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Biomedical subjects

K Yanai

Publications and source records attributed to K Yanai.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Recurrent thymic carcinoid tumor with multiple endocrine neoplasia syndrome--a case report].

A 55-year-old male with multiple endocrine neoplasia syndrome accompanied by hyperparathyroidism and hypergastrinemia was admitted because of local recurrence of thymic carcinoid tumor and a parathyroid adenoma. The recurrent thymic carcinoid tumor replaced anterior mediastinum, invaded brachiocephalic vein and superior vena cava, a disseminated nodule was found at pericardium. After induction chemotherapy using carboplatin and etoposide the operation was performed. The parathyroid tumor and recurrent thymic carcinoid tumor were removed completely together with brachiocephalic vein, superior vena cava, pericardium and anterior chest wall. Superior vena cava was replaced with synthetic graft and chest wall was reconstructed. The patient is alive and well 22 months after surgery without recurrence. Immunohistochemistry of removed specimens revealed parathormone and gastrin secreted from the parathyroid adenoma but not from the carcinoid tumor. Careful survey of systemic endocrine organs is necessary in case of thymic carcinoid tumor. Aggressive surgery in locally recurrent thymic carcinoid without distant metastasis must be considered.

Carcinoid Tumor↗
PubMed1996

Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors.

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.

Animals↗
PubMed1996

Positron emission tomography study of the alterations in brain distribution of [11C]methamphetamine in methamphetamine-sensitized dog.

We newly prepared a MAP-sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP-sensitized dog using PET. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP-sensitized brain indicates that subchronic MAP administration causes some functional change in the uptake site of MAP. The pharmacokinetic change may, in part, account for behavioral sensitization.

Animals↗
PubMed1996

A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene.

The promoter of the human angiotensinogen (hAG) gene functioned in its own core promoter context but not when replaced with simian virus 40 (SV40) core promoter, suggesting the presence of a transcriptionally important cis-acting sequence. Electrophoretic mobility shift assays demonstrated that a ubiquitously expressed nuclear factor, AGCF1, bound to AGCE1 (hAG core promoter element 1; positions -25 to -1) located between the TATA box and transcription initiation site. Substitution mutation in AGCE1 which disrupted AGCF1 binding affected the promoter activity more severely than a nonsense mutation of the hAG TATA sequences did. When AGCE1 was placed at the downstream of SV40 core promoter, the responsiveness to hAG upstream region was significantly restored. Furthermore, mutation and in vivo competition experiments suggested that AGCF1 acts as a critical regulator of hAG transcription by mediating the activity of the hAG upstream and downstream enhancer elements. DNase I footprinting and UV cross-linking analyses showed that AGCF1 with apparent molecular masses of 31, 33, and 43 kDa as the components protected the region from -26 to -9 which partially overlapped with the TATA box consensus sequences. These findings indicate that AGCE1 in addition to the TATA box plays a key role in mediating the hAG regulatory elements.

Angiotensinogen↗
PubMed1996

Behavioral studies on rats with transient cerebral ischemia induced by occlusion of the middle cerebral artery.

The behavioral effects of transient cerebral ischemia in adult Wistar rats were studied. In Experiment 1, rats were subjected to 90-min occlusion of the unilateral, left or right, middle cerebral artery (MCA) followed by recirculation. The locomotor activity had not changed 3 and 30 days after the occlusion, except that the number of rearing was significantly decreased by left MCA occlusion. Rats were examined in a radial maze system for learning and memory ability during 4 weeks from the 3rd day after ischemia (the 3rd day was counted as day 1 of the experiment). Maze performance was slightly disturbed due to focal brain damage by MCA occlusion, but the disturbance was statistically significant only on days 6, 11, and 15 in the right occlusion. In Experiment 2, rats were trained to master a radial maze task completely for 4 weeks, and then subjected to transient unilateral (right) ischemia as described above. These rats showed an increase in incorrect entry in the radial maze task from day 4 to day 14. However, on day 21, the number of incorrect entry decreased to the control level of the sham-operated group. The numbers of correct choice were inversely related with those of incorrect entry, though slightly blunted. Coincidentally, the time required to solve the maze task was also prolonged from day 4 to day 14, but returned to the control time on day 21. These results suggest that unilateral ischemia transiently suppresses both acquiring radial maze performance and maintenance of learned performance and that it is a good model for studying human focal cerebral ischemia.

Adult↗
PubMed1996

Effects of unilateral vagotomy on nitric oxide synthase and histamine H3 receptors in the rat dorsal vagal complex.

