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Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 19 recordsLinked to original sources
PubMed2006

Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment.

A recent study disclosed that breast cancer cases with low 'tau' expression can predict susceptibility to Paclitaxel administration. In the current study, the clinical significance of tau expression in gastric cancer cases was established by identifying candidates with Paclitaxel administration. Tissue specimens from 20 cases of in-operable or noncuratively resected gastric cancer were examined. Subsequent to the administration of 80 mg m(-2) of Paclitaxel in six 3-h intravenous infusions, the clinical effectiveness of Paclitaxel was evaluated by the size of metastatic lesions with computed tomography. The status of the tau expression was determined by immunohistochemistry. Based on a previously reported classification scheme, six were classified as tau-negative expression (0, 1+) cases and 14 were classified as tau-positive expression (2+, 3+) cases. All six (100%) cases of tau-negative expression showed a favourable response (partial response or minor response) to Paclitaxel administration. However, 12 (86%) of the 14 cases of tau-positive expression showed progressive disease (n = 11) or no change (n = 1) after Paclitaxel administration. The serum carcinoembryonic antigen values of the six cases of tau-negative expression were markedly decreased in comparison to the 14 tau-positive cases. These data indicate that tau-negative expression can be used to select gastric cancer patients, which will favourably respond to Paclitaxel treatment.

Adenocarcinoma↗
PubMed2006

Identification and analysis of MHC class II DRB1 (Patr-DRB1) alleles in chimpanzees.

The MHC-DRB1 gene is known to display the most extensive allelic polymorphisms among MHC class II genes. We attempted the selective identification of chimpanzee (Pan troglodytes) DRB1 (Patr-DRB1) alleles using the polymerase chain reaction (PCR) technique in three steps: first, we performed Patr-DRB1*02 lineage-specific 8-kb PCR for *02 lineage detection in each chimpanzee; second, we performed 620-bp PCR for amplification of full-length exon 2; and finally, we carried out an insert check using the pattern of microsatellite repeat length variability. In the genomic DNA of 23 chimpanzees, nine Patr-DRB1 alleles containing two new alleles were detected. Our approach provides a relatively effective method of identifying Patr-DRB1 alleles in individual chimpanzees and should also contribute to our understanding of the features of MHC molecules in non-human primates.

Alleles↗
PubMed2005

Morphological variation in a toroid generated from a single polymer chain.

A single semiflexible polymer chain folds into a toroidal object under poor solvent conditions. In this study, we examined the morphological change in such a toroidal state as a function of the cross-sectional area and stiffness of the chain together with the surface energy, which characterizes the segmental interaction parameter. Changes in the thickness and outer/inner radius on a toroid are interpreted in terms of these parameters. Our theoretical expectation corresponds to the actual morphological changes in a single giant DNA molecule as observed by electron microscopy.

Journal Article↗
PubMed2005

Localization of ubiquitin carboxyl-terminal hydrolase-L1 in cynomolgus monkey placentas.

Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) is a restrictedly expressed enzyme in neural and reproductive tissues, and it is considered to have a significant role in reproduction. In the present study, we investigated the localization of UCH-L1 in placenta of cynomolgus monkeys (Macaca fascicularis). UCH-L1 protein was detected in cytotrophoblasts of chorionic plate and villi, and decidual cells of decidua basalis in cynomolgus monkey placenta, and the amount of UCH-L1 protein in whole placenta increased as pregnancy progressed. These results supported that UCH-L1 is necessary for placental and fetal development in primate placenta. This is the first report to demonstrate the presence of UCH-L1 in primate placenta, and the cynomolgus monkey may be a useful model for the study of the functions of the ubiquitin-proteasome system in human pregnancy.

Animals↗
PubMed2005

A rare case of the cutaneous form of adult T-cell leukaemia/lymphoma: assessment of remission by PCR for clonal T-cell receptor gamma gene rearrangements in an electron beam-irradiated cutaneous lesion.

Adult T-cell leukaemia/lymphoma is a lymphoproliferative disorder aetiologically associated with human T-cell lymphotropic virus type I infection. A cutaneous lesion often develops in the disease, and in rare cases, is even the only manifestation. Here we report a rare case of 'cutaneous' adult T-cell leukaemia/lymphoma with neither atypical cells in the peripheral blood nor lymph node involvement. All nodular lesions were completely eliminated after local electron beam irradiation (20 Gy/nodule in total). To evaluate whether or not there were residual lymphoma cells in the skin, we performed PCR to detect clonal T cell receptor gamma gene rearrangements. The sample from the nodule before irradiation showed evidence of a rearranged band, which was not detected at the same site after treatment nor in any peripheral blood. The findings suggest that this procedure is useful for the evaluation of therapeutic effects and the early detection of lymphoma recurrence.

