Biomedical subjects

Y Tasaki

Publications and source records attributed to Y Tasaki.

At least 19 recordsLinked to original sources

PubMed2001

beta-amyloid deposits in transgenic mice expressing human beta-amyloid precursor protein have the same characteristics as those in Alzheimer's disease.

A transgenic mouse expressing the human beta-amyloid precursor protein with the "Swedish" mutation, Tg2576, was used to investigate the mechanism of amyloid-beta peptide (Abeta) deposition. We characterized Abeta deposits in the cerebral cortex biochemically and pathologically. A surface-enhanced laser desorption/ionization affinity mass spectrometric study using the 6E10 monoclonal antibody demonstrated that the major species of Abeta in a formic acid-extracted fraction of the cortex were Abeta(1-38), Abeta(1-40) and Abeta(1-42). Immunohistochemistry using antibodies to the carboxy-terminal epitopes of Abeta(1-40) and Abeta(1-42), as well as 6E10, showed that plaques containing Abeta(1-42) were more numerous than those containing Abeta(1-40) throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that Abeta(1-40) was preferentially located in the central part of the Abeta(1-42) positive plaques. Enzyme-linked immunosorbent assay measurements of Abeta(1-40) and Abeta(1-42) showed that Abeta(1-40) was several-fold more abundant than Abeta(1-42). From these data we suggest that Abeta(1-42) deposition may precede Abeta(1-40) deposition, while Abeta(1-40) begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of Abeta(1-40) corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and alpha-synuclein. Thus, Abeta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease.

Alzheimer Disease↗

PubMed2001

Induction and secretion of RNA-degrading enzymes by phosphate deficiency in Pholiota nameko.

Changes in activity of RNA-degrading enzyme and amounts of phosphorus in mycelia and culture filtrate during Pi-sufficient and -deficient cultures of Pholiota nameko were investigated. The results showed that the intracellular and extracellular activities are controlled by the Pi concentration in the medium. Moreover, the induction and secretion of RNA-degrading enzymes under the Pi-deficient condition were analyzed by activity staining.

Acid Phosphatase↗

PubMed2000

Is allantoin in serum and urine a useful indicator of exercise-induced oxidative stress in humans?

To assess whether allantoin levels in serum and urine are influenced by exhaustive and moderate exercise and whether allantoin is a useful indicator of exercise-induced oxidative stress in humans, we made subjects perform exhaustive and moderate (100% and 40% VO2max) cycling exercise and examined the levels of allantoin, thiobarbituric acid reactive substances (TBARS) and urate in serum and urine. Immediately after exercise at 100% VO2max, the serum allantoin/urate ratio was significantly elevated compared with the resting levels while the serum urate levels was significantly elevated 30 min after exercise. The serum TBARS levels did not increase significantly compared with the resting levels. Urinary allantoin excretion significantly increased during 60 min of recovery after exercise, however, urinary urate excretion decreased significantly during the same period. The urinary allantoin/urate ratio also rapidly increased during 60 min of recovery after exercise. Urinary TBARS excretion decreased during the first 60 min of the recovery period and thereafter significantly increased during the latter half of the recovery period. On the contrary, after 40% VO2max of exercise, no significant changes in the levels of urate, allantoin and TBARS in serum or urine were observed. These findings suggest that allantoin levels in serum and urine may reflect the extent of oxidative stress in vivo and that the allantoin which appeared following exercise may have originated not from urate formed as a result of exercise but from urate that previously existed in the body. Furthermore, these findings support the view that allantoin in serum and urine is a more sensitive and reliable indicator of in vivo oxidative stress than lipid peroxidation products measured as TBARS.

Adult↗

PubMed2000

Emphysematous cystitis following brain contusion.

Emphysematous cystitis is a rare disorder most commonly seen in patients with urinary tract infection and diabetes mellitus. We present a nondiabetic case of a 46-year-old woman with this entity following brain contusion.