Nitric oxide synthase (NOS) and histamine H3 receptors are both markedly increased by neuronal injuries. To examine whether peripheral axotomy produced differential changes in NOS and H3 receptors, both NOS and H3 receptors were measured in the dorsal vagal complex after unilateral vagotomy. The presence of NOS-positive neurons was examined using both NADPH-diaphorase histochemistry and neuronal NOS-immunohistochemistry in rats vagotomized at the mid-cervical level. NADPH-diaphorase activity and NOS-immunoreactivity were markedly enhanced on the dorsal motor nucleus of the vagus (DMX) and in the ambiguous nucleus at the denervated side. Intraperitoneal injection of NOS inhibitors, N omega-nitro-L-arginine (10 mg/kg) or dexamethasone (0.5 mg/kg) attenuated the increase in NADPH-diaphorase activity. Glial fibrillary acidic protein (GFAP) was similarly induced 2 weeks after vagotomy in the vagal complex and surrounding area. Histamine H3 receptors in the vagal complex were visualized with [3H]N alpha-methylhistamine. The ligand-labeled H3 receptors were mainly located at the nucleus of the solitary tract (NST). The densities of H3 receptors did not change in the NST after unilateral vagotomy. These results suggest that peripheral axotomy such as mid-cervical vagotomy preferentially induces NOS in damaged neurons without affecting the level of H3 receptors.

Animals↗
PubMed1996

The effect of dopamine D1 receptor stimulation on the up-regulation of histamine H3-receptors following destruction of the ascending dopaminergic neurones.

1. The binding of [3H]-(R)alpha-methylhistamine and [3H]-N alpha-methylhistamine to histamine H3-receptors, [3H]-SCH23390 to dopamine D1-receptors, and [3H]-YM09151-2 to dopamine D2-receptors was investigated by quantitative receptor autoradiography in the rat brain following 6-hydroxydopamine injection into the substantia nigra. 2. The levels of [3H]-(R)alpha-methylhistamine binding sites in the denervated striatum and substantia nigra were significantly higher than those in the contralateral side from 1 week to 12 weeks after nigral lesions. The H3-receptor binding was maximal at 3 weeks after nigral lesions and maintained until 12 weeks. 3. The increased number of histamine H3-receptors was decreased to the level of the contralateral side by chronic treatment with a selective dopamine D1 agonist, SKF38393, but not modified by a selective dopamine D2 agonist, quinpirole. 4. Dopamine D1- and D2-receptors in the striatum were similarly up-regulated after unilateral nigral lesion. On the other hand, the number of dopamine D2-receptors in the substantia nigra was markedly decreased after administration of 6-hydroxydopamine. 5. The treatment with (S)alpha-fluoromethylhistidine increased the H3-receptor binding in both the ipsilateral and contralateral sides. As a result, the magnitude of the ratio of the H3-receptor binding between ipsilateral and contralateral sides was partially attenuated by treatment with (S)-alpha-fluoromethylhistidine. 6. These results strongly suggest that the expression of histamine H3-receptors in the striatum and substantia nigra is influenced through D1-receptors by tonic nigrostriatal dopaminergic inputs.

Animals↗
PubMed1996

Cloning and characterization of the Rhizopus niveus leu1 gene and its use for homologous transformation.

The Rhizopus niveus leul gene was cloned using a 2-kb HindIII fragment of the leuA gene of Mucor circinelloides as a hybridization probe. The coding region of this gene comprises 1890 bp that encode a putative protein of 630 amino acids. The predicted amino acid sequence is similar to those of other alpha-isopropylmalate isomerases (alpha-IPMIs), showing 79.4%, 71.7%, and 60.6% identity with the Mucor circinelloides LeuA, Phycomyces blaskesleeanus Leu1, and Ustilago maydis Leu1, respectively. The vector pRN1, which contains a 3.7-kb BamHI-SacI fragment of the R. niveus leul gene, could complement leucine auxotrophy of R. niveus M-37 (leu1-), suggesting that the gene codes for alpha-IPMI of R. niveus. Both the transformation frequency and mitotic stability with pRN1 were higher than those with leuA gene-containing vectors. It was found by using the leul gene that the autonomously replicating sequence (ARS) of P. blakesleeanus partially functions as an ARS in R. niveus.

Amino Acid Sequence↗
PubMed1996

The integrative transformation of Pleurotus ostreatus using bialaphos resistance as a dominant selectable marker.

