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Biomedical subjects

K Takizawa

Publications and source records attributed to K Takizawa.

At least 19 recordsLinked to original sources

Pathfinding analysis in a glia-less gcm mutant in Drosophila.

Many lines of evidence suggest that glial cells function as guide post cells for axonal pathfinding. However, due to the difficulty in completely eliminating glial cells during development, their functions in axonal pathfinding have not been critically evaluated. In Drosophila gcm mutant embryos, glial cells were genetically eliminated providing us with a unique opportunity to investigate glial functions in nervous system formation. We showed that even in the absence of glial cells the initial axonal extension of pioneer neurons was essentially normal. However, at later stages, axon bundle formation and pathfinding were disturbed in the absence of glial cells, and abnormal migration of glial cells led to misrouting of axons. This indicates that glial cells are required for correct pathfinding at later stages. We propose that glial cells function in a stage-specific manner; they are not required for the initial extension of pioneers but essential for the subsequent extension of pioneers and followers as well as axon bundle formation.

Animals↗

Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production.

Prostaglandins (PGs) are known to play important roles in the proliferation of various types of cancer cells. PGs are produced by the action of cyclooxygenase (COX) enzymes, and two forms of COX, COX-1 and COX-2, have been described. Previous studies have demonstrated that overexpression of COX-2 is associated with colon carcinogenesis, tumor invasion and metastatic potential of colon cancer. In this study, the role of COX-2 on proliferation of squamous cell carcinoma cell lines was investigated. NS-398, a selective COX-2 inhibitor, inhibited proliferation of NA cells, a squamous cell caricinoma cell line that constitutively expresses COX-2 mRNA. NS-398 suppressed the spontaneous production of PGE2 by NA cells, and the antiproliferative effect of NS-398 was abolished by addition of PGE2. Similar results were obtained from experiments using COX-2 antisense oligonucleotide. These results suggest that specific inhibition of COX-2 inhibits proliferation of cancer cells expressing COX-2 mRNA via suppression of PGE2 production.

Carcinoma, Squamous Cell↗

[Assessment of intra and extrahepatic perfusion during hepatic artery infusion chemotherapy using slow-injected gadolinium-enhanced MR imaging through implanted catheter-port-system].

Twenty-four studies of intra-arterially slow-injected gadolinium-enhanced MR imaging through an implanted catheter-port system (reservoir-MR) were carried out in 15 patients with liver tumor. The flow rate of gadolinium injection was 0.1 ml/sec and a total of 3 mL was injected. Six consecutive phases, each with an acquisition time of 14 seconds, were obtained every 30 seconds. In all studies, the signal intensity of the drug delivery portion became very high. Twenty-three of 24 studies showed intrahepatic perfusion in the first phase. The hepatic vein was enhanced at the first phase in 10 and the second phase in 14. The abdominal aorta was enhanced at the second phase in all 24 studies. The portal vein was enhanced at the first phase in 4, the second phase in 13, and the third phase in 7 studies. Both intra- and extrahepatic perfusion were more clearly demonstrated by reservoir-MRI than by digital subtraction angiography through an implanted catheter-port system (reservoir-DSA); however, morphological changes in the hepatic artery were better demonstrated by reservoir-DSA than by reservoir-MRI.

Adult↗

[Ultra-slow infusion dynamic MRI using an infusion pump: a new method for the evaluation of drug distribution in arterial infusion chemotherapy].

Ultra slow infusion dynamic MR imaging using an infusion pump(IP-MRI) was performed in six patients with metastatic liver tumor or unresectable gastric cancer to evaluate ant-cancer drug distribution. We used un implanted port for the infusion of Gd-DTPA by infusion pump. On IP-MRI, the speed of Gd-DTPA infusion was very slow (0.01 ml/sec) , the same as drug infusion at chemotherapy. The contrast enhancement of tumors was extremely clear. Therefore, IP-MRI was considered feasible for the evaluation of drug distribution.

Adult↗

[Anesthetic management of a child with Klippel-Feil syndrome associated with severe scoliosis].

We experienced an anesthetic management of a female child with Klippel-Feil syndrome complicated with severe scoliosis. This patient showed airway problems in anesthetic management because of limited neck movement due to fused cervical supine and winding airway due to scoliosis. A laryngeal mask (LM) was useful for ventilation but we fitted LM carefully because of her orolaryngeal anomaly. Intubation was very difficult through LM because the axis of LM was not on the laryngeal axis and the tip of the tracheal tube caught the epiglottis and arytenoid cartilage.

Anesthesia, General↗

Response of the radial artery to three vasodilatory agents.