Brain Injuries↗

PubMed1999

Chemokine PARC gene (SCYA18) generated by fusion of two MIP-1alpha/LD78alpha-like genes.

Two loci in the human genome, chromosomes 4q12-q21 and 17q11.2, contain clusters of CXC and CC chemokine subfamily genes, respectively. Since mice appear to contain fewer chemokine genes than humans, numerous gene duplications might have occurred in each locus of the human genome. Here we describe the genomic organization of the human pulmonary and activation-regulated CC chemokine (PARC), also known as DC-CK1 and AMAC-1. Despite high sequence similarity to a CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha)/LD78alpha, PARC is chemotactic for lymphocytes and not for monocytes and does not share its receptor with MIP-1alpha. Analyses of the BAC clones containing the human PARC gene indicated that the gene is located most closely to MIP-1alpha (HGMW-approved symbol SCYA3) and MIP-1beta (HGMW-approved symbol SCYA4) on chromosome 17q11.2. Dot-plot comparison suggested that the PARC gene had been generated by fusion of two MIP-1alpha-like genes with deletion and selective usage of exons. Base changes accumulated before and after the fusion might have adapted the gene to a new function. Since there are variably duplicated copies of the MIP-1alpha gene called LD78beta (HGMW-approved symbol SCYA3L) in the vicinity of the MIP-1alpha gene, the locus surrounding the MIP-1alpha gene seems to be a "hot spring" that continuously produces new family genes. This evidence provides a new model, duplication and fusion, of the molecular basis for diversity within a gene family.

Animals↗

PubMed1998

Deprenyl decreases an endogenous parkinsonism-inducing compound, 1-benzyl-1,2,3,4-tetrahydroisoquinoline in mice: in vivo and in vitro studies.

We examined the effect of deprenyl, a promising drug for the therapy of Parkinson's disease on the formation of a parkinsonism-inducing compound, 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ). The 1BnTIQ content was significantly decreased in the brain of deprenyl-treated mouse in vivo, and deprenyl also inhibited 1BnTIQ formation from phenethylamine by a mouse brain homogenate supernatant in vitro. In vivo, the content of a parkinsonism-preventing compound, 1-methyl-1,2,3, 4-tetrahydroisoquinoline (1MeTIQ) was slightly increased in mice injected with deprenyl. The marked decrease of the ratio of 1BnTIQ to 1MeTIQ might play a role in the clinical effect of deprenyl.

Animals↗

PubMed1998

Expansion of venous flaps: an experimental study in rats.

In this study, the effects of controlled tissue expansion on the survival of unipedicled venous flaps were investigated in rats. In three groups of Lewis rats, a 3 x 6 cm unipedicled Lateral thoracic venous flap was studied with group 1 as control group (n = 30) without any manipulation, group 2 (n = 30) where an expander was introduced under the flap area but was not expanded and group 3 (n = 30) in which a 40 ml expander was introduced under the flap area and was expanded over a period of 10 days. Observations included gross and histological examination, reverse microangiography, reverse flow resistance and percentage of survival of flaps. Group 3 (expanded) showed more angiogenesis, a better delineation on microangiography, lower reverse flow resistance and higher survival rates as compared to group 2 (non-expanded). In the control group the survival rate of flaps was the poorest and the flaps showed higher rates of reverse flow resistance. Microangiography was not successful in the control group. In a pilot project prior to this experiment microscopic examination of the Lateral thoracic vein in 10 Lewis rats had confirmed the presence of two or three valves in this vein.

Angiography↗

PubMed1998

Venous drainage through bone marrow after replantation: an experimental study.

