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Biomedical subjects

K Tohyama

Publications and source records attributed to K Tohyama.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dynamic 99Tcm-ECD SPET correlates well with 201Tl indices in brain tumours.

The dynamic 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) single photon emission tomographic (SPET) characteristics of brain tumours were investigated and compared with 201Tl-chloride SPET indices. Thirty-five patients with histologically confirmed benign and malignant tumours were evaluated using dynamic and standard 99Tcm-ECD. Twenty-eight patients were also examined using standard 201Tl SPET. The following 201Tl indices were calculated: early uptake ratio, delayed uptake ratio, washout rate and retention index. The relationship between uptake of 99Tcm-ECD on dynamic SPET and 201Tl indices was analysed. Nine patients showed positive uptake on dynamic 99Tcm-ECD SPET, all of whom had benign tumours, including five meningothelial meningiomas, three pituitary adenomas of the chromophobe type and one chemodectoma without malignancy. The mean early uptake ratio of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (17.1 +/- 5.5 vs 9.0 +/- 5.7, P = 0.004). The mean washout rate of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (61.0 +/- 27.7 vs 0.35 +/- 30.9, P = 0.0004). The mean retention index of the tumours with positive uptake was significantly lower than that of the tumours with negative uptake (0.27 +/- 0.12 vs 0.88 +/- 0.48, P = 0.000006). Only benign tumours showed positive uptake on dynamic 99Tcm-ECD SPET. The 201Tl indices correlated well with the uptake of 99Tcm-ECD on dynamic SPET. The results suggest that dynamic 99Tcm-ECD SPET can identify the benign character of tumours of the brain.

Adult↗
PubMed1999

Isolation and molecular characterization of a poliovirus type 1 mutant that replicates in the spinal cords of mice.

The Mahoney strain of poliovirus type 1 (OM) is generally unable to cause paralysis in mice. We isolated a mouse-adapted mutant, PV1/OM-SA (SA), from the spinal cord of a mouse that had been intracerebrally inoculated with OM. SA showed mouse neurovirulence only with intraspinal inoculation, and the infected mice developed a flaccid paralysis, which was indistinguishable from that observed in poliovirus-sensitive transgenic mice inoculated with OM. SA antigens were detected in neurons of the spinal cords of the infected mice. Nucleotide (nt) sequence analysis revealed 9 nt changes on the SA genome, resulting in three amino acid (a.a.) substitutions, i.e., one each in the capsid proteins VP4 and VP1 and in the noncapsid protein 2C. To identify the key mutation site(s) for the mouse neurovirulence, virus recombinants between OM and SA were constructed by using infectious cDNA clones of these two viruses and tested for their mouse neurovirulence after inoculation via an intraspinal route. The results indicated that a mutation at nt 928 (replacement of A with G), resulting in a substitution of Met for Ile at a.a. 62 within VP4, was responsible for conferring the mouse neurovirulence phenotype of the mutant SA. The mutation in VP4 may render the virus accessible to a molecule that acts as a virus receptor and is located on the surfaces of neurons of the mouse spinal cord. This molecule appears not to be expressed in the mouse brain.

Adaptation, Physiological↗
PubMed1999

[Prototype of a new pediatric emergency scale tape: PES tape].

Drug dosage and appropriate size of medical equipment for emergency pediatric patients are determined by age, body weight and/or height. In an emergency situation, however, such information about the patients is not always clear. Body height is easily measured when the patient lies down supine. Furthermore, child's height could be a better parameter than age to predict appropriate endotracheal tube (ETT) size and body weight. We propose a new pediatric emergency scale tape (PES Tape). PES Tape is graduated in centimeters to measure body height in supine position. Height-based body weight, drug dosage, energy dosage for defibrillation, appropriate size of ETT and lip-tip distance (LTD) are printed on the tape. We studied the reliability of this tape in pediatric anesthesia. Body weight estimated from the tape was accurate, and predicted size of ETT and LTD was appropriate. PES Tape is a reliable tool in pediatric emergency.

Body Weights and Measures↗
PubMed1998

Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK.

The function and the outside-in signaling pathways of alphaIIbbeta3 were examined in relation to cell adhesion using a megakaryoblastic leukemia cell line, CMK. After 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, the cells adhered to the culture plate and underwent megakaryocytic differentiation with expression of alphaIIbbeta3. Binding of soluble fibrinogen to the cells via alphaIIbbeta3 was dependent on cell adhesion. Cell detaching reduced the affinity of this integrin for soluble fibrinogen, although its surface expression was almost unchanged. In contrast, detached cells became tightly adherent to the fibrinogen-coated plate (solid-phase fibrinogen). The same ligand, fibrinogen, present either in soluble or solid-phase form, triggered differential signaling pathways mediated by alphaIIbbeta3. By the stimulation with soluble fibrinogen, Syk was tyrosine-phosphorylated but FAK was dephosphorylated, whereas solid-phase fibrinogen promptly caused tyrosine phosphorylation of FAK followed by delayed phosphorylation of Syk. In addition, the binding of soluble fibrinogen to the cells adherent to fibrinogen-coated plate resulted in tyrosine phosphorylation of integrin beta3 and a complex formation of integrin beta3 with Syk. This implies the cooperation of both soluble and solid-phase fibrinogen-mediated signaling pathways.

