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Biomedical subjects

M Inagaki

Publications and source records attributed to M Inagaki.

At least 361 records · Page 20Linked to original sources
PubMed1987

Comparison of brain imaging and neuropathology in cases of trisomy 18 and 13.

A comparative study of intracranial imaging and brain pathology in cases of trisomy 18 and 13 was performed. Computed tomography (CT) and ultrasonography (US) revealed disproportional dilatation of the lateral ventricles, a wide Sylvian fissure and a large extracerebellar space with a small cerebellum in each case. In addition, it was characteristic that the occipital poles of the cerebrum protruded in the infero-posterior direction in trisomy 18, and the pontine basis was relatively wide in trisomy 13. The brain pathology in trisomy 18 and 13 demonstrated that the large extracerebellar space is due to the cerebellar dysplasia and protruding occipital poles, the wide Sylvian fissures due to the temporal lobes or external capsular dysplasia, and the relatively wide pontine basis due to meningeal glioneuronal heterotopia. Thus, the characteristic intracranial image in trisomy 18 and 13 suggest microdysgenesis of the brain and might be useful for understanding the pathological structure of the central nervous system in these conditions.

Abnormalities, Multiple↗
PubMed1987

Purified rabbit brain protein kinase C relaxes skinned vascular smooth muscle and phosphorylates myosin light chain.

To clarify the role of protein kinase C in the mechanical response, the effects of exogenous protein kinase C and its cofactors were investigated on skinned smooth muscle preparations of the rabbit mesenteric artery. Addition of protein kinase C with 12-O-tetradecanoylphorbol-13-acetate (TPA) and phosphatidylserine (PS) caused slow inactivation of a maximal Ca2+ contraction of the muscle fiber and correspondingly increased protein kinase C phosphorylation of myosin light chain. Neither protein kinase C nor enzyme cofactors (PS and TPA) produced relaxation of this tissue and all three components caused significant relaxation. Furthermore, when the muscle fiber was activated by Ca2+-insensitive fragment of MLC-kinase, addition of protein kinase C with PS and TPA decreased the tension and increased protein kinase C phosphorylation of myosin light chain. This evidence suggests that protein kinase C phosphorylation of myosin light chain may play an inhibitory role in the contraction of vascular smooth muscle.

Animals↗
PubMed1987

The effects of cycle length on the fragmented atrial activity zone in patients with sick sinus syndrome.

To determine whether atrial pacing effectively decreases the fragmented atrial activity zone (FAZ) in patients with sick sinus syndrome (SSS), we compared FAZ at atrial pacing cycle lengths of 1000-1500 msec (CL1) with that of 750 msec (CL2) in 19 patients with SSS. The FAZ decreased in all patients except two when CL was reduced from CL1 to CL2. The mean decrease was 61.1 msec and was significant (P less than 0.001). Seven patients had frequent episodes of paroxysmal atrial fibrillation or flutter (AFF) prior to atrial pacemaker implantation. Chronic atrial pacing effectively prevented paroxysmal AFF in five of them. We concluded that the normalization of the slow atrial rate decreased FAZ in patients with SSS and may be helpful in preventing atrial tachyarrhythmia in some patients with SSS.

Adult↗
PubMed1987

Functional and morphometrical maturation of the brainstem auditory pathway.

The correlation between the functional and morphological maturation of the auditory pathway was studied in preterm and term infants, children and adults. As to the auditory brainstem response (ABR), peak latencies and I-V interpeak latencies (central transmission) gradually decreased during the third trimester and the first 2 years postnatally. The calculated pontine auditory conduction velocity (PACV) showed dramatic development, which may indicate a more precise auditory function. The PACV value at the age of 2-4 years was almost the same as that of adults. In a histomorphometrical study, the density of nerve cells in the cochlear nucleus and the inferior colliculus was found to decrease with age, that in the inferior colliculus decreasing more slowly. Myelination in the lateral lemniscus proceeded from the late fetal to the infantile period, and the myelin sheaths of large diameter increased mainly in the infantile period. Thus, on studying ABR in combination with the quantitative histomorphometrical investigation, the development of PACV was found to be related to the maturation of nerve cells in the upper nuclei corresponding to each latency as well as myelination of small and large fibers in the auditory pathway. PACV, which can be calculated by studying ABR and magnetic resonance imaging, may be used to assess more accurately the brainstem function in individual patients.

