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Biomedical subjects

T Kawaguchi

Publications and source records attributed to T Kawaguchi.

At least 181 records · Page 10Linked to original sources
PubMed1997

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs.

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Adrenomedullin↗
PubMed1997

DAX-1 gene mutations and deletions in Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

Abnormality of the DAX-1 gene accounts for many instances of congenital adrenal hypoplasia. In the present study, we performed molecular genetic analysis of DAX-1 in 4 unrelated Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. A double-point mutation for V126M and W171X was identified in 1 family and a complex de novo insertion-deletion mutation was identified in a second. The DAX-1 gene was entirely deleted in a 3rd patient as well as in a 4th with the additional feature of glycerol kinase deficiency.

Adolescent↗
PubMed1997

Pubertal changes in testicular 3 beta-hydroxysteroid dehydrogenase activity in a male with classical 3 beta-hydroxysteroid dehydrogenase deficiency showing spontaneous secondary sexual maturation.

Males with classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency manifest appropriate secondary sexual maturation with an elevation in serum testosterone levels at pubertal age. To define the origin of serum testosterone, we evaluated a male patient with classical 3 beta-HSD who showed pubertal development. High values of testosterone and a ratio of delta(5) to delta(4) steroids in the spermatic vein indicated direct production of considerable amounts of testosterone and a persistent defect of 3 beta-HSD activity in the gonad. Immunohistochemical analysis showed distinct immunoreactivity in the Leydig cells of the patient. The patient was homozygous for a nonsense mutation in the type-II 3 beta-HSD gene. We propose that gonadal type-I 3 beta-HSD could be expressed by gonadotropin stimulation at pubertal age, and delta(4)-steroid precursors would convert to testosterone.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Synergistic effect of nitric oxide and vasoactive intestinal peptide on bronchoprotection against histamine in anesthetized guinea pigs.

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.

Anesthesia↗
PubMed1997

Inhibition of 5'-deoxy-5-fluorouridine phosphorolysis by acyclothymidine in tumor cell homogenates.

The inhibitory effect of acyclothymidine[AcyT, 5-methyl-1-(2'-hydroxyethoxymethyl) uracil], a potent pyrimidine nucleoside phosphorylase (PyNPase) inhibitor, on 5'-deoxy-5-fluorouridine (5'-DFUR) phosphorolysis in human and mouse tumor cell homogenates was measured. Competitive inhibition was observed in MKN-74 and Lewis lung carcinoma (LLC), whereas non-competitive inhibition was observed in HeLa. The strength of the inhibitory effect by AcyT showed the following pattern: HeLa < human normal intestine < mouse normal intestine < Colon 26 < LLC < MKN-74 < DLD-1. From the kinetic parameter obtained, we simulated the inhibitory effect of AcyT on 5'-DFUR phosphorolysis in tumor cells and the intestine. These data indicated that AcyT was more sensitive in normal mouse intestine than in Colon 26 and LLC, and that orally administered AcyT can reduce the intestinal toxicity of 5'-DFUR without reducing the antitumor effect in the mouse. The present finding may have an important implication for attempts to introduce AcyT, a potent PyNPase inhibitor, into the clinic.

Animals↗
PubMed1997

Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines.

Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines were synthesized in a search for compounds with potent antitumor activity and low toxicity. Some compounds exhibited more potent antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'-methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26, and Lewis lung carcinoma.

Animals↗
PubMed1997

Systemic sclerosis associated with diabetes insipidus.

A rare case of systemic sclerosis that preceded the development of diabetes insipidus is reported. This 25-year-old man presented with Raynaud's phenomenon and ulceration of the tip of the right thumb. The diagnosis of systemic sclerosis was based on findings of proximal scleroderma, sclerodactyly, serological abnormalities, and skin abnormalities verified histologically. Partial central diabetes insipidus was later diagnosed after the sudden appearance of polyuria and polydipsia. Coexistence of systemic sclerosis with diabetes insipidus suggests that diabetes insipidus in this patient might have occurred via an autoimmune mechanism.

Adult↗
PubMed1997

Short-latency somatosensory evoked potentials in patients with brain stem tumor: study of N20 and N18 potentials.

