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Biomedical subjects

M Kasai

Publications and source records attributed to M Kasai.

At least 325 records · Page 18Linked to original sources
PubMed1991

Structure and conformation of a novel inhibitor of angiotensin I converting enzyme--a tripeptide containing phosphonic acid.

A novel phosphotripeptide, (IR)-1-(N-(N-acetyl-L-isoleucyl)-L-tyrosyl)amino-2-(4-hydroxyphenyl)ethy l- phosphonic acid, is a potent inhibitor of angiotensin I converting enzyme (ACE). ACE inhibitory activity in vitro of the peptide is comparable to that of captopril. Its diethylester (C29H42N3O8P, molecular weight, 591.6) crystallizes in the monoclinic space group C2, with cell constants: a = 25.666(9), b = 9.590(8), c = 13.557(2)A, beta = 91.65(2) degrees, Z = 4, Dc = 1.17 g/cm3. The structure was solved by MULTAN 11/82 and refined by full matrix least-squares methods to a final R-factor of 0.063 for 2123 unique reflections (F greater than 3 sigma(F] measured on an Enraf-Nonius CAD-4 diffractometer (CuK alpha, lambda = 1.541 8 A, T = 295 K). The absolute configuration of the alpha-carbon where the phosphonic acid is attached was determined unequivocally by referring to the L-isoleucyl moiety whose absolute configuration is known. The conformation of the molecule is relatively rigid owing to the intramolecular requisites and the resultant relative disposition of hetero atoms, which are necessary to its biological activities, are confined to the corresponding disposition in captopril.

Amino Acid Sequence↗
PubMed1991

The derivation of a novel mitomycin skeleton: 3 alpha-alkoxymitomycin.

The first example of C-3 alkoxylation in mitomycins has been achieved. 3 alpha-iso-Propoxy-10-O-decarbamoylmitomycin D (4) and 3 alpha-iso-propoxymitomycin D (5) were derived from mitomycin D (3) under decarbamoylation conditions with iso-propoxide. Under similar conditions 3 alpha-iso-propoxy-10-O-decarbamoylporfiromycin (8) and 3 alpha-methoxy-10-O-decarbamoylmitomycin B (11) were also derived from porfiromycin (6) and mitomycin B (9), respectively. The mechanism of generation of these novel analogs was based on the premise that the key intermediate of hydroquinone iminium salt (14) was led through the iminium salt (13), followed by alkoxide addition and oxidation.

Mass Spectrometry↗
PubMed1991

The configuration of mitiromycin and its derivation from mitomycin B.

The configuration of mitiromycin (2) was first determined by NMR experiments including the NOE technique. The absolute structure of 2 was related to mitomycin B (3) because 2 was derived from 3 under basic conditions. The ketonic form 4 was presumed to be involved in the generation of 2.

Antibiotics, Antineoplastic↗
PubMed1991

Electrophysiological analysis of structural aspects of voltage-dependent SR K+ channel.

This article presents a brief review on the electrophysiological analysis of the structural aspects of the voltage-dependent SR (sarcoplasmic reticulum) K+ channel. In the first half, early attempts to determine the physical dimensions of the ion conducting mechanism such as the mouth, narrow tunnel, or ion selective filter of the channel, are reviewed. The depicted cartoon of the SR K+ channel, as an extremely short, busy district with a big mouth on each side, is quite similar to the recently-obtained reconstructed structural image of the acetylcholine receptor channel. In the latter half, we introduce our recent attempts to draw a physical image of the gating mechanism of the SR K+ channel. We examined, for example, the location of the gate and the voltage sensor, and the relationship between them. It is suggested that the gate and the sensor are connected tightly and that the sensor would be exposed to the surface of the lumen side of SR when the gate opens. Finally, the issue of substates in SR K+ channel is discussed. It is implied that the substrate-conductances reflect a partial occlusion of the pore by an intermediate-open gate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

[Development of image processing system for fundus video-angiography with non-stroboscopic illumination].

A new recording system for fluorescein video-angiography using a highly sensitive color charge coupled device (CCD) camera was developed. An image processing unit installed in a personal computer made it possible to process video signals from the camera and/or a video tape recorder. Functions of the unit are on-line and/or off-line operations on image data such as smoothing, digital subtraction, differentiation etc. Application of the unit improved the quality of images observed on a monitor screen. This system enabled observation of the ocular fundus with illumination of low intensity, which reduced physical and psychological suffering of patients. In addition continuous and whole sequences of fundus fluorographs were recorded, without using strong stroboscopic lights. Extraction of a clear image from ambiguous records at any moment was possible through off-line processing on the stored data. Furthermore quantification of the blood flow in any blood vessels was possible by subtracting two successive images. With this system, quantitative expression of a slight difference in the color of the fundus could be made through calculation of the ratios among R-, G-, and B-components of signals at any place. Finally, comparative study of images of the fundus with natural color could be made with those of fluorography. These features may provide further information on the physiology and pathology of the fundus.