A plasmid pLC-bar containing the bialaphos resistance gene derived from Streptomyces hygroscopicus between the Lentinus edodes ras gene promoter and priA gene terminator was constructed. When protoplasts of Pleurotus ostreatus were mixed with the plasmid DNA in the presence of polyethylene glycol and CaCl2, bialaphos-resistant colonies were obtained. This indicated that transformation was successful. Southern blot analysis of total DNAs from transformants showed that the introduced plasmid DNA was integrated into the host chromosome and partly rearranged. A plasmid, pLC-GUS, containing the Escherichia coli beta-glucuronidase (GUS) gene under the control of the L. edodes ras gene promoter and priA gene terminator was constructed and introduced into protoplasts of P. ostreatus with pLC-bar by co-transformation. Two of 5 transformants obtained as bialaphos-resistant colonies showed two to twenty times higher specific activity of GUS than the recipient. Southern blot analysis of total DNAs from transformants indicated the presence of the GUS gene only in the two transformants. These results indicated that co-transformation of P. ostreatus was successful, and that the GUS gene was expressed in P. ostreatus. This transformation system will enable us to breed commercial strains of P. ostreatus at the molecular level.

DNA, Fungal↗
PubMed1996

Analysis of plasma metabolites during human PET-studies with three receptor ligands, [11C]YM-09151-2, [11C]doxepin and [11C]pyrilamine.

Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D2 ligand [11C]YM-09151-2 as well as the histamine H1 ligands [11C]doxepin and [11C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [11C]YM-09151-2 and [11C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [11C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [11C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement.

Adult↗
PubMed1996

[Regional distribution of the muscarinic cholinergic receptor in the human brain studied with 11C-benztropine and PET using an anatomical standardization technique].

We measured regional distribution of the muscarinic cholinergic receptor in the normal human brain with 11C-benztropine (BZT) and positron emission tomography (PET) using an anatomical standardization technique. Seven normal volunteers who gave informed consents were involved in this study. Immediately after intravenous injection of 11C-BZT into the subjects, we started dynamic PET scanning and serial frequent arterial blood sampling. Analyses of plasma metabolites were also performed at selected time points and plasma time activity curves (TAC) of unmetabolized ligand were generated. From these PET and TAC data, we obtained Patlak plot slope calculation images. Using the HBA (human brain atlas) system, the Patlak plot slope calculation image of each subject was transformed into the shape of the standard brain. Mean and standard deviation (SD) calculation images were generated from those anatomically standardized images. On these mean and SD images, we placed regions of interest which were previously outlined on a MR image of the standard brain. From those data, we found the highest receptor distribution in the striatum and occipital cortex, as well as high distribution in the frontal, parietal, and temporal cortices, which were consistent with previous reports. These results suggested that anatomical standardization of PET receptor images with 11C-BZT will be useful for delineating the physiological or pathological alterations of the muscarinic cholinergic receptor in the human brain.

Adolescent↗
PubMed1995

Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography.

The postnatal ontogenetic development of the histamine receptor subtypes was studied in rat brain by quantitative receptor autoradiography with highly sensitive imaging plates. H1 receptor binding sites labeled with [3H]pyrilamine were detected on postnatal day 2 (P2) and increased very slowly until P9, and then rapidly reaching the adult levels in the hypothalamus, hippocampus, and amygdala by P16. The densities of H1 receptor binding sites in the cortex, striatum, thalamus, and substantia nigra were relatively low during development. H3 receptor binding sites labeled with [3H](R) alpha-methylhistamine were not detectable until P9. On P9, their density was higher in the substantia nigra than in other regions. Subsequently, H3 receptor binding increased, reaching the adult levels in the substantia nigra on P16 and in the other regions on P23. The histamine concentration was initially very high, but decreased to the adult level by P16. On the contrary, the activity of L-histidine decarboxylase of whole brain tissue was low on P5, and increased markedly from P16 to P23, to the adult level on P30. Administration of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of L-histidine decarboxylase (HDC), significantly decreased both the HDC activity and histamine concentration during postnatal development. FMH treatment did not change H1 receptor binding in any brain region, but significantly increased H3 receptors in the substantia nigra and striatum on P23. Unilateral injection of 6-hydroxydopamine into the striatum on P2 resulted in up-regulation of H3 receptor binding sites in the dorsomedial (11%) and dorsolateral (18%) regions of the striatum and substantia nigra (31%) on P23, but no change in the H3 receptor density in the nucleus accumbens or frontal cortex on P11 and P23. These results demonstrate that the developmental patterns of H1 and H3 receptors are heterogeneous and independent of each other. There are marked mismatches of presynaptic and postsynaptic markers of the histaminergic neuron system as in other aminergic systems.

Aging↗
PubMed1995

Analysis of the 3-phosphoglycerate kinase 2 promoter in Rhizopus niveus.

