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Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 73 records · Page 4Linked to original sources
PubMed2003

Interferon (IFN)-beta 1a and IFN-beta 1b block IFN-gamma-induced disintegration of endothelial junction integrity and barrier.

Recent clinical trials indicate the efficacy of interferon (IFN)-beta 1b in reducing relapse rate in relapsing-remitting multiple sclerosis (MS), whereas a surge of IFN-gamma precedes and provokes acute relapses. Disruption of the cerebral endothelial barrier and transendothelial migration of inflammatory cell migration into the brain play a significant role in pathogenesis of MS and may be driven by this surge in IFN-gamma. However, the molecular mechanisms underlying the beneficial effects of IFN-beta 1b against the deleterious effects of IFN-gamma on the barrier formed by the junctional proteins remain to be characterized. The authors investigated the effects of IFN-beta 1b, IFN-beta 1a, and IFN-gamma on the integrity of two endothelial junctional proteins, occludin and vascular endothelial-cadherin (VE-cadherin). Human umbilical vein endothelial cell (HUVEC) layers were treated with IFN-beta 1b, IFN-beta 1a, IFN-gamma, IFN-beta 1b plus IFN-gamma, or IFN-beta 1a plus IFN-gamma. IFN-beta 1b, IFN-beta 1a, and IFN-gamma effects on occludin and VE-cadherin integrity and electrical resistance were assessed by Western blotting and immunofluorescence. IFN-gamma significantly reduced occludin expression and produced gaps in endothelial monolayers. VE-cadherin expression was decreased to a lesser extent in endothelial cells exposed to IFN-gamma. IFN-beta 1b significantly attenuated the IFN-gamma-induced decrease in occludin and VE-cadherin expression. The protective effects of IFN-beta 1a on IFN-gamma-treated endothelial cells were similar to those of IFN-beta 1b. IFN-gamma also significantly reduced endothelial monolayer electrical resistance; this effect was blocked by either IFN-beta 1a or IFN-beta 1b. IFN-beta 1a and IFN-beta 1b effectively prevent the IFN-gamma-induced disintegration of the endothelial tight junctions and sustain barrier against the effects of IFN-gamma. The protective effects of IFN-beta on occludin and VE-cadherin stability appear to represent molecular mechanisms for the therapeutic effects of the IFN-beta on blood brain barrier in MS.

Antigens, CD↗
PubMed2003

Vasculitis in a dog resembling isolated angiitis of the central nervous system in humans.

An 1-year-old dog succumbed to a seizure disorder of 18 days duration. At necropsy, an area of hemorrhage and discolored parenchyma was identified in the left pyriform lobe of the brain. Microscopic examination revealed a localized, necrotizing vasculitis with associated cerebral necrosis. Vasculitis was not present in other organs. This presentation is consistent with isolated central nervous system (CNS) angiitis, a rare form of vasculitis in humans.

Animals↗
PubMed2003

[Intractable pneumothorax for pleuritis carcinomatosis effectively treated with bronchial embolization: report of a case].

A 57-year-old female was admitted with compliant of cough and body weight loss. Chest X-ray and thoracic computed tomography (CT) scan revealed a collapsed lung and pleural effusion. We diagnosed a pleulitis carcinomatosis. After right chest tube drainage was performed, she developed right intractable pneumothorax. It was occluded endobronchially by the placement of vascular embolization coils and histoacryl. This method is thought to be an effective treatment for intractable pneumothorax patients in endstage of lung cancer.

Embolization, Therapeutic↗
PubMed2002

Properties of utricular-activated vestibular neurons that project to the contralateral vestibular nuclei in the cat.