We examined the response of the radial artery to vasoactive agents (isosorbide dinitrate, ISDN, 1 mg, 3 mg, and 5 mg; verapamil, 1 mg, 3 mg, and 5 mg; and lidocaine, 10 mg, 30 mg, and 50 mg) in 100 consecutive patients admitted for elective coronary angiography. The drug solutions were directly injected into the radial artery from the puncture site. As a result, 5 mg of ISDN increased the diameter of the radial artery by 31% and 28.8% at the proximal and distal sites, respectively. Similarly, 5 mg of verapamil increased it by 9% and 10.8% at the proximal and distal site, respectively. But 10 mg of lidocaine decreased it by -15.6% and -12.1% at the proximal and distal site, respectively. At the doses utilized, ISDN was the most potent vasodilator for the radial artery and lidocaine caused paradoxical vasoconstriction.

Adult↗

Isolation of Candida dubliniensis from the oral cavity of an HIV-positive child in Brazil.

Candida dubliniensis is a newly-recognized Candida species and an important infectious pathogen, particularly for HIV-positive patients. >From oral smear samples from the radix linguae of 173 HIV-positive children, we obtained four yeast isolates which took a blue-green color on CHROMagar Candida plate at 37 degrees C for 48 hours from one HIV-positive 3-year-old boy in Brazil. The isolates were difficult to grow on potato dextrose agar plate at 42 degrees C, produced abundant chlamydospores on a cornmeal agar plate with Tween 80, and sprouted germ tubes in saline with horse serum, and the antigenic profile by CANDIDA CHECK test was useless. Carbohydrate assimilation tests by ID32C showed no reference code number in the reference book. The isolates were subjected to molecular biological assay of the DNA sequence of the large-subunit ribosomal DNA region (D1/D2) and randomly amplified polymorphic DNA (RAPD). The DNA sequence agreed with those of standard C. dubliniensis strains, and therefore, the isolates were identified as C. dubliniensis. RAPD band pattern analysis indicated that the clinical isolates might summarize one genotype. Although the child did not present oral lesions, the fungus might be latent for opportunistic infection.

Brazil↗

[A case of HTLV-1 associated myelopathy (HAM) with pseudopseudohypoparathyroidism].

We report a case of HTLV-1 associated myelopathy (HAM) with pseudopseudohypoparathyroidism (PPHP). A 57-year-old woman, without a history of blood transfusion, was admitted with numbness and pain in her legs. Pain sensation in both legs was reduced and tendon reflexes were exaggerated. She exhibited spastic gait. The diagnosis of HAM was made because of positive antibody for HTLV-1 in blood and CSF. She also had features of Albright syndrome (short stature, round face, and short fourth metatarsals) without abnormal calcium and phosphorus metabolism, leading to the diagnosis of PPHP. Brain CT revealed bilateral calcification of the basal ganglia. Although HAM rarely accompanies pseudohypoparathyroidism (PHP), there are few reported cases of HAM associated with PPHP. The exact mechanism of HAM is not known, but it is thought to involve an immune-related process. Since PHP is considered to induce a state of mild immunosuppression through reduction of 1,25-dihydroxyvitamin D3, it is possible that susceptibility to HAM could be augmented in the presence of PHP. If PPHP should be an incomplete form of PHP, a similar mechanism may be involved in the association of PPHP and HAM.

Female↗

[X-Linked Charcot-Marie-Tooth disease with a new mutation (Thr191Ala) in the connexin32].

We report a 59-year-old man with X-linked Charcot-Marie-Tooth (CMT) disease and a new point mutation in the connexin32 gene. The patient first noticed mild gait disturbance five years previously. On admission, he exhibited muscle atrophy and weakness in the distal part of both legs, mild muscle atrophy of both hands without weakness, and a minimal reduction of touch sensation in the right dorsal foot. Nerve conduction velocity of the peripheral nerves was diffusely reduced. Electromyography exhibited high-amplitude, long-duration, polyphasic motor unit potentials in the muscles of the extremities. Fibrillation potential and positive sharp wave were present in the affected muscles. Cerebrospinal fluid protein was slightly elevated. The polyneuropathy did not respond to high-dose corticosteroid treatment, and showed very slow progression. His parents were not consanguineous. His father and two sons were healthy, but similar illness (more severe) was suspected in his younger brother. Gene analysis (Southern hybridization) did not reveal any duplication or deletion in the CMT 1 A-REP region. However, a novel mutation (Thr191Ala) was detected in the connexin32. Although more than 160 mutations in the connexin 32 gene have been identified worldwide, approximately ten mutations have so far been reported in Japan. In comparison with X-linked CMT patients with other connexin32 mutations, the present case was characterized by late onset and mild neurological manifestation. Gene analysis provides a useful tool for diagnosing cases with slowly progressive, motor dominant polyneuropathy of unknown origin.