Adolescent↗
PubMed1987

Selective modulation of calcium-dependent myosin phosphorylation by novel protein kinase inhibitors, isoquinolinesulfonamide derivatives.

Ca2+-dependent myosin phosphorylation by Ca2+/calmodulin-dependent myosin light chain kinase (MLC-kinase) and protein kinase C were studied using selective inhibitors, isoquinolinesulfonamide derivatives. Both protein kinases were potently inhibited by 1-(8-chloro-5-isoquinolinesulfonyl)piperazine (HA-156) and its derivatives. Kinetic analysis indicated that HA-156 inhibited both enzymes competitively with respect to ATP, and Ki values of HA-156 for MLC-kinase and protein kinase C were 7.3 and 7.2 microM, respectively. To clarify molecular mechanisms of the isoquinolinesulfonamides to inhibit the Ca2+-dependent protein kinases, we examined the structure-activity relationships of HA-156 and its derivatives. The dechlorinated analogues, HA-100 and HA-142, markedly decreased the affinity for MLC-kinase, suggesting that the inhibitory effect of isoquinolinesulfonamide derivatives depends upon hydrophobicity of the compounds. There is a good correlation between MLC-kinase inhibition and hydrophobicity determined by reverse phase chromatography. In contrast, HA-140 and HA-142 showed weak inhibition of protein kinase C, suggesting that the electron density of the nitrogen in the isoquinoline ring of the compounds correlates with the potency to inhibit protein kinase C activity. These pairs of isoquinolinesulfonamides will aid in elucidating the biological roles of Ca2+-dependent myosin phosphorylation in intact cells. HA-156 and HA-140 inhibited myosin light chain phosphorylation in platelets exposed to collagen, whereas HA-142 and HA-100 did not, significantly. These isoquinolinesulfonamide derivatives should prove to be useful tools for distinguishing between the biological functions of Ca2+-activated, phospholipid-dependent, and Ca2+/calmodulin-dependent myosin light chain phosphorylation, in vivo.

Adenosine Triphosphatases↗
PubMed1987

Isolation of human immunodeficiency virus from a Japanese hemophilia B patient with AIDS.

Human immunodeficiency virus (HIV) was isolated from a Japanese hemophilia B patient with AIDS. This isolate, HIV[GUN-1], was infectious to several mature T-cell lines. Proteins with apparent molecular weights of 160, 55 and 25 kilodaltons were detected. Restriction enzyme cleavage patterns of the proviral genome indicated that HIV[GUN-1] is related to but clearly different from HTLV-III or ARV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1987

[Cisplatin, adriamycin and cyclophosphamide combination chemotherapy of epithelial ovarian cancer].

The chemotherapeutic effects of cisplatin + adriamycin + cyclophosphamide (PAC) on 50 epithelial ovarian cancers were compared with the effects of 5-fluorouracil + cyclophosphamide + mitomycin C (FAM) in 17 patients. The cumulative survival at 5 years was 61.1% in all patients, 62.5% in patients treated with PAC and 54.7% in patients treated with FAM. The 5-year survival rate was 100% in Stage I, 63.5% in Stage II, 40.1% in Stage III and 22.2% in Stage IV. Of 22 patients with Stage III and IV treated with PAC, 16 patients responded (8CRs + 8PRs). The median survival duration of the treated patients was 19 months. On the other hand, of 8 patients treated with FAM, only one patient responded (PR). The median survival duration was 7 months. These results indicated the effectiveness of PAC chemotherapy against advanced ovarian cancer. No severe toxicity was observed during treatment with PAC or FAM.

