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Biomedical subjects

T Kagawa

Publications and source records attributed to T Kagawa.

At least 55 records · Page 3Linked to original sources

Localization of mRNA for UDP-galactose: ceramide galactosyltransferase in the brain during mouse development.

UDP-galactose:ceramide galactosyltransferase (CGT) is considered to be a key enzyme in the biosynthesis of galactocerebroside (GalC), a frequently used marker for oligodendrocytes. CGT gene expression has been shown to be restricted to the oligodendrocyte lineage in young adult rat brain. We detected expression of the CGT gene in embryonic mouse brain and spinal cord from E17 onward using an in situ hybridization technique. Localization of CGT messages was restricted to two longitudinal columns of cells in the basal half of the ventricular zone around the fourth ventricule at the most caudal level of the medulla oblongata. After birth, they were distributed in caudal-to-rostral and ventral-to-dorsal gradients. This study shows that CGT mRNA is a good marker for localizing oligodendrocytes, and appears just before the GalC-positive stage.

Aging↗

Inhibitory effect of EGTA on serotonin transport into rabbit blood platelets: possible involvement of the glycoprotein IIb/IIIa complex.

We reported previously that serotonin (5-HT) transport was attenuated by treatment of platelets with EGTA, and that this inhibitory effect of EGTA was restored by CaCl2. In the present study, the inhibitory effect of EGTA was found to be uncompetitive, and no inhibitory effect was observed when EGTA was added at 20 degrees C. Genistein and thyrphostin A47, both protein tyrosine kinase inhibitors, inhibited Ca(2+)-induced restoration of 5-HT transport. In contrast, the protein tyrosine phosphatase inhibitor phenylarsine oxide significantly augmented Ca(2+)-induced restoration of 5-HT transport. These results might support the hypothesis that the glycoprotein (GP) IIb/IIIa complex, a platelet membrane integrin protein, might regulate 5-HT transport into blood platelets. It is conceivable that Ca2+ chelation by EGTA might cause temperature-dependent dissociation of the GP IIb/IIIa complex, which results in the reduction of 5-HT transport. Rearrangement of the GP IIb/IIIa complex by replenishment of the Ca2+ binding sites might restore the EGTA-induced reduction of 5-HT transport.

Animals↗

[Cesarean section in a patient with uncontrolled hyperthyroidism, preeclampsia, and congestive heart failure].

A case of a pregnant woman who underwent urgent cesarean section is presented. The patient had severe hyperthyroidism, preeclampsia, and congestive heart failure, which had not been treated until 36 weeks of gestational age. At 38 weeks, fetal distress occurred and an urgent cesarean section was performed successfully under epidural anesthesia with preoperative treatments using iodide, hydrocortisone and propylthiouracil. The patient required postoperative intensive care for heart failure. Thyroid function of the neonate was almost normal. No abnormality was observed except low birth weight.

Adult↗

[Therapeutic effectiveness of combined microsurgery and radiosurgery in a patient with a huge trigeminal neurinoma].

A case of right trigeminal neurinoma extending from the cavernous sinus to the cerebellopontine angle in a 48-year-old male is reported. The patient first noticed right facial numbness in June 1993. Six months later, he experienced headaches with occasional nausea, diplopia, ataxic gait, tinnitus and dysphagia and was referred to our department on January 21, 1994. Neurological examination on admission showed multiple cranial nerve palsy from the 4th to 11th nerve on the right, and the cerebellar sign on the right. Initial CT and MRI revealed a large mass lesion extending from the right cavernous sinus to the right cerebellopontine angle. On February 16, 1994, radical resection of the tumor, except the lesion invading the cavernous sinus, was performed via a combined retroauricular and preauricular transpetrosal transtentorial approach. The histological diagnosis was neurinoma. The patient's postoperative course was uneventful and there was good clinical improvement, although the right facial numbness and mild diplopia persisted. On April 6, 1994, radiosurgery was performed with a maximum dose of 28 Gy and a marginal dose to 14 Gy to the remaining cavernous sinus lesion. Two weeks after radiosurgery, the patient achieved a complete return to his daily routine. Two-year follow-up CT and MRI showed a small residual les on in the right cavernous sinus alone. There was no evidence of tumor growth. No new neurological deficits had developed, and the patient's the double vision had resolved. Thus, the patient has been able to maintain a satisfactory level of activities of daily living. We wound like to emphasize the clinical value of the strategy used to treat this patient which combined microsurgery with subsequent radiosurgery.

Cranial Nerve Neoplasms↗

Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy.