Short-latency somatosensory evoked potentials (SSEPs) elicited by median nerve stimulation were studied in 17 patients with brain stem tumor. A total of 35 SSEP records were obtained and classified into five groups: 13 in Group I, central conduction time (CCT) < 7.56 msec (within the normal limits); eight in Group II, CCT > or = 7.56 msec; nine in Group III, N20 potential was abolished; four in Group IV, N20 and N18 potentials were abolished; and one in Group V, N20, N18, and P14 potentials were abolished. These SSEP groups were correlated with the size and location of the brain stem tumor on magnetic resonance images. N20 potentials were unchanged in latency in patients with small localized gadolinium (Gd)-enhanced lesions. In contrast, the N20 potentials were abolished in patients with tumors extending to the dorsal pons and the upper medulla oblongata. The extent of nonenhanced low-intensity lesion did not correlate with the changes of the N20 potentials. The degree of the impairment of the N20 potentials reflected the severity of the clinical symptoms. The N20 potential can evaluate brain stem dysfunction caused by brain stem tumor. The N18 potentials were abolished in four patients, in whom the tumor extension (one Gd-enhanced lesion, three low-intensity lesions) involved not only the pons but also the medulla oblongata. Therefore, the N18 potentials are probably generated from the medulla oblongata.

Adolescent↗
PubMed1997

Rotational occlusion of the vertebral artery caused by transverse process hyperrotation and unilateral apophyseal joint subluxation. Case report.

The authors describe transverse process hyperrotation and unilateral apophyseal joint subluxation as a novel mechanism of rotational vertebral artery (VA) occlusion. The patient, a 56-year-old man, complained of episodic bilateral blindness when rotating his head more than 90 degrees to the right. Plain cervical x-ray films showed spondylotic osteophytes of the right C4-5 uncovertebral portion. Dynamic angiography revealed right VA occlusion at C4-5 and left VA occlusion at C1-2 with head rotation to the right. It was demonstrated on three-dimensional images constructed from computerized tomography scans that C-4 transverse process hyperrotation compressed the right VA against the apex of the C-5 subluxating superior articular process via the inner surface of the transverse process anterior root (processus costarius) rather than the osteophytes. It is also proposed that the true site of occlusion is different from that observed in angiographic studies.

Angiography↗
PubMed1997

Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice.

Recently, the sequential changes from adenoma to adenocarcinoma have been well studied in human colorectal carcinogenesis. To study the precise clonal changes from colorectal polyps to cancer, we have established an experimental system to maintain human colorectal polyps in severe combined immunodeficient (SCID) mice that have been improved by the selective inbreeding of C.B17-scid/scid homozygous male and female showing undetectable serum IgG and IgM (< 1 microgram/ml). Two of two solitary polyps from two nonhereditary colon polyp patients, four of five colon polyps from two Peutz-Jeghers' syndrome patients and one polypoid lesion from a familial polyposis coli (FAP) patient grew very slowly but steadily, at approximately one-tenth the rate of their malignant form, (i.e., adenocarcinoma), in the improved SCID mice and were maintained for a long period (more than 2 years), over several mouse generations. However, two polyps from FAP and Peutz-Jeghers' syndrome patients could not be transplanted further because of microinfection at the transplanted site due to incomplete sterilization of original human tumors prior to surgical operation (endoscopic polypectomy). Transplanted colon polyps had a semitransparent, soft and sticky appearance, with cells containing large amounts of mucin. Malignant transformation of human colon polyp to adenocarcinoma has not been observed during the maintenance period (about 2 years) in SCID mice. In the consecutively maintained human colon polyps, however, K-ras mutations were detected at codon 12, while these mutations were not found in their original polyps in the patients.

Adenomatous Polyposis Coli↗
PubMed1997

[Transarterial embolization of a vein of Galen aneurysm: a case report].

This report describes a case of a vein of Galen aneurysm. A 6-month-old baby with a slight head injury was referred to our hospital. CT scans and MR images demonstrated a vein of Galen aneurysm. Left carotid angiogram showed a vein of Galen aneurysm with a large feeding artery from the posterior cerebral artery. Transarterial embolization was performed using Galen coils and Interlocking Detachable Coils. Angiograms after the second embolization revealed complete occlusion of the aneurysm and postoperative course was uneventful.

Cerebral Angiography↗
PubMed1997

[Histological findings in aneurysm treated with IDC: scanning electron microscopical study].