Venous drainage is vital for successful replantation, but it is not always possible to reconstruct because of missing or damaged veins. We devised an experimental model to study venous drainage through bone marrow while the new subcutaneous venous system regenerated. Adult male Wistar rats were placed into three groups. Group A rats had their hindlimbs amputated at the lower leg, but the tibia and sural and saphenous artery connections were preserved. Group B rats were prepared the same as Group A, except that a step-cut osteotomy was performed in the tibia. The bone ends were then realigned and kept in place with stainless steel wire. Group C rats were prepared the same as Group B, except that the ends of the bone were not aligned. All unoperated limbs served as controls for evaluations of blood flow. Experimental limbs were evaluated for skin colour and viability, blood flow and dye injection. Skin colour was investigated daily. Blood flow was measured postoperatively during three phases: immediate (up to 1 h), early (from 1 h to 24 h), and late (from 1 day to 7 days after operation). Survival of limbs varied in Groups A and B, while all limbs in Group C necrosed by day 7. Blood flow was returning to near control (normal) levels by day 7 in Group A and B limbs. India ink was observed in the medullary cavity at day 7. After replantation, bone marrow plays a critical role in venous drainage until the subcutaneous venous drainage system regenerates.

Animals↗

PubMed1998

Testis sparing surgery for infantile synchronous bilateral teratoma of the testis.

We report a rare case of infantile synchronous bilateral testicular teratoma treated by testis sparing surgery. Preoperative ultrasonography, tumor marker status and intraoperative findings were suggestive of benign neoplasia. Under these circumstances we performed high orchiectomy for the left testis and testis sparing surgery for the right. Surgical treatment of teratoma in childhood is controversial, especially when it occurs bilaterally. In this report we discuss testis sparing surgery as the treatment for this disease.

Biopsy↗

PubMed1997

The effects of tissue expansion on the hemodynamic and survival characteristics of reverse-flow island flaps: an experimental study in rabbits.

The effects of tissue expansion on the hemodynamic and survival characteristics of reverse-flow island skin flaps were investigated in New Zealand White rabbits. The animals were divided into 3 groups of 15: group I (control) had no surgery prior to flap elevation, group II (nonexpansion) had a noninflated expander, and group III (expansion) had an inflated expander of 80 ml. After 3 weeks of expansion, a reverse-flow island flap based on the distal saphenous pedicle was elevated. A series of hemodynamic studies was performed to test reverse venous flow--in particular, valve competence. Besides observing the reverse flow under an operating microscope, the changes in the intravenous pressure were measured at 0, 5, 15, 30, 60, and 120 minutes after flap elevation. Moreover, reverse-flow resistance (RFR) was measured in each group to test the competence of venous valves. At each time interval, the values of intravenous pressure were significantly lower (p < 0.01) in group III than in the groups I and II. However there was no statistically significant difference between group I and group II. The RFR was measured as 126.7 +/- 33.52 mmHg in group I, 59.3 +/- 29.86 mmHg in group II (p < 0.01), and 25.1 +/- 7.68 mmHg in group III (p < 0.01). Ten days after flap elevation the mean survival of group III (100%) was statistically higher than that of group I (57.4 +/- 18.3%; p < 0.01) and group II (81.6 +/- 12.8%; p < 0.05). These findings simply suggest that controlled tissue expansion improves retrograde venous drainage and increases the survival of reverse-flow island flaps in rabbits. Abnormal dilatation of the venous tree and incompetence of the venous valves seem to be the main factors in explaining the decrease in the values of RFR and intravenous pressure in the expanded flaps. The potential mechanisms to explain the effects of tissue expansion, and the clinical implications are discussed.

Animals↗

PubMed1997

Three approaches for laparoscopic unroofing of simple and complicated renal cysts.

We report 2 cases of simple renal cysts which were marsupialized with 2 laparoscopic approaches involving either transperitoneal, with reflection of the colon medially or dissection through the mesocolon, and a case of a multilocular renal cyst which was treated by the retroperitoneal approach. Although laparoscopic unroofing of a renal cyst is a safe and effective alternative to open surgical techniques, the transperitoneal approach should only be used for simple renal cysts. The retroperitoneal approach for complicated renal cysts may be indicated if preoperative examinations exclude the possibility of malignancy.