Using magnetic resonance (MR) diffusion-weighted method, we examined the optic and the trigeminal nerves of jimpy and twitcher mice, considered to be animal models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe disease, demyelination disorder, respectively. In jimpy mice, diffusional anisotropy of optic nerve did not show a significant difference compared to age-matched control mice, suggesting that diffusional anisotropy does exist in absence of multiple layers of myelin sheath. In twitcher mice, diffusional anisotropy was attenuated remarkably in the optic and trigeminal nerves. Loss of axonal straightness on longitudinal section confirmed by electron microscopy appeared to be the principal explanation for it. It is further suggested that this MR diffusion-weighted imaging method enables us to differentiate hypomyelination from demyelination in vivo.

Animals↗

Antibody-dependent cell-mediated cytotoxicity against cell lines generated by liver-specific idiotype-bearing antibody.

We produced a murine monoclonal antibody (mAb), designated H2-mAb, against a fractionated soluble phase of human liver homogenate which antibody reacted with human liver cells. A human antibody possessing the same idiotype as the H2-mAb, designated LSIA (liver-specific idiotype-bearing antibody), can be measured by a sandwich enzyme-linked immunosorbent assay, using the anti-H2 idiotype antibody. The serum level of LSIA in patients with histologically proven chronic hepatitis (CH) was significantly higher than that in healthy subjects and it was also higher than that in subjects with other diseases, including systemic lupus erythematosus. In a comparison between patients with CH type B and those with CH type C, there was no significant difference in serum levels of LSIA. It was possible to purify LSIA from the sera of patients with CH. The purified LSIA bound to the human cell lines Chang and HCC-M, derived from liver cells and a hepatoma respectively, but not to HeLa cells, a uterine carcinoma derivative. The reactivity of this mAb to HCC-M was weaker than that to Change. Moreover, the presence of LSIA caused an antibody-dependent cell-mediated cytotoxic challenge against Change cells in vitro.

Adult↗

Expression of proteolipid protein gene is directly associated with secretion of a factor influencing oligodendrocyte development.

Oligodendroglial cell death in the myelin proteolipid protein (PLP) mutants can be partially rescued by the environment factor(s) supplied by the wild-type cells in vivo and in vitro. It is possible that the presence of PLP or DM-20 results in secretion of a factor or factors in the CNS influencing oligodendrocyte development. We previously showed that DM-20 mRNA is produced in G26 mouse oligodendroglioma, B104 rat neuroblastoma, and B16 mouse melanoma but not in NIH3T3 mouse fibroblast cell lines. Culture supernatants from these cell lines were added to primary glial cell cultures from embryonic day 17 mouse brain. After 4 days, the number of oligodendrocytes present in cultures with supernatants from DM-20-producing cells (G26, B104, and B16) was significantly higher than that of control cultures but not with the NIH3T3 supernatant. To investigate more directly whether the PLP gene expression is involved in this process, NIH3T3 cells (nonneural cells) were forced to produce PLP or DM-20. By addition of the supernatants from the PLP/DM-20 transformants, the number of oligodendrocytes in the mixed glial cell cultures increased. This clearly demonstrates that the expression of the PLP gene is sufficient for and directly associated with secretion of a factor, which influences the oligodendrocyte development.

3T3 Cells↗

Transgenic systems in studying myelin gene expression.

The myelin sheath is produced by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It is necessary to introduce DNA into these cells to study gene regulation and the functions of myelin proteins. Since these cells are labile to commonly used techniques to introduce DNA, a transgenic system must be used for these studies. Myelin basic protein (MBP) and myelin proteolipid protein (PLP) are both highly abundant in CNS myelin, but are also produced in Schwann cells. Various lengths (6.5 kb to 256 bp) of the promoter region of the (classic) MBP gene directed oligodendrocyte-specific expression of the reporter gene in transgenic mice, but no expression was seen in Schwann cells. Promoter regions of the PLP gene (4.2-2.4 kb) seem to contain all the information required for correct spatiotemporal expression, but the level of expression was low. The first intron of the PLP gene is a candidate for the location of the enhancer-like element. Studies on MBP mutant mice carrying wild-type MBP gene or cDNA clearly demonstrated that one function of MBP is to make myelin lamellae compact by fusing the cytoplasmic surfaces of oligodendrocytes into the form of major dense lines. However, functional analysis of PLP gene products using a similar strategy produced confusing results. The wild-type PLP gene introduced into jimpy mutant mice (one of the PLP mutants) did not complement the mutant phenotype. Moreover, overexpression of the PLP gene itself (in wild-type background) was shown to produce a phenotype similar to that of the mutants, including arrest in oligodendrocyte maturation and hypomyelination. Thus, PLP gene products play a fundamental role in oligodendrocyte maturation as well as in the stabilization of myelin structure, and its expression must be tightly regulated.

