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Biomedical subjects

T Ohtsuki

Publications and source records attributed to T Ohtsuki.

At least 55 records · Page 3Linked to original sources

[Evaluation of a combination chemotherapy with nedaplatin and 5-FU for oral cancers].

Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a molecular weight of 303.18 that was recently developed in Japan. There have been reports of the antineoplastic effects of Nedaplatin on cancers in the cranio-cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8 patients with oral cancers, and evaluated the results to elucidate the clinical effect and adverse side effects. The subjects were 8 patients with squamous cell carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day 5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was evaluated as a partial response in all cases, showing a 100% success rate. The histopathological findings of resected tumors were evaluated by Ohboshi and Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and 2 patients Grade III. The adverse side effects were slight myelotoxicity, gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral cancers in this study were extroverted superficial ulcerative cancers, and the number of patients was low at 8, this combined therapy is considered useful and worth evaluating in further accumulated cases.

Adult↗

Regional difference of neuronal vulnerability in the murine hippocampus after transient forebrain ischemia.

We have investigated the regional difference of neuronal vulnerability within the hippocampus in the C57BL/6 strain mice after forebrain ischemia. Both common carotid arteries of fifty mice were occluded for 12 min and the mouse brain was examined with cresyl violet staining. The CA4 sector was found to be the most vulnerable within the hippocampus. The CA2 and the medial CA1 sector was the 2nd and 3rd most vulnerable regions. However, The lateral part of the CA1 sector, CA3 sector and the dentate gyrus were resistant to ischemic insult.

Animals↗

Mutational analysis of the synapsin III gene on chromosome 22q12-q13 in schizophrenia.

Synapsins are a family of neuron-specific, synaptic vesicle-associated phosphoproteins that have been implicated in the modulation of neurotransmitter release. Synapsins are coded by three distinct genes for synapsin I. II, and III. The synapsin III gene is located on human chromosome 22q12-q13, where a possible schizophrenia susceptibility locus is located. Using the single strand conformation polymorphism method, we searched for variants in 13 exons and the 5'-flanking region of the synapsin III gene in schizophrenia. Three polymorphisms, -631C/G, -271T/C, and E525Q, and one rare variant, -669C >A, were identified. Case-control comparisons of these polymorphisms revealed no significant differences in the allelic and genotypic distributions between schizophrenic and control subjects. The present study did not provide evidence for an association between the synapsin III gene and schizophrenia.

Alleles↗

Topology dependent quantities at the anderson transition

The boundary condition dependence of the critical behavior for the three dimensional Anderson transition is investigated. A strong dependence of the scaling function and the critical conductance distribution on the boundary conditions is found, while the critical disorder and critical exponent are found to be independent of the boundary conditions.

Journal Article↗

Ultrastructural study on calcification of cartilage: comparing ICR and twy mice.

Twy mice are autosomal recessive mutant mice that develop multiple progressive abnormal calcification, mainly of the cartilage or tendons of the spine and limbs. They finally succumb to severe deformation and ankylosis. We carried out an ultrastructural study on the growth plate as well as the articular and spinal disc cartilage of twy mice and control ICR mice. Knee and spinal specimens were obtained from the animals, then prepared using standard procedures. Ultrastructural observations were made on uranyl lead-stained sections and elemental analysis was carried out on unstained sections. In both twy and ICR mice, linked granules (chain granules) were observed at the pericellular matrix, but there was no remarkable difference between their presence in the growth cartilage. In the twy mice, however, chain granules were observed in the pericellular matrix, cytoplasm, and nucleus of the articular and spinal disc cartilage. These chain granules disappeared after decalcification. Elemental analyses revealed significant amounts of calcium and phosphorus in these granules. It may be significant for abnormal calcification that such chain granules were observed in the articular and spinal disc cartilage of twy mice.

Animals↗

WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder.