Animals↗
PubMed1990

Peptide behaviour and analysis on a chemically stable C18-bonded vinyl alcohol copolymer column with alkaline and acidic eluents.

C18-bonded vinyl alcohol copolymer (ODP) gel showed no weight loss or decrease in column efficiency for alkyl alcohols after being immersed in aqueous solutions of pH 2 and 10 at 50 degrees C for 48 h, and only a 1% weight loss and a slight decrease in alkyl alcohol retention volumes after similar immersion at pH 13. The chemical stability of the ODP gel was further demonstrated in analyses of acidic, neutral and basic peptides on an ODP column with eluents of pH 3-10, which showed that the peptides differ considerably in the sensitivity of their retention behaviour to eluent pH, even though hydrophobic interaction invariably appeared to be the main retention mechanism. The ODP column was therefore applied to the analysis and alignment of lysilendopeptidase (LEP) peptides derived from reduced and S-carboxymethylated carboxyl proteinase (Rcm-P-CP) of Pseudomonas sp. 101. One acid-soluble and seven alkaline-soluble LEP peaks were found in analyses on the ODP column using acidic and alkaline eluents, respectively. The chymotryptic peptides of Rcm-P-CP were first separated on an ODS column with an acidic eluent, and the eight eluates which contained lysine residue, as determined by amino acid analysis, were then analysed on the ODP column with an alkaline eluent, resulting in a further separation of each into several peaks and thus in the recovery of fractions of pure peptides. The LEP peptide alignment was then determined by overlapping the sequences of the chymotryptic peptides with the C- and N-terminal regions of the LEP peptides.

Chromatography↗
PubMed1990

Ca2+ pump and Ca2+/H+ antiporter in plasma membrane vesicles isolated by aqueous two-phase partitioning from corn leaves.

Plasma membrane vesicles, which are mostly right side-out, were isolated from corn leaves by aqueous two-phase partitioning method. Characteristics of Ca2+ transport were investigated after preparing inside-out vesicles by Triton X-100 treatment. 45Ca2+ transport was assayed by membrane filtration technique. Results showed that Ca2+ transport into the plasma membrane vesicles was Mg-ATP dependent. The active Ca2+ transport system had a high affinity for Ca2+(Km(Ca2+) = 0.4 microM) and ATP(Km(ATP) = 3.9 microM), and showed pH optimum at 7.5. ATP-dependent Ca2+ uptake in the plasma membrane vesicles was stimulated in the presence of Cl- or NO3-. Quenching of quinacrine fluorescence showed that these anions also induced H+ transport into the vesicles. The Ca2+ uptake stimulated by Cl- was dependent on the activity of H+ transport into the vesicles. However, carbonylcyanide m-chlorophenylhydrazone (CCCP) and VO4(3-) which is known to inhibit the H+ pump associated with the plasma membrane, canceled almost all of the Cl(-)-stimulated Ca2+ uptake. Furthermore, artificially imposed pH gradient (acid inside) caused Ca2+ uptake into the vesicles. These results suggest that the Cl(-)-stimulated Ca2+ uptake is caused by the efflux of H+ from the vesicles by the operation of Ca2+/H+ antiport system in the plasma membrane. In Cl(-)-free medium, H+ transport into the vesicles scarcely occurred and the addition of CCCP caused only a slight inhibition of the active Ca2+ uptake into the vesicles. These results suggest that two Ca2+ transport systems are operating in the plasma membrane from corn leaves, i.e., one is an ATP-dependent active Ca2+ transport system (Ca2+ pump) and the other is a Ca2+/H+ antiport system. Little difference in characteristics of Ca2+ transport was observed between the plasma membranes isolated from etiolated and green corn leaves.

Adenosine Triphosphate↗
PubMed1990

Age-related hyperplasia of the thymus and T-cell system in the Buffalo rat. Immunological and immunohistological studies.

This report describes the development of hyperplasia of both the thymus and the peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats do not show age-related thymic involution, but rather develop thymic hyperplasia with advancing age. This thymic growth is expansile and there is no infiltration of the surrounding tissues. Because the enlarging thymus occupies the thoracic cavity, most of the rats die of respiratory failure by the age of 24 months. Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and the large number of proliferating lymphocytes. The hyperplastic epithelial cells are bizarre in shape and strongly positive when stained with Th-3 monoclonal antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes within the hyperplastic thymus are similar to those seen in young rats of other species. The high level of T-cell emigration from the thymus to the periphery appears to persist throughout life, since the percentage of normal splenic T-cells also increase with advancing age and exceed 70% of the total by 24 months of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial cells can be prevented by hypophysectomy.

Aging↗
PubMed1990

Osmotic responses of rat paraventricular neurons by pressure ejection method.