Animals↗

[Intratumoral pharmacokinetics following intraarterial administration of MCNU in patients with malignant gliomas].

This clinical study was undertaken to examine intratumoral (i.t.) pharmacokinetics after intraarterial (i.a.) administration of MCNU (80mg/m2) in 5 patients with glioblastoma (GB) and 2 with anaplastic astrocytoma (AA). After resection or stereotactic biopsy of the cystic lesion, an Ommaya reservoir was placed into the tumor cavity in all patients. The distribution of MCNU in blood was compatible with a two-compartment model, and the half life of the alpha-phase and beta-phase was 4.1 minutes and 160.4 minutes, respectively. MCNU was detected in the i.t. fluid in 5 cases, 4 of GB and 1 of AA. The concentration of i.t. MCNU gradually increased during the 5 to 30 minutes after i.a. injection to a level about 20.0% of its blood concentration. However, no MCNU was detected in patients showing partial response (3 of GB and 1 of AA) or no change (1 of GB) after the i.a. infusion of MCNU during maintenance chemotherapy. These results suggests that MCNU may transfer into the tumor tissues. Further investigation is warranted.

Adolescent↗

[The efficacy of granisetron as a prophylactic anti-emetic agent used in conjunction with MCNU and VP16 chemotherapeutic regimens in the management of a pediatric case of hypothalamic anaplastic astrocytoma].

The management of a 12-year-old boy with hypothalamic anaplastic astrocytoma is reported herein. The pediatric patient underwent a subtotal removal of his brain tumor, and subsequently received multimodal treatment comprising radiotherapy (30.6 Gy to the whole brain and 50.4 Gy to the local lesion) and immunochemotherapy with MCNU (80 mg/m2, day 1), VP 16 (50 mg/day, days 2 to 6), and interferon-beta (3 x 10(6) units/day, initiating on day 2 for 4 weeks). The immunochemotherapy was given as of 4 weeks after radiotherapy. The administration of anti-cancer drugs caused severe nausea and vomiting, the intra-carotid infusion of MCNU being particularly emetogenic. The multi-modal treatment was then discontinued for a few weeks. A partial response was obtained, and the patient subsequently received 3 courses of maintenance therapy at six-month intervals using the same protocol as for the initial immunochemotherapy. During maintenance therapy, granisetron (40 micrograms/kg) was given intravenously 30 minutes before and one day after the injection of MCNU. Owing to the anti-emetic management of this patient, there were no complications throughout the chemotherapy. The patient has now survived for more than 3 years with a good quality of life, showing a Karnofsky performance score of 90.

Antineoplastic Combined Chemotherapy Protocols↗

[A case report of closing aortic dissection with cardiac tamponade which developed re-dissection three weeks later].

A 57-year-old female with hypotension and consciousness disturbance was referred to our institute. Echocardiography and plain CT revealed cardiac tamponade, but no apparent evidence of aortic dissection was obtained. With sudden onset of hypotension, she was immediately operated without information of aortography, enhanced CT, and MRI. Approximately 200 g of pericardial hemorrhage and slight subadventitial hematoma was grossly found and surface ultrasonography revealed the mild localized intramural hematoma (crescent-shaped translucent layer of at most 5 mm in width) at the proximal ascending aorta. Because neither false lumen with blood flow nor intimal flap was found, pericardial drainage without aortic replacement was performed. However, DeBakey type II of aortic dissection with wide false lumen was found with CT and MRI within three weeks, and re-operation was carried out. The dissection ranged from the ostium of right coronary artery to the beginning of innominate artery, but did not involve the coronary arteries and major branches of aortic arch. The surface ultrasonography and transesophageal echocardiography, as well as preoperative CT and MRI, demonstrated that false lumen was thrombosed except at the anterior aspect of mid-portion of ascending aorta. The ascending aorta was replaced. A careful follow-up is mandatory for even a localized intramural hematoma, which can progress into aortic dissection in a short period.

Aortic Dissection↗

[Pharmacokinetics of intratumoral interferon-gamma activity following subcutaneous administration of recombinant interferon-gamma in a patient with metastatic brain tumor derived from renal cancer].