BACKGROUND: Wolfram syndrome (WFS) is an autosomal recessive neurodegenerative disorder. Recently, the WFS1 gene was isolated, and approximately 80% of the mutations responsible for WFS were found in exon 8 of WFS1. It has been noted that heterozygous carriers of the WFS gene are 26-fold more likely to be hospitalized for depression, and it has been estimated that approximately 25% of all people hospitalized for depression may carry the WFS gene(s). METHODS: We searched for mutations in exon 8 of WFS1 in 30 depressive patients with a history of hospitalization and whose age at onset was under 40 years. We also examined 47 bipolar affective patients and 62 control subjects for an association. RESULTS: A were detected. Four of the six were novel. No nonsense or frameshift mutation was detected. Genotypic and allelic distributions were similar between the depressive patients and the controls. No association with bipolar affective disorder was suggested. LIMITATIONS: Because of the small sample size, the probability of finding at least one patient with WFS-responsible mutation(s) was 70% if depression is associated with WFS1 mutation(s) in 5% of patients. CONCLUSION: It is not likely that WFS1 mutations are responsible for as much as 25% of depressive illness.

Adult↗

Unique N-linked glycosylation of murine coronavirus MHV-2 membrane protein at the conserved O-linked glycosylation site.

The membrane (M) proteins of murine coronavirus (MHV) strains have been reported to contain only O-linked oligosaccharides. The predicted O-glycosylation site consisting of four amino acid residues of Ser-Ser-Thr-Thr is located immediately adjacent to the initiator Met and is well conserved among MHV strains investigated so far. We analyzed the nucleotide sequence of a highly virulent strain MHV-2 M-coding region and demonstrated that MHV-2 had a unique amino acid, Asn, at position 2 at the conserved O-glycosylation site. We also demonstrated that this substitution added N-linked glycans to MHV-2 M protein resulting in increment of molecular mass of MHV-2 M protein compared with JHM strain having only O-linked glycans.

Amino Acid Sequence↗

Extended neuronal protection induced after sublethal ischemia adjacent to the area with delayed neuronal death.

In the present study, we investigated whether neurons adjacent to an ischemic lesion acquire tolerance against subsequent ischemia or not. We initially used unilateral hemispheric ischemia for 3 min in gerbils to produce an ischemic lesion confined to the unilateral CA1 sector, and the presence of tolerance was examined in the adjacent CA3 sector through transient global ischemia by occlusion of both common carotid arteries. Attenuation of neuronal damage was clearly observed in neurons in the CA3 sector adjacent to the ischemic lesion in the CA1 sector. The phenomenon lasted for up to two weeks after the initial hemispheric ischemia, but was no longer present two months later. Reactive astrocytes as identified by the presence of glial fibrillary acidic protein were visible in the CA3 hippocampus four days and two weeks after hemispheric ischemia, but they were scarce two months later. Expression of heat shock protein 72 in the CA3 neurons was observed four days after hemispheric ischemia, but the reaction returned to the control level two weeks later. In conclusion, the present study showed that tolerance in the neurons adjacent to an ischemic lesion could be sustained at least for two weeks, and raised the possibility that reactive astrocytes might contribute to the extended tolerance in neurons.

Animals↗

Good or evil: CD26 and HIV infection.

Acquired immune deficiency syndrome (AIDS) is an incurable disease at present and so many efforts to conquer this disease are being made around the world. In studies of human immunodeficiency virus (HIV) infection and the disease progression, it has been reported that T cells expressing CD26 are preferentially infected and depleted in HIV-infected individuals. CD26 is a widely distributed 110 kDa cell-surface glycoprotein with known dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. This ectoenzyme is capable of cleaving N-terminal dipeptides from polypeptides with either proline or alanine residues in the penultimate position. On human T cells, CD26 exhibits the co-stimulatory function and plays an important role in immune response via its ability to bind adenosine deaminase (ADA) and association with CD45. Recent studies have been stripping the veil from over the relationship between CD26 and HIV infection. Susceptibility of cells to HIV infection is correlated with CD26 expression, and HIV transactivator Tat and envelope protein gp120 are reported to interact with CD26. These observations indicate that CD26 is closely involved in HIV cell entry and that CD26-mediated T cell immune response is suppressed. In addition, it has been demonstrated that the anti-HIV and chemotactic activities of RANTES (regulated on activation, normal T cell expressed and secreted) and stromal cell-derived factor-1 (SDF-1) are controlled with the DPPIV activity of CD26. Thus, the regulation of the function of chemokines by CD26/DPPIV appears to be essential for lymphocyte trafficking and infectivity of HIV strains.