Charcot-Marie-Tooth Disease↗

Nitric oxide up-regulates the expression of intercellular adhesion molecule-1 on cancer cells.

Nitric oxide (NO) is an unstable free radical that functions as a cytotoxic agent secreted by macrophages to kill cancer cells. Here we report the effect of NO on the expression of intercellular adhesion molecule-1 (ICAM-1) on cancer cells. NO donors such as SNP, SNAP and SIN-1 up-regulated the expression of ICAM-1 on NA cells, a squamous cell carcinoma cell line. Northern blot analysis showed that the induction of ICAM-1 might be due to transcriptional induction of ICAM-1 mRNA. Up-regulation of ICAM-1 mRNA by NO donors was inhibited by carboxy-PTIO, a NO scavenger. Although NF-kappaB activity was induced by NO donors, AP-1 was not induced by them. Staurosporin, a protein kinase C (PKC) inhibitor, inhibited the induction of ICAM-1 on NA cells by NO, whereas genistein, a protein tyrosine kinase inhibitor, did not. These findings indicate that NO up-regulates ICAM-1 expression on cancer cells by a regulatory mechanism involving PKC and suggest that NF-kappaB, but not AP-1, might be involved in induction of ICAM-1 by NO in cancer cells.

Benzoates↗

Cervical adenocarcinoma, a novel combination chemotherapy with mitomycin C, etoposide, and cisplatin for advanced or recurrent disease.

We review the cases of 31 patients with stage IVb or recurrent cervical adenocarcinoma who were treated with combination chemotherapy utilizing mitomycin C, etoposide, and cisplatin (MEP). The total response rate was 16.1% (95% confidence intervals (CIs), 5. 5 to 33.7%) with 4 patients having a complete response (CR) and 1 having a partial response. In patients with no prior chemotherapy, the response rate was 26.7% (95% CIs, 7.8 to 55.1%) with 2 of these CR patients surviving over 3 years, 1 a disease-free survival. A marked response was found in distant recurrent lesions. The major toxicity was myelosuppression. Forty-five percent of patients had leukocytopenia above grade 3; thrombocytopenia and anemia were not common. In patients with cervical adenocarcinoma and no prior chemotherapy, there was a moderate response to MEP therapy.

Adenocarcinoma↗

Expression of goose parvovirus VP1 capsid protein by a baculovirus expression system and establishment of fluorescent antibody test to diagnose goose parvovirus infection.

The gene encoding VP1 capsid protein of a goose parvovirus was cloned into a baculovirus transfer vector and a recombinant baculovirus was produced. The recombinant virus expressed a protein of 88 kDa corresponding to the molecular weight of VP1 protein and the protein was detected by immunoblotting. By indirect fluorescent antibody (IFA) test, the expressed protein was detected in the nucleus of the insect cells as big granules and electron microscopy also showed several big granules in the nucleus infected with the recombinant virus. The IFA test was developed for screening antibody in Muscovy ducks.

Animals↗

Identification and genetic homogeneity of Trichophyton tonsurans isolated from several regions by random amplified polymorphic DNA.

Trichophyton tonsurans is an anthropophilic dermatophyte mostly causing tinea capitis and tinea corporis. This study was carried out to identify T. tonsurans and to clarify whether it has any genetic differences depending on the phenotype or region of isolation by random amplified polymorphic DNA (RAPD) analysis with three random primers. The assay was performed in 11 Korean, 2 Japanese, 2 Taiwanese, 5 Brazilian and 1 American isolates of T. tonsurans together with the other 10 anamorphic species of dermatophytes and 3 Arthroderma spp. All tested species of dermatophytes showed distinct bands and T. tonsurans was differentiated from other dermatophytes. It was most clearly differentiated from T. mentagrophytes by using primer 5'-GAAGGCTCCC-3' (OPAO-15). No difference was found in RAPD band patterns in all strains of T. tonsurans with these random primers. It was considered that T. tonsurans is a genetically homogeneous species regardless of its isolation regions, morphologic or physiologic characteristics.