The properties of utricular (UT)-activated vestibular neurons that send axons to the contralateral vestibular nuclei (commissural neurons) were investigated intracellularly or extracellularly in decerebrate cats. A total of 27 vestibular neurons were orthodromically activated by stimulation of UT nerves and antidromically activated by stimulation of the contralateral vestibular nuclei. All neurons tested were classified as vestibulospinal (VS), vestibulooculospinal (VOS), vestibuloocular (VO), and unidentified vestibular neurons (V) after antidromic stimulation of the spinal cord and oculomotor/trochlear nuclei. Most UT-activated commissural neurons (20/27) received monosynaptic inputs. Twelve of 27 commissural neurons were located in the medial vestibular nucleus, 5 were in the lateral vestibular nucleus, 10 were in the descending vestibular nucleus, and no commissural neurons were recorded in the superior vestibular nucleus. Seven of 27 neurons were commissural VS neurons, 9 of 27 were commissural VOS neurons, and 11 of 27 were commissural V neurons. No commissural VO neurons were found. All VOS neurons and 3 VS neurons issued descending axons via the medial vestibulospinal tract. We also studied convergent inputs from the posterior semicircular canal (PC) nerve onto UT-activated commissural neurons. Five of 27 UT-activated commissural neurons received converging inputs from the PC nerves.

Animals↗
PubMed2002

Convergence of the anterior semicircular canal and otolith afferents on cat single vestibular neurons.

The convergence between the anterior semicircular canal (AC) and utricular (UT) inputs, as well as the convergence between the AC and saccular (SAC) inputs in single vestibular neurons of decerebrated cats were investigated. Postsynaptic potentials were recorded intracellularly after selective stimulation of each pair of vestibular nerves AC/UT or AC/SAC. Neurons were recorded from the central parts of the vestibular nuclei, where the otolith afferents mainly terminate. Of a total of 105 neurons that were activated after stimulation of the AC and UT nerves, 42 received convergent inputs. Thirty-eight of these neurons received excitatory inputs from both afferents. Convergent neurons were further classified into vestibulospinal (n=28) and vestibulooculospinal (n=6) neurons by antidromic activation from the border between the C1 and C2 spinal cord and the oculomotor or trochlear nucleus. Eight neurons that were not antidromically activated from either site were classified as vestibular neurons. Forty three percent of the convergent vestibulospinal neurons and most of the convergent vestibulooculospinal neurons projected to the spinal cord through the medial vestibulospinal tract. The remaining vestibulospinal and vestibulooculospinal neurons descended through the ipsilateral lateral vestibulospinal tract. Of a total of 118 neurons that were activated after stimulation of the AC and/or SAC nerves, 51 received convergent inputs (27 vestibulospinal, 4 vestibulooculospinal, 5 vestibuloocular and 15 vestibular neurons). Forty-two of the convergent neurons received excitatory inputs from both afferents. Thirty seven percent of the convergent vestibulospinal neurons and all of the convergent vestibulooculospinal neurons projected to the spinal cord through the medial vestibulospinal tract. The remaining vestibulospinal and vestibulooculospinal neurons descended through the ipsilateral lateral vestibulospinal tract.

Afferent Pathways↗
PubMed2002

Measurements of cosmic-ray low-energy antiproton and proton spectra in a transient period of solar field reversal.

The energy spectra of cosmic-ray low-energy antiprotons ( *p's) and protons ( p's) have been measured by BESS in 1999 and 2000, during a period covering reversal at the solar magnetic field. Based on these measurements, a sudden increase of the *p/p flux ratio following the solar magnetic field reversal was observed, and it generally agrees with a drift model of the solar modulation.

Journal Article↗
PubMed2002

Effect of asymmetric modification on the conformation of ascidiacyclamide analogs.