Pharmacokinetic studies of intratumoral interferon (IFN)-gamma activity were performed 1 week and 1 month after subcutaneous (s.c.) administration of recombinant IFN-gamma (specific activity = 1 x 10(7) units/mg protein) to a patient with metastatic brain tumor in the right occipital lobe derived from primary renal cancer. The patient, a 54-year-old man, underwent total removal of the lesion on April 10, 1991, with placement of an indwelling Ommaya Reservoir in the tumor cavity. The histological diagnosis was clear-cell carcinoma. His postoperative course was uneventful. Due to detection of a new ring-like enhancing mass in the right temporal lobe on serial CT examination on May 27, radiotherapy was discontinued immediately after delivery of a total dose of 30 Gy. Recombinant IFN-gamma was then administered s.c. at a dose of 3 x 10(6) units/day for 6 weeks, and induced a partial response. During IFN-gamma therapy, IFN-gamma activity in intratumoral fluid was measured 0 min, 30 min, 90 min and 6 hours after s.c. injection of IFN-gamma. The level of IFN activity was determined by an enzyme-linked immunosorbent assay. Intra-tumoral IFN-gamma activity gradually increased, and showed the highest of measured values at 6 hours after administration, while serum IFN activity decreased rapidly with a half-life of 30 min. The patient was discharged on July 30, but died from complications of aspiration pneumonia on September 2, 1991.

Adenocarcinoma, Clear Cell↗

Hepatic tumors induced by carbon tetrachloride in transgenic mice carrying a human c-H-ras proto-oncogene without mutations.

Hepatic tumors were generated in mice by repeated administration of carbon tetrachloride (CCl4). Eight transgenic (Tg) mice carrying a human c-H-ras proto-oncogene (rasH2 line) and 9 non-Tg mice were killed at 20 weeks. Tg mice developed more tumors than did non-Tg littermates. Most tumors were neoplastic nodules, but 1 hepatocellular carcinoma (HCC) was found in a Tg mouse at 20 weeks. Three Tg and 2 non-Tg mice were kept without further administration of CCl4. Two Tg mice died at 30 weeks of HCC with intra-abdominal bleeding, and 1 Tg mouse developed HCC with a mesenteric metastasis at 32 weeks. No HCC was found in 2 non-Tg mice at 32 weeks. Although mutations at codon 12, 13, and 61 of the H-ras gene are often found in murine hepatocarcinogenesis, neither the tumors, including one HCC, nor the normal cells revealed any such mutations. These results showed that the unmutated human c-H-ras gene facilitates malignant transformation of hepatocytes when continuous liver-cell death and regeneration is caused by repeated administration of CCl4.

Animals↗

Changes of antigen expression on human hepatoma cell lines caused by sodium butyrate, a differentiation inducer.

We have previously reported the effect of a differentiation inducer, sodium butyrate (SB), on human hepatocellular carcinoma (HCC) cell lines, demonstrating that it was a potent inducer of differentiation. In the present study, we investigated the alteration in expression of an antigen defined by a murine monoclonal antibody, H2, as well as alterations in the expression of other antigens, on the HCC cell lines HCC-T, HCC-M, and PLC/PRF/5, since it is known that specific antigenic changes occur during the differentiation of leukemic cells. The expression of the antigen defined by H2 increased immunocytochemically on HCC-T, HCC-M, and PLC/PRF/5 during treatment with SB. A flowcytometric study showed that almost all the HCC-T and HCC-M cells treated with SB highly expressed this antigen after 5 days' treatment. The antigen expression detected by H2 decreased after the removal of SB from the medium. On the other hand, antigen expression detected by another monoclonal antibody, 5C11, was not changed by this treatment. The expression of intracellular adhesion molecule (ICAM)-1 in HCC-T increased slightly, but that of beta 2-microglobulin and HLA-DR did not change. These results demonstrated that some antigen expression was changed by SB treatment and that the antigen defined by H2 seemed to be highly expressed on human HCC cells in the differentiated state.

Antibodies, Monoclonal↗

Fuzzy and conventional control of high-frequency ventilation.

A high-frequency ventilator was developed, consisting of a single-phase induction motor, an unbalanced mass and a mechanical vibration system. Intermittent positive pressure respiration was combined with high-frequency ventilation to measure end-tidal pCO2. Hysteresis was observed between the rotational frequency of the high-frequency ventilator and end-tidal pCO2. A fuzzy proportional plus integral control system, designed on the basis of the static characteristics of the controlled system and a knowledge of respiratory physiology, successfully regulated end-tidal pCO2. The characteristics of gas exchange under high-frequency ventilation was approximated by a first-order linear model. A conventional PI control system, designed on the basis of the approximated model, regulated end-tidal pCO2 with a performance similar to that of the fuzzy PI control system. The design of the fuzzy control system required less knowledge about the controlled system than that of the conventional control system.

Animals↗