DNA, Fungal↗

Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorouracil in a cancer cell line via a NF-kappaB independent pathway.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) are common anti-tumour agents, and the anti-tumour effect of CDDP and 5-FU are synergistically enhanced by combined treatment. To clarify the mechanisms of this synergism, we examined the effect of CDDP and 5-FU on the expression of cell adhesion molecules involved in recognition of cancer cells by T lymphocytes. When NA cells, a squamous cell carcinoma cell line, were exposed to CDDP and 5-FU for 18 h, the expression of intercellular adhesion molecule-1 (ICAM-1) was synergistically induced, whereas CDDP or 5-FU alone did not induce the expression of ICAM-1, as determined by flow cytometry. Expression of ICAM-2 and ICAM-3, which are recognized by the same counter receptor on T-cells, were not up-regulated by CDDP and 5-FU. RT-PCR analysis showed that the induction of ICAM-1 on NA cells might be due to transcriptional induction of ICAM-1 mRNA. Treatment with genistein, a protein tyrosine kinase (PTK) inhibitor, inhibited the induction of ICAM-1 on NA cells by CDDP and 5-FU, whereas staurosporin, a protein kinase C inhibitor, did not. Although CDDP and 5-FU induced binding at the nuclear factor kappa B (NF-kappaB) site in the ICAM-1 promoter, pretreatment with genistein did not prevent CDDP and 5-FU-induced binding at the NF-kappaB site. Moreover, a NF-kappaB nuclear translocation inhibitor did not inhibit the induction of ICAM-1 expression by treatment with CDDP and 5-FU. The synergistic effect of CDDP and 5-FU was not specific to NA cells, since ICAM-1 was synergistically induced by CDDP and 5-FU on HSC-4 cells, a squamous cell carcinoma cell line. These findings indicate that treatment with CDDP and 5-FU induces ICAM-1 expression by a NF-kappaB independent regulatory mechanism involving PTK.

Antigens, CD↗

Altered growth response of oral mucosal keratinocytes in p53-deficient mice.

P53 has important regulatory functions in cell growth, differentiation and apoptosis. Here we analyzed the effects of p53 on the growth response of oral mucosal keratinocytes (OMKCs) using p53-deficient (p53-/-) mice. No morphological difference was found between p53-/- and wild-type (p53+/+) oral mucosa. In a long-term culture, p53-/- OMKCs continued to proliferate past the point at which p53+/+ became senescent. The percentage of p53-/- OMKCs in the G0/G1 phase was lower than that of p53+/+ OMKCs. Proliferation of cultured OMKCs induced by epidermal growth factor (EGF) and interleukin-(IL)-1alpha was more strongly enhanced in p53-/- than in p53+/+ mice. Such an enhanced response was not due to increased mRNA expression of growth factor receptors. These data suggest that p53 acts as a modulator of G1 arrest in OMKCs and is also involved in the regulation of responses to EGF and IL-1alpha without affecting the expression of their receptors.

Animals↗

Tetranorditerpene lactones, potent antifungal antibiotics for human pathogenic yeasts, from a unique species of Oidiodendron.

The culture filtrate of a fungus isolated from decaying Picea glauca wood and tentatively identified as Oidiodendron cf. truncatum showed strong antibiotic activity against the pathogenic yeast, Candida albicans. Four new tetranorditerpenoids, oidiodendrolides A (3), B (4), and C (5) and oidiodendronic acid (7) were isolated along with three known tetranorditerpenoids, LL-Z1271 alpha (= PR1387) (1), PR1388 (2), and acrostalidic acid (6), from rice fermented by the above fungus. The structures of oidiodendrolides A (3), B (4), and C (5) and oidiodendronic acid (7) were established on the basis of spectroscopic and chemical investigations. The antifungal activity of the above tetranorditerpenoids against the pathogenic yeasts, Candida albicans and Cryptococcus neoformans is discussed.

Antifungal Agents↗

Synthesis and biological evaluation of 1,2,3,4-tetrahydroisoquinoline derivatives as potent and selective M2 muscarinic receptor antagonists.

A series of 1,2,3,4-tetrahydroisoquinoline derivatives containing the 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton were prepared and evaluated for their in vitro binding affinities to muscarinic receptors and for antagonism of bradycardia in vivo. Among them, compound 3f had the highest affinity for M2 muscarinic receptors in the heart (pKi = 9.1) with low affinity for M3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the benzene ring fused piperidine and the alkyl linker chain length are crucially important for increased M2 affinity.

Animals↗

[Serial hepatic and splenic volumetry in acute severe hepatitis].

In this study, we elucidate a relationship between final outcome and changes in hepatic and splenic volume in patients with acute severe hepatitis. The subjects were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30 with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver and spleen volume were measured by CT initially on hospitalization and subsequently 1 to 40 days after hospitalization, and the scans were analyzed retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non-survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased, spleen volume increased in none of the survivors, whereas it increased in 11 of the 14 non-survivors. In survivors there was a close parallelism between changing rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001). These observations suggest that the decrease of liver volume accompanied by that of spleen volume implies a good prognosis, while the decrease without such accompaniment implies a bad prognosis.

Acute Disease↗