Ascidiacyclamide (ASC), cyclo(-Ile1-Oxz2-d-Val3-Thz4-)2 (Oxz=oxazoline and Thz=thiazole) has a C2-symmetric sequence, and the relationships between its conformation and symmetry have been studied. In a previous study, we performed asymmetric modifications in which an Ile residue was replaced by Gly, Leu or Phe to disturb the symmetry [Doi et al. (1999) Biopolymers49, 459-469]. In this study, the modifications were extended. The Ile1 residue was replaced by Gly, Ala, aminoisobutyric acid (Aib), Val, Leu, Phe or d-Ile, and the d-Val3 residue was replaced by Val. The structures of these analogs were analyzed by X-ray diffraction, 1H NMR and CD techniques. X-Ray diffraction analyses revealed that the [Ala1], [Aib1] and [Phe1]ASC analogs are folded, whereas [Val1]ASC has a square form. These structures are the first examples of folded structures for ASC analogs in the crystal state and are similar to the previously reported structures of [Gly1] and [Phe1]ASC in solution. The resonances of amide NH and Thz CH protons linearly shift with temperature changes; in particular, those of [Aib1], [d-Ile1] and [Val3]ASCs exhibited a large temperature dependence. DMSO titration caused nonlinear shifts of proton resonances for all analogs and largely affected [d-Ile1] and [Val3]ASCs. A similar tendency was observed upon the addition of acetone to peptide solutions. Regarding peptide concentration changes, amide NH and Thz CH protons of [Gly1]ASC showed a relatively large dependence. CD spectra of these analogs indicated approximately two patterns in MeCN solution, which were related to the crystal structures. However, all spectra showed a similar positive Cotton effect in TFE solution, except that of [Val3]ASC. In the cytotoxicity test using P388 cells, [Val1]ASC exhibited the strongest activity, whereas the epimers of ASC ([d-Ile1] and [Val3]ASCs), showed fairly moderate activities.

Amino Acid Substitution↗
PubMed2002

Lectins can reverse the distal intestinal atrophy associated with elemental diets in mice.

BACKGROUND: Elemental diets cause intestinal atrophy and reduced intestinal integrity, which can lead to significant increases in intestinal permeability and bacterial translocation. Recently, several lectins have been shown to have trophic effects on the intestine. AIMS: We examined the effects of concanavalin-A and phytohaemagglutinin on cell proliferation and crypt fission throughout the intestine of mice fed on elemental diets. METHODS: Mice were randomized to chow fed, elemental diet, elemental diet plus concanavalin-A and elemental diet plus phytohaemagglutinin groups. Cell proliferation and crypt fission were estimated in microdissected crypts. Plasma gastrin and enteroglucagon levels were measured by radioimmunoassay. RESULTS: Elemental diet feeding significantly decreased cell proliferation and crypt fission of the middle and distal small intestine and throughout the colon. Phytohaemagglutinin significantly increased the weight of the intestine, but concanavalin-A had little effect. Cell proliferation in the small intestine was significantly increased by both lectins. However, in the stomach and colon, only phytohaemagglutinin increased proliferation. Crypt fission in the colon was dramatically increased by phytohaemagglutinin. Phytohaemagglutinin increased the plasma gastrin level, but not the enteroglucagon level. CONCLUSIONS: Lectins have significant trophic effects on the small intestine and colon of mice fed elemental diets, and these actions vary between different sites in the gastrointestinal tract.

Animals↗
PubMed2002

The renal structure in an Asian elephant (Elephas maximus).

The renal structure of a female Asian elephant (Elephas maximus) was observed in both macroscopic and light microscopic levels. The left kidney was elongated-ellipse in shape, whereas the right appeared round. The left kidney was 31 cm in cranio-caudal length, 21 cm in medio-lateral length, and 2950 g in weight. The right kidney was 34 cm in cranio-caudal length, 22 cm in medio-lateral length, and 3250 g in weight. The external appearance showed the six separated renal lobes in both sides of the kidney. The four pairs of the lobes were fused in the deepest region in both sides of kidney, so we considered it as an incompletely lobated kidney in this species. We observed the proximal and distal urinary tubules in histological sections. Many renal corpuscles consisted of the glomerulus and Bowman's capsule. Many mesangial cells and some podocytes were confirmed in each glomerulus; however, Bowman's capsules were larger than those in other mammalian species.

Animals↗
PubMed2002

Comparative functional morphology of the masticatory apparatus in the long-snouted crocodiles.