Cell Adhesion↗
PubMed1998

Long acellular nerve transplants for allogeneic grafting and the effects of basic fibroblast growth factor on the growth of regenerating axons in dogs: a preliminary report.

Sciatic nerves were excised from 3 beagle dogs about 5 h after their sacrifice, treated three times by freezing and thawing, and stored in physiological saline for 3 months at -20 degrees C until used. Nerve segments 5 cm in length prepared from these stored nerves were transplanted to the common peroneal nerve in the right hindlimb of beagle dogs. Sixteen beagle dogs in total were used, in four treatment groups of two pairs each studied at 1 and 3 months. Five-hundred microliters basic fibroblast growth factor (bFGF) of two different concentrations (10 micrograms/300 microliters and 100 micrograms/300 microliters) which were impregnated in 0.5 ml gelatin hydrogels was applied around the sutured allografts. Autografting was also done in 4 beagle dogs, with no bFGF application. One month after the grafting, no regenerating nerves extended beyond the middle of the transplant in any of the allografts, except in the autografts in which a number of regenerated (myelinated) axons were present. Three months after the grafting, an abundance of myelinated axons was found at the middle of the graft: the numbers of axons per 10(4) micron 2 were 22.6 in the autografts and 10.6, 10.4 and 19.2 in the allografts treated with no bFGF, low-dose bFGF, and high-dose bFGF, respectively. Regenerating axons extended into the host nerve: the numbers of myelinated axons at the level 1.5 cm distal to the distal suture were 35.7, 0.9, 3.8, and 12.1 per 10(4) micron 2 in the above respective order. Although it was inferior in quality to the autograft, peripheral nerve regeneration was extensive in the distal nerve using freeze-thawed and bFGF-treated allografts at 3 months. Electromyography showed that the peroneus longus muscle responded to the electrical stimuli given at the site proximal to the transplant in all four groups. These data indicate that a 5-cm acellular nerve segment containing Schwann cell basal laminae can be used successfully as an allograft without any immunosuppressants and that exogenously applied bFGF can improve nerve regeneration by enhancing the growth of regenerating axons.

Animals↗
PubMed1998

Spread of swine hemagglutinating encephalomyelitis virus from peripheral nerves to the CNS.

Swine hemagglutinating encephalomyelitis virus (HEV) strain 67N was inoculated into the sciatic nerve or the right leg crural muscle of rats. In both cases, the virus was isolated first from the caudal half of the spinal cord on day 2 after inoculation, and from the rostral half of the spinal cord and the brain on day 3. The virus titers in the brain reached a maximum when the infected rats developed CNS symptoms on day 5. Using confocal laser scanning microscope, fluorescent positive cells were first found in the lumbar dorsal root ganglion (DRG) and spinal cord ipsilateral of the inoculated leg on day 3. Antigen positive neurons were found bilaterally in the lumbar DRG and spinal cord on day 4. On day 5 specific fluorescence was observed in the neurons of the cerebral cortex, hippocampus, brainstem and Purkinje cells in the cerebellum.

Animals↗
PubMed1998

Diagnostic and biological significance of sideroblastic erythropoiesis in the myelodysplastic syndromes.

We retrospectively reviewed clinical and hematologic features of nine patients with acquired idiopathic sideroblastic anemia (AISA). Seven of them had ringed sideroblasts (RS) more than 15% of marrow nucleated cells. RS persisted in the marrow even in the remaining two patients who had a relatively low marrow erythroblasts despite RS ranging from 1/4 to half of the marrow erythroid series. However, RS declined in proportion in another two patients of the nine whose disease progressed to refractory anemia with excess of blasts (RAEB), although a high proportion of RS reappeared in one patient at the time of relapse following allogeneic marrow transplantation. A similar decline of RS concomitant with disease progression was also seen in seven additional patients with RAEB or RAEB in transformation (RAEB-t) with sideroblastic erythropoiesis. Cytogenetic abnormalities, although rare initially, became detectable either at the time of disease progression or at the worsening of anemia in AISA. These observations suggest that the majority of AISA fall in the category of myelodysplasia, and that a progressive decline in RS is part of the natural history of myelodysplasia. Closer follow-up of the proportion of RS in patients with AISA is warranted to better understand its biologic significance.

Adolescent↗
PubMed1998

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes.

Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB-t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.

Blood Platelets↗
PubMed1997

Interleukin-3 activates Syk in a human myeloblastic leukemia cell line, AML193.

Protein-tyrosine kinases and phosphatases play an important role in cytokine-mediated cell growth. The proliferation of a human myeloid leukemia cell line, AML193, is dependent on interleukin-3 (IL-3) or granulocyte colony-stimulating factor. In the current study, we demonstrated that a non-receptor-type protein-tyrosine kinase, Syk, was immediately activated by the stimulation with IL-3 or granulocyte colony-stimulating factor in AML193 cells. We further investigated the relation of Syk with IL-3-mediated signaling and found that the IL-3 receptor beta subunit was immunoprecipitated with Syk. Since the IL-3 receptor beta subunit is known to mediate growth signaling, our results indicate that Syk may be involved in the proliferation of myeloid cells.