Extracellular recordings were made from 44 spontaneously active neurosecretory and 43 unidentified neurons in the paraventricular nucleus (PVN) of the hypothalamus in urethane-anesthetized rats. Physiologically hypertonic (+30 mOsm/kg, NaCl or mannitol) and hypotonic (-30 mOsm/kg) solutions were applied by pressure through multibarrel micropipettes to the immediate vicinity of neurons. Of 44 neurosecretory neurons tested, 31 (70%) were unaffected by locally applied osmotic stimulation, and the remaining 13 were excited. Of these 31 osmotically unresponsive neurosecretory neurons, 21 were further tested with very strong hypertonic (+260 mOsm/kg, NaCl) solution, and only 7 were affected. Of 43 unidentified neurons, 28 (65%) were unaffected by osmotic stimulation, and 12 were excited. Accordingly, only parts (30%) of both the neurosecretory and unidentified neurons in the PVN were found to be osmosensitive. We concluded that some neurons in the rat PVN are osmosensitive and osmosensitivity is not specific to neurosecretory neurons in the PVN.

Action Potentials↗
PubMed1990

In vivo administration of cytokine in allogeneic bone marrow chimeras.

When we analyzed the in vivo efficacy of cytokine administration in murine allogeneic bone marrow chimeras, mitogen-induced responses to ConA, PHA, LPS, or PWM were increased by the in vivo administration of human recombinant granulocyte colony-stimulating factor (rG-CSF), human recombinant interleukin 2 (rIL-2), or WEHI-3B conditioned medium (CM). Furthermore, we found increased alloreactive mixed lymphocyte reactions (MLRs) against donor and/or host type alloantigens in spleen cells from (BALB/c----C3H/He) chimeras, although cytotoxic activity against BALB/c or C3H/He target cells was not detected in spleen cells from these chimeras. Since no significant increase of T cells or Ia positive cells was observed, some functional activation, rather than changes in the cell count, appeared to relate to increase immunoreactivity. An increased IL-2 production in spleen cells from chimeras injected with cytokine was observed shortly after the cessation of cytokine administration. Thereafter, an IL-2 production in these chimeras decreased around 45 days after bone marrow transplantation and then recovered nearly to the control level. An increased IL-2 responsiveness was also observed in spleen cells from these chimeras. These findings suggest that the in vivo administration of rG-CSF as well as rIL-2 or WEHI-3B CM (IL-3) can modulate the immunoreactivity in chimeras via the network of immune systems.

Animals↗
PubMed1990

A simple method for mouse embryo cryopreservation in a low toxicity vitrification solution, without appreciable loss of viability.

Mouse morulae were exposed to solutions containing 30-50% of permeable agents (ethylene glycol, glycerol, propylene glycol) in modified phosphate-buffered saline (PB1 medium) at 20 degrees C for 20 min. A high percentage of them developed to expanded blastocysts in culture, after exposure to 30% and 40% ethylene glycol (98 and 84%, respectively), or 30% glycerol (88%). Ethylene glycol and glycerol were diluted to 30 and 40% with PB1 medium or with PB1 containing 30% Ficoll or 30% Ficoll + 0.5 M-sucrose, immersed in liquid nitrogen in straws and warmed in 20 degrees C water. Solutions containing 40% of a permeable agent with Ficoll did not crystallize during cooling or warming. Mouse morulae were exposed to 40% ethylene glycol in PB1 medium containing 30% Ficoll (EF) or PB1 medium + 30% Ficoll + 0.5 M-sucrose (EFS) for 5-20 min at 20 degrees C. EFS solution was non-toxic to the embryos during 5 min of exposure. When embryos, equilibrated in EFS solution for 2 or 5 min at 20 degrees C, were vitrified at -196 degrees C and were warmed rapidly, nearly all embryos developed in culture (97-98%), and 51% developed to live young at term after transfer. This method, which results in virtually no decrease in embryonic viability, may be of practical use for embryo preservation.

Animals↗
PubMed1990

Inhibitory effect of bestatin on the growth of human leukemic cells.

We examined the effect of bestatin (Ubenimex) on the growth of human leukemic cells (i.e, HL-60, K562, MT-1, MT-2, Molt-4, and Raji cells). The growth of each cell line was inhibited by the cocultivation with bestatin at higher concentrations than employed for clinical use in Japan. [3H]TdR incorporation was also inhibited in MT-1 and MT-2 cells by treatment with bestatin. Degenerated cell-to-cell adhesion was observed among the treated cells. These findings suggest that the inhibitory effect on some leukemic cells, especially on MT-1 cells, results from the inhibition of DNA synthesis.

Antibiotics, Antineoplastic↗
PubMed1990

The derivation of 1a-demethylmitomycin G from mitomycin C.