The masticatory muscles and their related structures of the skull were observed in the Indian gavial (Gavialis gangeticus), the false gavial (Tomistoma schlegelii), and the African slender-snouted crocodile (Mecistops cataphractus) to detail some morphological differences in comparison with the other crocodile species, and to compare and elucidate the functional strategy of themasticatory apparatus in these long-snouted species. The Musculus pterygoideus posterior was relatively smaller in the three species compared with many short-snouted crocodiles. It suggests that the masticatory power in fish-eating long-snouted species is not so high as in the short-snouted crocodiles, while the masticatory muscles were morphologically different among the three long-snouted species as follows. The M. pterygoideus posterior of the false gavial was extended in the lateral side of the lower jaw unlike the Indian gavial. The M. pseudotemporalis and the Fenestra supratemporalis were largely developed in the Indian gavial, however we suggest that the other two species possess the weak bundles in this muscle. The false gavial and the African slender-snouted crocodile have the pterygoid bone well-developed extending dorso-ventrally and it is suggested that the M. adductor mandibulae posterior attached to the pterygoid bone may be much larger than the Indian gavial. These data morphologically clarify the masticatory mechanism in the long-snouted crocodiles different from the short-snouted species, and demonstrate that the evolutional strategy to share the functional role in the masticatory muscles have been differently established between the Indian gavial and the other two species. We also obtained the morphological data in the fossil skull of the Machikane crocodile (Toyotamaphymeia machikanense) and concluded from the fossil characters that the considerable developments of the M.pterygoideus posterior and the M.pseudotemporalis in this species had not morphologically been consistent with both the Indian and false gavials.

Alligators and Crocodiles↗
PubMed2002

Biliary papillary neoplasm of the liver.

Biliary papillary neoplasia of the liver characterized by intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk has been sporadically reported, and includes intraductal growing cholangiocarcinoma and biliary papillomatosis. In addition, biliary papillary dysplasia and in situ and microinvasive carcinoma with papillary configuration reported in hepatolithiasis and in other chronic biliary diseases, could be included in this category. Usually, they arise in the intrahepatic large bile ducts, and the neoplastic and non-neoplastic parts of the intrahepatic biliary tree show saccular and segmental dilatation with mucin hypersecretion. This neoplasia frequently shows intraductal spreading and peribiliary glandular involvement. Acute repeated episodes of cholangitis or obstructive jaundice are a frequent clinical manifestation. Gastroenteric metaplasia with aberrant expression of cytokeratin 20, MUC2, MUC5AC, and/or MUC6, is frequent in the neoplastic parts, and biliary epithelial dysplasia with such metaplasia may give rise to in situ and then invasive carcinoma in hepatolithiasis. Interestingly, this type tends to contain foci of mucinous carcinoma elements, and this element may be predominant (mucinous carcinoma). Some may progress to "mucinous biliary cystadenocarcinoma" without ovarian mesenchymal stroma and with intraluminal continuous growth into the neighboring bile duct lumens. Interestingly, the biliary papillary neoplasm resembles histologically, phenotypically and clinically intraductal papillary mucinous neoplasm of the pancreas which is now being established as an infrequent, slow-growing pancreatic neoplasm. Recognition of such biliary papillary neoplasm with respect to the pancreatic equivalent may lead to a better understanding and further studies of the intrahepatic biliary neoplasm.

Aged↗
PubMed2001

Efficacy of double filtration plasmapheretic cross-circulation using a high permeability membrane between totally hepatectomized dogs and donor pigs.