Adolescent↗
PubMed1987

[Assessment of the establishing individual protocol for effective chemotherapy of ovarian cancer--fundamental research using human tumor-nude mouse system].

Experimental chemotherapy was performed using the human tumor-nude mouse system. The tumors were mucinous cystadenocarcinoma (OVA-1), undifferentiated carcinoma (OVA-2), endometrioid adenocarcinoma (OVA-3), serous cystadenocarcinoma (OVA-4) and three yolk sac tumors (YST-1, -2, -3). The drugs tested were adriamycin, bleomycin, cisplatin, cyclophosphamide, 5-fluorouracil, ifosfamide, mitomycin C, vinblastine, etoposide and teniposide. The dosages employed here were about one-third and one-ninth of the LD50 used for conventional mice. The results obtained were as follows: 1 A clear correlation between the antitumor activity of the drug and the histological type of the tumor was observed. The results indicated the importance of making a chemotherapeutic protocol according to the histological type of the individual tumor. 2 The antitumor activity depended on the dosage of the drug. The results suggested that it was necessary to increase the dosage of the anticancer drugs to obtain further clinical effects on patients with ovarian cancer. 3 The administration of a single drug in a sufficient dosage produced more effective antitumor activity rather than multidrug treatment. The results suggested that combination chemotherapy might not necessarily be the best way to effectively treat patients with ovarian cancer.

Adenocarcinoma↗
PubMed1987

[Antitumor activity of platinum analogs against human ovarian tumors heterotransplanted into nude mice].

The chemotherapeutic effects of CDDP, CBDCA and CHIP on human ovarian cancers heterotransplanted into nude mice (mucinous cystadenocarcinoma OVA-1, poorly differentiated adenocarcinoma OVA-2, endometrioid adenocarcinoma OVA-3, serous cystadenocarcinoma OVA-4, and three yolk sac tumors YST-1, YST-2, YST-3) were examined. OVA-1 did not respond to CDDP, although it responded well to CBDCA and CHIP. OVA-2 responded well to all these platinum analogs. OVA-3 responded well to CDDP, but did not respond to CBDCA or CHIP. OVA-4 responded well to CDDP and CBDCA, but did not respond to CHIP. Tumors YST-2 and YST-3 exhibited broadly comparable sensitivity to CDDP and the two other analogs, and YST-1 was substantially more sensitive to CDDP than to CBDCA or CHIP. The results indicated the necessity of selection of platinum analogs according to the histological types of tumor for the effective treatment of ovarian cancer.

Animals↗
PubMed1987

Specific binding of a novel compound, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) to the active site of cAMP-dependent protein kinase.

The interaction of the catalytic subunit of bovine cardiac muscle cAMP-dependent protein kinase with N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8), the most potent and selective inhibitor toward cyclic nucleotide-dependent protein kinases in the series of isoquinolinesulfonamide derivatives, was studied. The addition of H-8 protected the catalytic subunit of the enzyme in a dose-dependent manner from irreversible inactivation by the ATP analogue p-fluorosulfonylbenzoyl-5'-adenosine (FSBA). The inactivation followed pseudo-first order kinetics and H-8 reduced the steady state constant of inactivation (Ki) without any effect on the first order rate constant (K3). The quantitative binding of H-8 to the enzyme was measured under conditions of thermodynamic equilibrium using a gel filtration method. The catalytic subunit bound approximately 1 mol of drug/mol of protein with apparent half-maximal binding at 1.0 microM drug, whereas the enzyme irreversibly modified by FSBA did not bind the drug, confirming that the enzyme has no site for H-8 in the catalytic subunit other than the active site. The binding studies also showed that H-8 does not require divalent cations such as Mg2+ to bind to the catalytic subunit of the protein kinase. The binding of H-8 to the active site was characterized using FSBA and other affinity labeling reagents which have been postulated to modify residues at or near the active site of the catalytic subunit. H-8 protected the enzyme against inactivation by FSBA and Cibacron Blue F3GA but did not afford any protection against the covalent modification of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and 7-chloro-4-nitro-2,1,3-benzoxadiazole (NBD-Cl), suggesting that the binding site of H-8 does not involve the gamma-subsite of the ATP binding site in the catalytic subunit, since DTNB and NBD-Cl are thought to modify the residues complementary to gamma-phosphate of the ATP molecules.