Aged↗

PubMed1996

Chronic administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine in the brain, induces parkinsonism in a primate.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1Bn TIQHCl) (22 mg/kg per day) was subcutaneously injected into a monkey, Macaca fascicularis for 66 days to investigate its acute and chronic effects Parkinsonism like motor symptoms appeared, and the acute toxicity was stronger than the chronic toxicity. This result suggested that 1BnTIQ may induce parkinsonism in humans. 1BnTIQ content in various regions of the monkey brain was determine by the gas chromatography-selected ion-monitoring method, but no significant variation was found.

Animals↗

PubMed1996

Low levels of mRNA for dopamine D4 receptor in human cerebral cortex and striatum.

Significant densities of mRNA for the dopamine D4 receptor in cerebral cortex, particularly in frontal lobe, have been reported in rats and monkeys, supporting the D4 hypothesis in the pathology of schizophrenia. Using northern blot analysis and the competitive reverse transcription-polymerase chain reaction (RT-PCR) method, we determined the relative levels of D4 mRNA in human brain regions to clarify whether the cortical level is also higher in humans. Northern blot analysis revealed an unexpected profile of D4 mRNA in the brain. The detected mRNA size, 1.5 kb, was quite different from the 5.3 kb reported in human neuroblastoma SK-N-MC cells. Higher levels of D4 mRNA were detected not only in the mesolimbic system but also in the corpus callosum, spinal cord, medulla, and subthalamic nucleus. It was surprising that in the cerebral cortex regions as well as the striatum, D4 mRNA was hardly detected. The competitive RT-PCR revealed these relative densities to be at least three orders of magnitude lower than that of the striatal D2 receptor. Our results demonstrate a remarkable difference in cortical D4 mRNA density in humans compared with that in rats and monkeys. Furthermore, the mRNA distribution suggests that the higher density of D4-like binding sites reported recently in normal human striatum is not due to the D4 receptor.

Blotting, Northern↗

PubMed1996

In vitro pharmacological profile of YM-43611, a novel D2-like receptor antagonist with high affinity and selectivity for dopamine D3 and D4 receptors.

1. We investigated some neurochemical properties of a novel benzamide, YM-43611, [(S)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-cyclopropylcarbonylamino+ ++-2- methoxybenzamide] in comparison with putative D2-like receptor antagonists using both rat and human cloned dopamine D2-like receptors in vitro. 2. Receptor binding studies revealed that YM-43611 had appropriately potent affinities for both rat and human D2-like receptors, with moderate selectivity for D3 receptors and high selectivity for D4 receptors over D2 receptors (Ki values (nM) for rat receptors: D2, 165; D3, 35.5; D4, 1.85, and for human receptors: D2, 42.9; D3, 11.2; D4, 2.10). 3. YM-43611 displayed weak or negligible affinity for other neurotransmitter receptors, namely D1, D5, alpha(1), alpha(2), beta, 5-HT1A, 5-HT2A, 5-HT3, H1, M1 and M2 receptors. 4. Dopamine stimulated low-Km GTPase activity on membranes from Chinese hamster ovary (CHO) cells expressing the human D2-like receptor subtype. This response to dopamine of low-Km GTPase activity was inhibited by use of putative D2-like receptor antagonists. YM-43611 showed a moderate selectivity for D3 receptors (Ki = 45.5 nM) and a high selectivity for D4 receptors (Ki = 3.28 nM) over D2 receptors (Ki = 70.6 nM). 5. Dopamine inhibited forskolin-stimulated adenylate cyclase in intact CHO cells expressing the human D2-like receptor subtype. YM-43611 shifted the inhibition curve of dopamine on respective D2-like receptor subtype-mediated cyclic AMP formation to the right in a parallel fashion, showing a pA2 value of 7.42 (38.1 nM) for D2 receptors, a pKB value of 8.06 (8.68 nM) for D3 receptors, and a pA2 value of 8.42 (3.77 nM) for D4 receptors. 6. YM-43611 but not the other D2-like receptor antagonists exhibited good selectivity with respect to dual antagonism for D3 and D4 receptors in both receptor binding and functional assays. 7. These results indicate that YM-43611 is a novel D2-like receptor antagonist with high potency and selectivity for both D3 and D4 receptors. YM-43611 is therefore expected to be valuable in exploration of the physiological role of D3 and D4 receptors.

