 gene, which is an abnormally high number of repeats. Compared with three reported cases of MJD presenting pure cerebellar ataxia, only our patient showed a nasal voice. The number of CAG repeats in the MJD1 gene of our patients was the most prolonged of the four cases. MJD should be considered in patients with familial SCD even if their neurological signs and symptoms outside the cerebellum are not obvious.

Ataxin-3↗
PubMed2001

[A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation].

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.

Adult↗
PubMed2001

[Neuro-infections to be borne in mind].

We presented atypical manifestations in tuberculous meningitis (TbM) and herpes simplex encephalitis (HSE), lymphocytic dominant cerebrospinal fluid pleocytosis in bacterial meningitis, and a hitherto easily overlooked critical illness polyneuropathy (CIP) associated with sepsis. 1) We presented 2 TbM patients with atypical manifestations. One patient was a 25-year-old man who exhibited polymorphonuclear (PMN) dominant pleocytosis in CSF throughout his clinical course. He died the next day after a CSF culture yielded the growth of tuberculous bacilli, before receiving appropriate anti-TBM therapy. This was a rare TbM example of persistent PMN dominant CSF pleocytosis. The other patient was a 39-year-old woman whose CSF pleocytosis changed from lymphocytic dominant to PMN dominant about 1 month after the initiation of antituberculous chemotherapy. This CSF change was followed by multiple cerebral infarcts due to vauculitis caused by TbM. Administration of prednisolone caused marked improvement of the patient's symptomatology. Tuberculomas appeared transiently during anti-TbM therapy, consistent with paradoxical progression of tuberculoma. 2) A few patients with HSE may show atypical CSF findings such as PMN dominant pleocytosis, absence of pleocytosis, and low sugar value. Our national survey of HSE patients showed following percentages of these atypical findings: PMN dominant pleocytosis observed in 10% of the patients in the early stage and at the time of exacerbation, no pleocytosis in 0.9% (1 patient), and low sugar value in 4%. 3) Bacterial meningitis typically causes PMN dominant CSF pleocytosis. However, Listeria meningitis (LM) may cause lymphocytic dominant pleocytosis in 30% of the patients, particularly in elderly ones. We showed one such 69-year-old patient with persistent lymphocytic dominant CSF pleocytosis throughout the clinical course. 4) CIP, septic encephalopathy and critical illness myopathy are 3 major complications associated with sepsis. CIP is a frequent cause of neuromuscular weakness due to axonal dysfunction, which occurs to critically ill patients with sepsis, particularly when multiple organ dysfunctions are present. We showed our CIP patient associated with acute bacterial endocarditis and multiple organ failure. We should bear in mind these atypical manifestations, and frequent and important complications associated with sepsis such as CIP, to provide appropriate management to patients with neuro-infection and sepsis.

Adult↗
PubMed2001

Induction of hepatic DT-diaphorase in mice by butylated hydroxyanisole analogs: a structure-activity study.

Butylated hydroxyanisole (BHA) and its analogs were evaluated for their relative activity to induce hepatic DT-diaphorase (EC 1.6.99.2) after dietary administration (at concentrations of 11.1 or 27.7 micromol/g diet for 3 days) to mice. Of the compounds tested, only BHA and 2-tert-amyl-4-methoxyphenol, 4-methoxyphenols with 2-tert-alkyl side chains, were active in inducing DT-diaphorase activity. None of the remaining six compounds showed any significant sign of inducing activity. No simple explanation for these rather strict structural requirements can be offered at the present time.

Administration, Oral↗
PubMed2000

Endogenous AP-1 levels necessary for oncogenic activity are higher than those sufficient to support normal growth.

We investigated the role of endogenous AP-1 in human tumor cell lines by introducing SupJunD-1, a dominant-negative mutant of AP-1, using vesicular stomatitis virus G protein (VSV-G)-pseudotyped retrovirus vectors. Single inoculation of six human tumor cell lines, originating from osteosarcomas, non-small cell lung carcinomas or cervical carcinomas, with recombinant SupJunD-1 virus at a high multiplicity of infection readily inhibited colony formation in soft agar. We detected no significant changes in expression levels of AP-1 components c-Jun or Fra-1, adhesion molecules CD44 or E-cadherin, or cell cycle regulator p53, which are encoded by genes previously reported to be under the control of AP-1 in some mouse or human cell lines. By varying the dosage of VSV-G-pseudotyped retrovirus, we were able to change the proviral copy number of supjunD-1 from 1 to approximately 10 and monitor suppression of endogenous AP-1 function as assessed by growth characteristics of the tumor cell lines, we found a SupJunD-1 dosage which significantly suppressed anchorage-independent growth without affecting the cellular growth in monolayer cultures at all. We conclude that endogenous AP-1 levels necessary for oncogenic activity are much higher than those sufficient to support normal growth.

3T3 Cells↗