We reported the scanning electron microscopic findings of an aneurysm embolized with interlocking detachable coils (IDC). A 78-year-old man was referred to our hospital because of left hemiparesis and dysphagia. CT scan showed multiple lacunar infarction in the bilateral corona radiata. Angiography demonstrated a small incidental aneurysm of the right internal carotid artery (IC-PC junction). The left hemiparesis gradually improved and 2 weeks after admission the aneurysm was treated with IDC. Three coils were placed in the aneurysm and post-operative angiography demonstrated complete embolization. Dysphagia caused by the pseudobulbar pulse did not improve and, 4 weeks after endovascular surgery, the patient died of aspiration pneumonia. An autopsy was performed and the scanning electron microscopical findings of the aneurysm showed development of endothelial cells on the coil surface. Many clinical reports supported the usefulness of Guglielmi detachable coils (GDC) and several experimental reports demonstrated the intimal proliferation in aneurysms embolized with coils. However, pathological changes of the aneurysms treated with coils have been reported in only four clinical cases. There was no evidence of endothelialization in any of these cases. To our knowledge, our case is the first report describing the endothelial proliferation over the coils. It is necessary to accumulate histopathological data and long-term follow-up in humans treated with coils.

Aged↗
PubMed1997

[Dissecting aneurysm of the middle cerebral artery with subarachnoid hemorrhage and brain infarction: a case report].

This report describes a surgical case of a dissecting aneurysm of the left middle cerebral artery with subarachnoid hemorrhage and ischemic insult. A 48-year-old man with pure motor aphasia was referred to our hospital. CT scans demonstrated subarachnoid hemorrhage in the left frontal region. CT scans on the next day showed a small brain infarction in the left precentral artery and central artery territories. The first left carotid angiograms showed stenosis at the M2 portion of the middle cerebral artery. On the 16th day, the second left carotid angiograms revealed a pearl and string sign. We diagnosed a dissecting aneurysm of the middle cerebral artery. The dissecting aneurysm was wrapped using the pterional approach and STA-MCA anastomosis was also performed. The postoperative course was uneventful and the motor aphasia improved.

Aortic Dissection↗
PubMed1997

Chiral influences of feedback inhibition with dCTP on murine deoxycytidine kinase.

The inhibitory effects of 4 kinds of 2'-deoxy-L-nucleoside 5'-triphosphates, which are enantiomers of natural dNTPs, on murine deoxycytidine kinase (dCK) were investigated. When ATP was used as the phosphate donor, L-dCTP showed significant inhibitory action noncompetitively and competitively with 2'-deoxycytidine (dCyd) and ATP, respectively. Thus L-dCTP, like dCTP, could serve as a feedback inhibitor for dCK. Recently, it has been demonstrated that human dCK can utilize L-dCyd as a substrate (Verri, A. et al. (1997) Mol. Pharmacol., 51, 132). The present results suggest that dCK is also unable to discriminate the chirality of nucleotides at the phosphate donor binding site of the enzyme.

Adenosine Triphosphate↗
PubMed1996

Cloning and sequencing of the cDNA encoding beta-glucosidase 1 from Aspergillus aculeatus.

A cDNA was isolated from an Aspergillus aculeatus cDNA library using synthetic oligodeoxyribonucleotide mixtures that corresponded to the internal amino acid (aa) sequence of mature beta-glucosidase 1 (BGL1). Analysis of the nucleotide sequence of the cloned cDNA insert revealed a 2580-bp open reading frame (ORF) that encoded a 860-aa protein. The deduced aa sequence of the ORF shared sequence similarity with several BGL from other microorganisms.

Amino Acid Sequence↗
PubMed1996

Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice.

In paroxysmal nocturnal hemoglobinuria (PNH), little is known about the molecular events leading to the clinical manifestations except for the hemolysis. To unfold the complex pathophysiology, it is necessary to elucidate the nature of the PNH clone. PNH exhibits an acquired stem cell disorder, a clonal expansion of affected cells, concomitant depression of normal hematopoiesis in bone marrow (BM), and, although infrequently, the development of leukemia. The PNH clone is thus expected to exhibit some neoplastic features. We report here that CD34+ hematopoietic progenitor cells of PNH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice. The hematopoiesis persisted for more than 10 months and did not always need human cytokines. In contrast, the hematopoiesis by control grafts obtained from healthy volunteers required an intense cytokine treatment. This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone.

Adult↗