Animals↗

PubMed1995

Differential effects of [3H]nemonapride and [3H]spiperone binding on human dopamine D4 receptors.

We compared some binding parameters of [3H]nemonapride and [3H]spiperone in human dopamine D4 (hD4) receptors with three different numbers of tandem repeat units. Although both of the radioligands showed similar affinity constants for each hD4 receptor variant, the maximal number of binding sites labeled by [3H]nemonapride was approximately 1.35-fold higher than that by [3H]-spiperone for all variants. Estimated Ki values for the inhibition of [3H]nemonapride binding by a series of dopaminergic ligands were highly correlated to respective values obtained for the inhibition of [3H]spiperone binding to each hD4 receptor. These results suggest that the hD4 receptor, as shown for the D2 receptor, may exist in multiple molecular forms as a monomer-dimer equilibria, and that [3H]spiperone may discriminate in the multiple molecular forms.

Benzamides↗

PubMed1995

Polymorphic tandem repeats in dopamine D4 receptor are spread over primate species.

The human dopamine D4 receptor has polymorphic tandem repeats in the third cytoplasmic loop. However, these repeats are not present in the rat counterpart. To determine whether the tandem repeats are specific to humans or not, we analyzed genomic DNA sequences for the D4 receptor of six primate species (human, chimpanzee, gorilla, orangutan, macaque, marmoset). Sequencing data revealed that all primates have the 48-bp tandem repeats in the D4 receptor gene. This finding suggests that these repeats originated before the separation of the New World monkey lineage from the Old World monkey and ape-human lineages.

Amino Acid Sequence↗

PubMed1995

Full-length cDNA cloning and distribution of human dopamine D4 receptor.

Dopamine D4 receptor is the focus of interest in terms of pharmacological profile and possible relation to the disease. Using poly A+RNA from human retina as a template, we succeeded in cloning of full-length cDNA of the human dopamine D4 receptor by improved reverse transcription-polymerase chain reaction (RT-PCR). From the RT-PCR products, two polymorphic variants which had two and four tandem repeats in the putative third cytoplasmic loop were obtained. Transient expression of the full-length cDNA in COS-1 cells produced [3H]spiperone binding sites with a high affinity. These results confirmed the existence of the D4 receptor mRNA containing a different number of polymorphic tandem repeats in native human tissues. The RT-PCR method demonstrated the restricted distribution of the D4 mRNA in human tissues and brain regions. The mRNA was detected at the highest level in the retina, followed by the brain, placenta, and kidney. Among brain regions, relatively low levels for mRNA of the human D4 receptor were observed in the nigrostriatal pathway compared with the mesolimbic system. The distribution of the mRNA in human brain suggests that the D4 receptor plays a different role in the central nervous system compared with the D2 receptor.

Base Sequence↗

PubMed1995

1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was detected as a novel endogenous amine in mouse brain and parkinsonian CSF by using the gas chromatography-selected ion-monitoring method. The level of 1BnTIQ was very high in CSF of some parkinsonian patients compared with that of controls with other neurological diseases, the mean value being three times higher (parkinsonians: 1.17 +/- 0.35 ng/ml of CSF, n = 18; vs. controls: 0.40 +/- 0.10 ng/ml of CSF, n = 11; mean +/- SEM, not significantly different). The pole test, a toxicological examination to evaluate behavior abnormalities related to Parkinson's disease, was used to examine the pharmacological effect of 1BnTIQ in mice. Repeated administration of 1BnTIQ induced behavior abnormalities, which pretreatment with 1-methyl-1,2,3,4-tetrahydroisoquinoline could prevent. We suggest that 1BnTIQ may be related to the idiopathic Parkinson's disease.

Animals↗