Amino Acid Sequence↗

EMG analysis of lower limb muscles in humans during quick change in running directions.

Open and cross maneuvers for changing running direction were studied to characterize selective EMG activity between the maneuvers. Eleven subjects turned towards the right or the left during running. The gluteus medius modified foot trajectory of the leading leg during the open maneuver, whereas the sartorius worked modestly during the cross maneuver. Compared with the cross maneuver the open maneuver exhibited greater vastus medialis and gastrocnemius activity during the ground support phase, faster running speed and wider turning angle. These results suggest that the open maneuver is more effective than the cross maneuver for quickly changing running direction.

Adult↗

Differential angle-dependent modulation of the long-latency stretch reflex responses in elbow flexion synergists.

We determined the effect of elbow joint angle on the short-(M1) and long-latency stretch reflex (M2 and M3) responses of the elbow flexion synergists, the brachioradialis (BR), and the biceps brachii (BB), during weak isometric elbow flexion tasks. The elbow joint angle was 35,75 and 115 degrees (full-extension angle was 0 degrees ), and the muscle contraction level was 0,3 and 6% of maximum voluntary contraction (MVC) of the BR. In BR, the M1, M2 and M3 responses were significantly greater at 75 and 115 degrees than at 35 degrees. On the other hand, in BB, the M2 response was significantly greater at 35 degrees than at 75 and 115 degrees, while the M1 and M3 responses were not significantly different among the elbow joint angles. These results indicated that the stretch reflex responses of BR might be dependent on the changes of muscle length in stretch stimulus, while the M2 response of BB might not be dependent on the actual stimulus intensity. Therefore, we concluded that the M2 of BB might be modulated selectively by a higher reflex center in accordance with relationships of the mechanical advantages between synergistic muscles.

Adult↗

Muscle activity and accuracy of performance of the smash stroke in badminton with reference to skill and practice.

The aims of this study were to establish the temporal-spatial relationship between muscle activity and the smash stroke of skilled badminton players and to assess performance accuracy using the ellipse of constant distance. We recorded the surface electromyographic (EMG) activity of selected superficial muscles of the stroking arm and shoulder--flexor carpi ulnalis, extensor carpi radialis, triceps brachii (lateral head), biceps brachii and trapezius (upper)--during the badminton smash. In the first part of the study, we examined the characteristics of muscle function and performance accuracy of skilled and unskilled individuals during the badminton smash. Five well-trained badminton players and five students with no experience of badminton were asked to smash a shuttle as hard as they could towards a vertical square target 4 m away, repeating the stroke 30 times. In general, the skilled players showed a more constant time from peak electromyographic amplitude to impact. Immediately after impact, the electromyographic activity of the triceps brachii and flexor carpi radialis of the skilled players decreased; in the unskilled participants, however, it continued until well after impact. The area of the ellipse of constant distance and the off-target distance, which were used as indices of performance accuracy, were smaller for the skilled than for the unskilled participants. In the second part of the study, one skilled and one unskilled participant performed 100 trials a day for 6 days. The time from peak electromyographic amplitude to impact in the extensor carpi radialis and flexor carpi ulnalis was more variable in the unskilled than in the skilled participant even after 6 days of practice, but the proximal muscles of the unskilled participant had a similar pattern of activity to that of the skilled player. Thus, controlling the distal muscles appears to be important for achieving accurate performance of the smash in badminton.

Adolescent↗

Unnatural base pairs between 2-amino-6-(2-thienyl)purine and the complementary bases.