Blotting, Western↗
PubMed1997

Remyelination in the rat dorsal funiculus following demyelination by laser irradiation.

Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular components in the dorsal funiculus at the lumbar level (L2) of the rat spinal cord. An open lesion was not found at the irradiation site on the spinal cord. However, the cytological examination revealed that cellular components were damaged to the depth of 200-500 microm from the pial surface. The characteristic feature was that at the border of the lesion, many axons remained naked but intact after their myelin sheaths had been completely disintegrated. Such naked axons were subsequently remyelinated by mature or immature glial cells. Mature oligodendrocytes, while retaining their cytoplasmic processes connected with the myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby naked axons and made new myelin sheaths around them. In contrast, 7 days after the irradiation, numerous immature glial cells appeared in association with naked axons, and some of them were differentiated into oligodendrocytes forming thin myelin sheaths on naked axons. These findings suggest that demyelinated axons can cause the proliferation and probably dedifferentiation of the oligodendrocyte lineage. The use of lasers provides a unique experimental model of demyelination and remyelination in the central nervous system of adult mammals.

Animals↗
PubMed1997

Human factor-dependent leukemia cell lines.

To date several factor-dependent leukemia cell lines have been established. These cell lines have greatly contributed to the analyses of cytokine-mediated cellular signaling mechanisms involved in cell proliferation, differentiation and survival. In addition, they are ideal and practical models for testing the hypothesis regarding leukemogenesis. Taken together, factor-dependent leukemia cell lines are expected to be useful for studies on cell biology and development of new cancer therapeutics.

Cytokines↗
PubMed1997

Vitamin K2 and its derivatives induce apoptosis in leukemia cells and enhance the effect of all-trans retinoic acid.

Geranylgeraniol, a polyprenylalcohol composing the side chain of vitamin K2 (VK2), was previously reported to be a potent inducer of apoptosis in tumor cell lines (Ohzumi H et al, J Biochem 1995; 117: 11-13). We examined the apoptosis-inducing ability of VK2 (menaquinone 3 (MK3), MK4 and MK5) and its derivatives such as phytonadione (VK1), as well as polyprenylalcohols with side chains of various lengths including farnesol (C15-OH; FO), geranylgeraniol (C20-OH; GGO), and geranylfarnesol (C25-OH; GFO) toward leukemia cells in vitro. MK3, MK4, MK5 and GFO (at 10 microM) showed a potent apoptosis-inducing activity for all freshly isolated leukemia cells tested and for leukemia cell lines such as NB4, an acute promyelocytic leukemia (APL)-derived cell line and MDS92, a cell line derived from a patient with myelodysplastic syndrome, although there were some differences depending on the cells tested. In contrast, VK1 showed no effect on any of the leukemia cells. The combination of MK5 plus all-trans retinoic acid (ATRA) resulted in enhanced induction of apoptosis in both freshly isolated APL cells and NB4 cells as compared to each reagent alone. These data suggest the possibility of using VK2 and its derivatives for the treatment of myelogenous leukemias, including APL.

Apoptosis↗
PubMed1997

Relationship between the nature of mucus and crypt multiplicity in aberrant crypt foci in the rat colon.

Aberrant crypt foci (ACF) induced in the distal colon of F344 male rats, 4, 8, 12 and 35 weeks after the first administration of 1, 2-dimethylhydrazine-2HCl (DMH) were examined to determine whether a correlation exists between the nature of goblet cell mucin and the number of crypts (crypt multiplicity) comprising the ACF. According to the ACF score calculated from the results of the qualitative observation of sulfomucins (SuMs) and sialomucins (SiMs), the ACF in the 4th week showed a weak correlation between the nature of the mucus and crypt multiplicity, and the ACF of each class showed similar mucous profiles. From the 8th week, a significant difference (P < 0.01) was recognized between the ACF consisting of 3 crypts or less and those consisting of 4 crypts or more. The proportion of crypts with SiM predominance showed a decrease in the 8th week in the ACF consisting of 1 crypt and in the 12th week in the ACF consisting of 2 or 3 crypts, implying a recovery tendency. The ACF consisting of more than 4 crypts showed little change over time, retaining the tendency of SiM predominance. Ulex europaeus agglutinin-I (UEA-I) lectin-positive crypts appeared in the ACF. This finding was significantly more prominent (P < 0.001) in the ACF with SiM predominance than in the ACF with SuM predominance at each experimental period, and in the 12th week after the first administration of DMH, the incidence of ACF with UEA-I-reactive mucin was decreased in the ACF groups consisting of 3 crypts or less, compared with the ACF groups consisting of 4 or more crypts. These results suggest that the biological quality of mucus in ACF consisting of 4 or more crypts is different from that in ACF consisting of 3 crypts or less. This difference should be considered when ACF are used as an intermediate biomarker of colon cancer.

1,2-Dimethylhydrazine↗