BACKGROUND: Major obstacles to develop a bioartificial liver are xenogeneic immune reactions and viral infection from donor pigs. To solve these problems, we studied the effect of xenogeneic double filtration plasmapheretic cross-circulation (DFPCC) using a high performance semipermeable membrane on totally hepatectomized dogs. METHODS: Mongrel dogs, weighing 12-15 kg, underwent total hepatectomy in one stage (n=18). One hr after total hepatectomy, the femoral vein and the jugular vein were cannulated in both dogs and pigs by using the blood access catheter tubes that were connected to the DFPCC system. In the DFPCC circuit, filtrated dog plasma and pig plasma counterflowed in a hollow fiber cartilage at a rate of 25 ml/min for 6 hr and met through a semipermeable membrane with 100 kd nominal molecular weight cut-off (n=5). In control dogs, the circuit was not connected to the pig (n=13). RESULTS: In vitro mass transfer study suggested that very little immunoglobulins crossed the semipermeable membrane. During and after 6 hr of DFPCC, anhepatic dogs had significantly lower blood ammonia and aromatic amino acid levels than did controls. DFPCC-treated dogs demonstrated decreased intracranial pressure and survived significantly longer than control dogs (20.75+/-3.80 hr vs. 14.75+/-1.30 hr, P<0.05). Histology showed no xenogeneic rejection in both dogs and pigs. CONCLUSIONS: Our DFPCC systems with a high permeability membrane demonstrated detoxification-function and contributed to intracranial decompression and longer animal survivals without adverse immune reaction and the possibility of zoonosis.

Animals↗
PubMed2001

KNI-272, a highly selective and potent peptidic HIV protease inhibitor.

Kynostatin [KNI-272; systematic name: 3-[3-benzyl-2-hydroxy-9-(isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4,7-diazanonanoyl]-N-tert-butyl-1,3-thiazolane-4-carboxamide], a highly selective and potent HIV protease inhibitor containing allophenylnorstatin [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], has been crystallized as the hydrate, C(33)H(41)N(5)O(6)S(2) x 0.803H(2)O, from aqueous hexylene glycol. The observed disorder of the phenyl group in the structure is related to the mode of hydration. The backbone conformation of the molecule is twisted and the overall conformation of the free inhibitor is similar to that observed in its complex with HIV protease.

Crystallography, X-Ray↗
PubMed2001

Antiparallel pleated beta-sheets observed in crystal structures of N,N-bis(trichloroacetyl) and N,N-bis(m-bromobenzoyl) gramicidin S.

Despite intensive efforts, the structures of gramicidin S (GS) [cyclo(-Val-Orn-Leu-d-Phe-Pro-)(2)] and its analogues have not been elucidated by the X-ray diffraction method, except for the GS-urea complex (Hull et al., Nature 275, 206-207, 1978; Tishchenko et al., Acta Cryst. D53, 151-159, 1997). We focused on the acetylation of GS to obtain suitable crystals for X-ray diffraction. The amino groups of Orn residues were capped with trichloroacetic and m-bromobenzoic acids. Both trichloroacetyl and m-bromobenzoyl GSs (TcGS and BzGS, respectively) are hydrophobic and their properties are similar to those of acetyl-GS (AcGS). Although it is well known that AcGS yields hexagonal crystals, TcGS and BzGS yield monoclinic and orthorhombic crystals in aqueous dimethylformamide solution, respectively. Their cell volumes were approximately one-fourth or one-eighth of the hexagonal cell volume. The crystal structures of TcGS and BzGS were determined as the first examples of acetylated GS analogues: TcGS, C(64)H(90)N(12)O(12)Cl(6). 3(C(3)H(7)NO), M(r) = 1651.47, monoclinic, P2(1), a = 15.4366(6) A, b = 18.5312(4) A, c = 16.4774(6) A, beta = 14.160(2) degrees, V = 4300.6(2) A(3), Z = 2; and BzGS, C(64)H(98)N(12)O(12)Br(2). 1.54(H(2)O), M(r) = 1535.21, orthorhombic, P2(1)2(1)2(1), a = 16.748(10) A, b = 18.834(5) A, c = 28.558(10) A, V = 9008(7) A(3), Z = 4. Both these peptide molecules formed an antiparallel pleated beta-sheet, and pseudo twofold symmetries existed in the repeated sequence. beta-Turns formed at the fragments of d-Phe-Pro were classified into type II' based on their characteristics. The peptide conformations of TcGS and BzGS were similar to each other, and these structural features agreed with those of structures proposed by the previous studies.

Bromobenzoates↗