The unnatural base, 2-amino-6-(2-thienyl)purine (designated as s), instead of 2-amino-6-(N,N-dimethylamino)purine (designated as x), was designed in order to improve the specificity and efficiency of the base pairing with pyridin-2-one (designated as y). DNA fragments containing s were chemically synthesized, and the thermal stability and the enzymatic reactions involving the s-y pairing were examined. Thermal denaturation experiments showed that the DNA duplex (12-mer) containing the s-y pair was more stable than that containing the x-y pair. The incorporation of dyTP was also more advantageous to the s-y pairing than the x-y pairing in single-nucleotide insertion experiments using the Klenow fragment of Escherichia coli DNA polymerase I.

Base Pairing↗

Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The purpose of this study was (1) to examine the contribution of microglia and macrophages with their interleukin-1beta production and (2) to assess the vulnerability and response of oligodendrocytes in cerebral infarction. METHODS: Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of oligodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1beta, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the expression of proapoptotic Bax protein. RESULTS: During expansion of infarction, amoeboid microglia and extravasation of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the boundary and granulocytes migrated into the center of the infarction. Both amoeboid microglia and macrophages produced interleukin-1beta, an inflammatory cytokine, during an early ischemic period. Furthermore, macrophages within the infarcted tissue expressed Bax protein and subsequently showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subsequently developed fragmented DNA. A week after onset of ischemia, oligodendrocytes were found to be accumulated in the intact area bordered with the infarct together with reactive astrocytes. CONCLUSIONS: Our results suggest the importance of amoeboid microglia, macrophages, and their interleukin-1beta production in gradual expansion of cerebral infarction. Resident oligodendrocytes may be resistant to ischemic insults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.

Animals↗

Drug targeting efficacy to underlying muscle following topical application. I. Evaluation based on a physiological pharmacokinetic model.

A physiological pharmacokinetic model describing the absorption and disposition of topically applied drugs was proposed, and the effect of various pharmacokinetic and physiological parameters on the drug delivery into the targeted muscle was simulated. The proposed model consists of vehicle, and stratum corneum, viable epidermis and muscle below the application and reference sites, and plasma, each joined with transfer clearance and plasma flow. Indomethacin concentrations in tissues and plasma after topical application to rats could be explained by the model. Most indomethacin delivered into the underlying muscle was via direct penetration. The model simulation showed that the increase in plasma clearance and clearance between viable skin and muscle, and the decrease in application area and plasma flow rate into viable skin and muscle would promote the targeting efficacy of topically applied drugs to the underlying muscle.

Administration, Topical↗

Deficiency of intercellular adhesion molecule 1 fails to mitigate selective neuronal death after transient global ischemia.

Recent studies have shown a crucial role of intercellular adhesion molecule 1 (ICAM-1) in expansion of infarction after focal cerebral ischemia. The purpose of the present study was to assess whether ICAM-1 is involved in selective neuronal vulnerability and reactive gliosis after transient forebrain ischemia. ICAM-1 knockout mice and wild-type mice were subjected to transient forebrain ischemia for 5, 10 or 15 min, and the hippocampus and caudoputamen were examined 7 days later with conventional histological and immunohistochemical methods. Bilateral common carotid artery occlusion with less than 10% of baseline cortical microperfusion for 10 or 15 min resulted in ischemic neuronal damage in the hippocampus and caudoputamen. The frequency and the severity of neuronal damage were similar in wild-type and knockout mice. Proliferation of reactive astrocytes in the hippocampus was also similar in both types of mice. Therefore, it is highly unlikely that ICAM-1 plays a key role in delayed neuronal death after transient global ischemia or in astroglial responses after ischemic neuronal injury.

Animals↗

Abnormal blinking of newscasters.

When compared with a control group, blink rates of Japanese TV newscasters were increased, suggesting a possible reaction to reading the news under stressful studio conditions. Frequent blinking may be distractive to the viewing audience.

Adult↗