4-Chloro-7-nitrobenzofurazan↗
PubMed1987

[Antitumor effects of high-dose cisplatin in hypertonic saline against human ovarian tumors heterotransplanted in nude mice].

To overcome the dose limiting toxicity of cisplatin we administered high-dose (12 mg/kg) cisplatin together with hypertonic (3%) saline to tumor-bearing nude mice three times at four day intervals. The heterotransplanted human ovarian tumors consisted of a mucinous cystadenocarcinoma (designated as OVA-1), a poorly differentiated adenocarcinoma (OVA-2), an endometrioid adenocarcinoma (OVA-3) and three yolk sac tumors (YST-1,-2,-3). The mean volumes of the tumors in animals treated with a standard dose 6 mg/kg of cisplatin in 0.9% NaCl or 12 mg/kg of cisplatin in 3% NaCl were, as a percentage of the mean tumor volume in untreated animals: 51 and 26 for OVA-1, 28 and 15 for OVA-2, 11 and 7 for OVA-3, 7 and 14 for YST-1, 3 and 12 for YST-2, and 11 and 10 for YST-3, respectively. The most interesting result was that a high dose (12 mg/kg) of cisplatin succeeded in producing a strong antitumor effect on mucinous cystadenocarcinoma (OVA-1), which was resistant to standard dose cisplatin (6 mg/kg). A comparison of the body weight of tumor-bearing nude mice before and on Day 30 of treatment did not show any appreciable treatment-related changes.

Adenocarcinoma↗
PubMed1987

[Effect of post operative maintenance chemotherapy against ovarian cancer].

The significance of maintenance chemotherapy after surgery for ovarian cancer was examined using a human tumor-nude mouse system. Experiment 1: The human yolk sac tumor of the ovary (YST-2) heterotransplanted into nude mice was used. The tumor-bearing mice were administered 100 mg/kg of 1-Hexylcarbamoyl-5-fluorouracil (HCFU) orally for 60 days after tumor resection. Control mice were given 0.1 ml 0.3% methylcellulose after tumor resection. When the tumor was completely resected by surgery, HCFU treatment succeeded in decreasing the recurrence rate of the tumor, and in improving the survival rate of the host mice. However, when the macroscopic tumor was left in the host mouse, HCFU treatment did not affect either the recurrence rate of the tumor or the survival rate. Experiment 2: The human poorly differentiated adenocarcinoma of the ovary (OVA-2) heterotransplanted into nude mice was used. Administration of 100 mg/kg of HCFU immediately after the heterotransplantation into nude mice for 60 days suppressed the tumor growth. HCFU treatment improved the survival rate of the tumor-bearing mice. The antitumor effect of HCFU on the OVA-2 tumor was confirmed by histological examination. These experiments revealed that the maintenance chemotherapy after surgery for ovarian cancer was important in the effective treatment of the patient (tumor-bearing host).

Animals↗
PubMed1987

[Ifosfamide, cisplatin, adriamycin combination chemotherapy in gynecologic cancer].

Thirteen patients with gynecologic cancer were treated with ifosfamide (2 g X 5), cisplatin (70 mg/m2) and adriamycin (20 mg/m2) combination chemotherapy. The response rate of 7 evaluable patients was 43%, with a median duration of survival of 14 months. Six patients with non-measurable disease are currently free from disease with a median duration of survival of 18 months. This combination caused reversible myelosuppression. No hemorrhagic cystitis was observed.

Adult↗