Mitomycin G (2) was derived from porfiromycin (10b) in 3 steps via the methanesulfonate (14b) in an overall yield of 39%. On the basis of the established method for the introduction of an exomethylene group in mitomycins with a 9a-methoxy group, the preparation of biologically more important 1a-demethylmitomycin G (5) from mitomycin C (1) was accomplished by the use of a protective acetyl group on the aziridine in an overall yield of 57%. 1a-Demethylmitomycin K (6) was obtained from 5 in a yield of 42%. In a preliminary evaluation of their antitumor activity, compound 5 showed superior activity against sarcoma 180 (sc-ip) to its 1a-methyl congener, i.e., mitomycin G (2).

Animals↗
PubMed1990

Method for the quantitative evaluation of the distribution pattern of nuclei in normal and malignant endometrial epithelia.

A quantitative method of evaluating the pattern of distribution of nuclei within a cell cluster was developed and applied to endometrial cytology. The distribution pattern (DP) is mathematically expressed using a "DP index," which can be determined as a product of the square root of the nuclear density, square root of n0, and the mean distance between the two nearest nuclei, r. The DP index has a limited range of decreasing values from 1.074 to 0.5 to 0, indicative of regular, random and aggregated patterns of nuclear distribution, respectively. The estimated DP index was 0.831 +/- 0.031 (mean +/- standard deviation) in the clusters of normal endometrial epithelial cells from 16 nonneoplastic cases, but 0.638 +/- 0.041 in malignant epithelia from 19 cases of well-differentiated adenocarcinoma. The index of normal epithelia was close to 0.877 of the regular hexagonal distribution pattern. Contrary to this, the DP index was significantly smaller in well-differentiated adenocarcinoma (P less than .001), approaching 0.5, the theoretical value of a random distribution pattern. These findings suggest that quantitative analysis of the distribution pattern of nuclei can be a useful aid in the cytodiagnosis of endometrial lesions.

Adenocarcinoma↗
PubMed1990

[Clinical application of magnetic resonance imaging (MRI) in uterine disease].

We investigated the value of MRI in investigating uterine anatomy and disease. 1. Normal uterus: The signal intensity and endometrial thickness changed during the menstrual cycle. Endometrial thickness in the secretory phase was 12.8 +/- 3.6 mm, significantly greater than in the proliferative phase (5.4 +/- 0.7 mm, p less than 0.01). In contrast, endometrial thickness was reduced in postmenopausal women (4.1 +/- 0.9 mm) and was never over 6 mm. 2. Uterine disease: a. T2-weighted images were useful in differentiating leiomyoma and adenomyosis. Leiomyomas appeared as well-circumscribed nodules with sharp margins, while adenomyosis was seen as a low signal intensity area with an irregular border extending beneath the endometrium. b. In endometrial carcinoma, endometrial thickening with a high signal intensity was a characteristic of T2-weighted images, the maximal thickness being 16.5 +/- 6.9 mm. Moreover, endometrial carcinomas invading over 1/3 of the myometrium showed the following features: (1) The ratio of maximal endometrial thickness to uterine cross sectional diameter was over 50%. (2) The minimal myometrial thickness was under 5.0 mm. (3) The minimal to maximal myometrial thickness ratio was under 50%. Furthermore, cervical extension could be detected in all cases of endometrial carcinoma extending to the myometrium in T2-weighted images.

Adult↗
PubMed1990

[Fundus video fluorescein angiography with low steady light].

To decrease both the intensity of the exciting light and the amount of sodium fluorescein, we attached a compact image intensifier incorporating a microchannel plate with a fundus photoscope and tried to record video-fluorescein angiography with low steady light. We preliminarily examined the relationships of exciting and emitted light intensity with various concentrations of sodium fluorescein. The strongest fluorescence was obtained with a concentration of 0.01 mg/ml solution of sodium fluorescein. When the compact image intensifier was attached to the equipment, the exciting light intensity could be decreased to 1/300 with an exciting filter of lambda max of 486 nm. When sodium fluorescein of 0.01 mg/ml solution was injected directly into the heart of Rana catesbeiana, complete video-fluorescein angiography with sufficient brightness and resolution was possible. With the same machine, we recorded video-fluorescein angiography in a normal human subject with injection of 5 ml of 10% sodium fluorescein. The ordinary observing light of the machine was strong enough for video-recording. This exciting light intensity caused no trouble and elicited no complaint from the examinee. These results showed that the use of a compact image intensifier incorporated microchannel plate with a fundus photoscope made it possible to record video-fluorescein angiography and to decrease exciting light intensity and the amount of fluorescein dye. This means that light damage to photoreceptors by exciting light and problems induced by allergic reaction with fluorescein dye might be decreased. These aspects might be very important to obtain information about both retinal circulation and disruption of the blood-retinal barrier and also to perform safe fluorescein angiography examination.

Animals↗