Female↗
PubMed2005

Age-related changes of intracellular Abeta in cynomolgus monkey brains.

To confirm the intracellular accumulation of amyloid beta-protein (Abeta), we carefully performed immunohistochemistry using brains of cynomolgus monkeys of various ages. Cortical neurones and their large neurites were immunostained with antibodies against Abeta in young monkey brains. In aged monkey brains, intracellular Abeta localized within cortical neurones; no clear association was found between the presence of intracellular Abeta and senile plaques (SPs). Interestingly, we did not observe Abeta-immunoreactive cortical neurones in brains fixed with neutral buffered formalin. Western blot analyses of microsomal and nerve ending fractions derived from the brains of young to aged monkeys revealed that intracellular Abeta generation changed with age. In the microsomal fraction, the amount of Abeta42 significantly increased in brains from older monkeys (>30 years of age), and the amount of Abeta43 significantly decreased with age in the microsomal fraction. The amount of Abeta40 remained the same regardless of age. Biochemical analyses also showed that intracellular levels of each of these Abeta molecules significantly increased with age in nerve ending fractions. As we previously observed that a similar accumulation of presenilin1, beta-amyloid precursor protein (APP) and APP C-terminal fragment cleaved by beta-secretase in the nerve ending fractions obtained from brains with SPs, the accumulation of intracellular Abeta in this fraction may be closely related to formation of spontaneous SPs with age. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending will contribute to a better understanding of the pathogenesis of age-related neurodegenerative disorders such as sporadic Alzheimer's disease.

Aging↗
PubMed2005

Sequence analysis of the MHC class II DPB1 gene in chimpanzees (Pan troglodytes).

The diversity of the MHC class II region in non-human primates is a focus of biomedical research because this region plays a crucial role in the recognition of antigens in the immune system. In particular, the chimpanzee [Pan troglodytes (Patr)], which belongs to the superfamily Hominoidea, has been used as a human model for the study of diseases such as human hepatitis C virus (HCV), human hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, to which only humans and chimpanzees are susceptible. In the present study, polymorphisms of the MHC-DPB1 gene (Patr-DPB1) in a chimpanzee colony in Japan were examined using a stepwise polymerase chain reaction (PCR) technique. In order to design a suitable primer pair which would amplify exon 2 of the Patr-DPB1 gene, a fragment of approximately 8 kb from exon 1 to exon 3 was amplified from chimpanzee genomic DNA. After designing a 500-bp primer pair at the 3' region of intron 1 and the 5' region of intron 2, analysis of DPB1 exon 2 alleles of each chimpanzee was carried out. Twenty-two chimpanzees were used in our study, and we identified seven alleles by sequence analysis on the Patr-DPB1 gene, including one new allele. The obtained nucleotide sequence patterns suggest that Patr-DPB1 alleles emerge by genetic variations such as the exchange of sequence motifs and the accumulation of point mutations.

Alleles↗
PubMed2004

Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils.

Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed neuronal death induced by transient global ischemia in gerbils, even when the vector was administered several hours after ischemia. Intraventricular administration of SeV vector directed high-level expression of the vector-encoded neurotrophic factor genes, which are potent candidates for the treatment of neurodegenerative diseases. After occlusion of the bilateral carotid arteries of gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or vascular endothelial growth factor (SeV/VEGF) was injected into the lateral ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the ischemic insult effectively prevented the delayed neuronal death of the hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of these neurons. These results indicate that SeV vector-mediated gene transfer of neurotrophic factors has high therapeutic potency for preventing the delayed neuronal death induced by transient global ischemia, and provides an approach for gene therapy of stroke.

Animals↗
PubMed2004

[On-pump beating aortic valve replacement for severe aortic regurgitation due to infective endocarditis].

A 37-year-old man was suffering from pneumonia and severe aortic regurgitation due to acute aortic valve endocarditis with the annular abscess with Staphylococcus aureus. Preoperative serum brain natriuretic peptide was over 2,000 pg/ml. Preoperative arterial oxygen saturation was 82% on mechanical ventilation (Fio2: 1.0) with nitric oxide inhalation. Under a full median sternotomy, total normothermic cardiopulmonary bypass was established. Using the normothermic retrograde continuous coronary sinus perfusion of oxygenated blood, on-pump beating aortic valve replacement (AVR) was performed. Veno arterial bypass was required for 72 hours postoperatively. Postoperative course was otherwise uneventful. On-pump beating AVR seemed to be one of the useful procedures for a high-risk patient.