Promoter analysis was performed on the Rhizopus niveus 3-phosphoglycerate kinase 2-encoding gene (pgk2), one of the two pgk genes (pgk1 and pgk2) from this filamentous fungus sequenced so far. Deletion mutants of the promoter region were fused to the Escherichia coli uidA gene (which codes for beta-glucuronidase; GUS), and introduced into R. niveus to measure the intracellular GUS activities of the transformants. Deletion of the sequence between nt -174 to -133 (numbers indicate the position from the putative translation start codon) caused a significant decrease in the ratio of the GUS activity of the transformant cultured in glucose medium compared to that in glycerol medium. In this region, a 21-nt sequence which is well conserved between pgk1 and pgk2 is present. When it was inserted into the promoter region of the uninducible gene encoding RNase Rh of R. niveus, ligated in front of uidA and introduced into R. niveus, the GUS activity of the transformant was greatly induced by glucose, but less by glycerol. We therefore suggest that the 21-nt sequence is a glucose-inducible transcriptional activator of R. niveus. This is the first report on a transcriptional activator in zygomycetes.

Base Sequence↗
PubMed1995

Prion disease with 144 base pair insertion in a Japanese family line.

We describe an insert mutation in the prion protein (PrP) gene in a Japanese family line that encodes six octapeptide repeats. This is the second report to date of an inherited prion disease with a 144-base pair insertion, although the order of the repeat sequences differ from that reported for the disease in an English family line. The clinical features, like those of the English patients, were characterized by a slowly progressive generalized dementia with some neurological signs and cortical focal symptoms. Postmortem examination disclosed diffuse atrophy of cerebral gray matter and the cerebellar cortex; histologically, there were marked patchy and regional neuronal loss with astrocytosis in the frontal cortex, amygdala and hippocampus and PrP-immunoreactive plaques in the molecular layer of the cerebellum. These plaques were different from typical kuru plaques. The prion disease in the present Japanese family line is compared with that in the English family line.

Adult↗
PubMed1995

Cloning of the Rhizopus niveus pyr4 gene and its use for the transformation of Rhizopus delemar.

We have cloned a pyr4 gene encoding orotidine-5'-monophosphate decarboxylase of the filamentous fungus Rhizopus niveus. The pyr4 gene of R. nivens has an open reading frame composed of 265 amino-acid residues and has two putative introns. We have also isolated a pyr4 mutant of Rhizopus delemar from 5-fluoroorotic acid-resistant mutants and transformed it with the pyr4 gene of R. niveus as a selectable marker. Introduced DNA was integrated into the chromosome in a multiple tandem array. The mitotic stability of the introduced DNA was increased by a repeated sporulation process. The expression of the Escherichia coli beta-glucuronidase gene in R. delemar was successfully obtained under the control of the pgk2 gene promoter of R. niveus by co-transformation with the pyr4 gene.

Amino Acid Sequence↗
PubMed1995

Effects of thioperamide, a histamine H3 antagonist, on the step-through passive avoidance response and histidine decarboxylase activity in senescence-accelerated mice.

The effect of thioperamide, a histamine H3 receptor antagonist, on learning and memory was studied in the senescence-accelerated mice-prone strain (SAM-P/8) and normal-rate aging strain (SAM-R/1). In a passive avoidance test, SAM-P/8 mice of 12 months showed significant impairment of learning and memory compared with SAM-R/1 mice of the same age. Thioperamide significantly improved the response latency in SAM-P/8 mice when injected intraperitoneally at a dose of 15 mg/kg. The histidine decarboxylase (HDC) activity in the forebrain was significantly lower in SAM-P/8 mice than in SAM-R/1 mice. Thioperamide administration significantly potentiated HDC activity in the forebrain of SAM-P/8 mice as well as improving learning and memory. These results suggest that central histaminergic neurons may be involved in learning and memory impairment of SAM-P/8 mice, although other possibilities are not ruled out.

Aging↗
PubMed1995

Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by positron emission tomography.

1. Histamine H1 receptor occupancy in the human brain was measured in 20 healthy young men by positron emission tomography (PET) using [11C]-doxepin. 2. (+)-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Intravenous administration of 5 mg (+)-chlorpheniramine almost completely abolished the binding of [11C]-doxepin to H1 receptors (H1 receptor occupancy: 98.2 +/- 1.2%). 3. Terfenadine, a nonsedative antihistamine, occupied 17.2 +/- 14.2% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 60 mg. 4. There was no correlation between H1 receptor occupancy by terfenadine and the plasma concentration of the active acid metabolite of terfenadine in each subject. 5. PET data on human brain were essentially compatible with those on H1 receptor occupancy in guinea-pig brain determined by in vivo binding techniques, although for the same H1 receptor occupancy the dose was less in human subjects than in guinea-pigs. 6. The PET studies demonstrated the usefulness of measuring H1 receptor occupancy with classical and second-generation antihistamines in human brain to estimate their unwanted side effects such as sedation and drowsiness quantitatively.

Administration, Oral↗