Adult↗
PubMed2004

[Schizophrenia and ocular misalignment: phenotypic and genetic association analysis].

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that constant exotropia displays marked association with schizophrenia. To assess the genetic mechanisms, we examined the transcription factor genes ARIX and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia. The polymorphisms were also associated with overall schizophrenia and more specifically with schizophrenia manifesting strabismus. These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B.

Exotropia↗
PubMed2003

Gallium-67 scintigraphy in the diagnosis and management of chronic sarcoid myopathy.

The authors describe a patient with chronic sarcoid myopathy. Except for the presence of left posterior synechia, no other organ involvement was observed. Gallium-67 ((67)Ga) scintigraphy showed many intense nodular uptake areas in both the upper and lower extremities. Treatment with oral prednisolone 30 mg/day resulted in a marked improvement on (67)Ga scintigraphy. This case suggests that (67)Ga scintigraphy is useful for the differential diagnosis of systemic myopathies and also for monitoring the effect of glucocorticoid treatment.

Aged↗
PubMed2003

"All in one" cardiopulmonary bypass circuit for aortic surgery.

We devised an "all in one" cardiopulmonary bypass circuit for aortic surgery, and evaluated its efficacy and safety. The circuit consisted of a venous line, reservoir, single centrifugal pump, membrane oxygenator and arterial line bifurcated into two lines for systemic perfusion and selective branch perfusion. The perfusion volume was regulated by an occluder and measured by a flow sensor. A closed partial bypass was established using a shunt line bypassing the reservoir. We applied this circuit to 25 patients with aortic disease. Regulation of both the selective cerebral perfusion (SCP) and the selective branch perfusion was easily performed. There was neither stroke nor organ dysfunction postoperatively. There are some cases in which it is difficult to decide the necessity for SCP preoperatively; the use of this circuit may resolve this problem. This circuit can be easily and safely applied to any type of aortic surgery.

Adult↗
PubMed2003

Immunoglobulin G enzyme-linked immunosorbent assay using truncated nucleoproteins of Reston Ebola virus.

We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using partial recombinant nucleoproteins (rNP) of Reston Ebola virus (EBO-R) and Zaire Ebola virus (EBO-Z). We examined the reaction of 10 sera from cynomolgus macaques naturally infected with EBO-R to each of the partial rNP in the IgG ELISA. All the sera reacted to the C-terminal halves of the rNP of both EBO-R and EBO-Z. Most of the sera reacted to the RdeltaC (amino acid (aa) 360-739), and Rdelta6 (aa 451-551) and/or Rdelta8 (aa 631-739) at a higher dilution than to the corresponding truncated rNPs of EBO-Z. The results indicate that this IgG ELISA is useful for detecting EBO-R specific antibody, and may have a potential to discriminate EBO-R infection from other subtypes.

Animals↗
PubMed2002

Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein.

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP-55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins.

Administration, Oral↗
PubMed2001

Age-related changes in the localization of presenilin-1 in cynomolgus monkey brain.

Age-related changes in PS-1 localization were examined in the brains of 22 cynomolgus monkeys ranging in age from embryonic day 87 to 35 years. In embryonic monkey brains, anti-PS-1 antibody N12, which recognizes the PS-1 N-terminal fragment (Ntf) and holo protein, stained immature neuronal cells. In juvenile monkeys, N12 stained large pyramidal neurons, cerebral neocortical neurons, and cerebellar Purkinje's cells. Cytoplasmic staining of these cells was granular in appearance. In aged monkeys, N12 stained neurons in all layers of the neocortex. In contrast, regardless of the age of the animals examined, M5, an anti-PS-1 antibody that specifically recognizes only the PS-1 C-terminal fragment (Ctf), stained neurons in all layers of the neocortex and neurons in the cerebellum. M5 also stained neuropil and white matter, and in aged monkeys, M5 stained swollen neurites of mature senile plaques. Age-related changes in PS-1 expression were further examined using Western blot analysis of mitochondrial, myelin, microsomal, nuclear, synaptosomal, and cytosol fractions isolated from 10 monkey brains ranging in age from embryonic day 87 to 32 years. In all brains, Ntf and Ctf were expressed most abundantly in the microsome fraction. The amount of PS-1 in the nuclear fraction dramatically increased with age. We conclude that the transport of PS-1 diminished with age and that PS-1 fragments accumulated in endoplasmic reticulum (ER) associated with the nuclear membrane.

Aging↗
PubMed2001

Behavioral compensations in a positional learning and memory task by aged monkeys.

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.

Journal Article↗