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K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 163 records · Page 9Linked to original sources
PubMed1995

Apolipoprotein A-II gene and development of amyloidosis and senescence in a congenic strain of mice carrying amyloidogenic ApoA-II.

BACKGROUND: Apolipoprotein A-II (ApoA-II), a major apoprotein of serum high density lipoprotein (HDL) deposits as an amyloid fibril (AApoAII) in murine senile amyloidosis. Type C ApoA-II gene (Apoa2c) in the SAMP1 strain of mice, a murine model of severe senile amyloidosis and accelerated senescence was transferred on the genetic background of the SAMR1 strain, in which senile amyloidosis is rare and has a normal aging process, and a congenic strain of mouse (R1.P1-Apoa2c) was developed (Higuchi K, Kitado H, Kitagawa K, Kogishi K, Naiki H, Takeda T. FEBS Lett 1993;317:207-10). EXPERIMENTAL DESIGN: We identified AApoAII amyloid deposits in the 14-month-old congenic R1.P1-Apoa2c strain and compared these findings with the deposits in the progenitor SAMP1 and SAMR1 strains. The progression of senescence was estimated using a grading system and the age-associated changes in the metabolism of ApoA-II and HDL were investigated in the three strains of mice. RESULTS: At 14 months of age, severe amyloid deposition as compared with the donor SAMP1 strain was present in the congenic R1.P1-Apoa2c strain, but AApoAII was not evident in the progenitor SAMR1 strain which has type B ApoA-II. No obvious differences in the progression of senescence were observed between the R1.P1-Apoa2c and SAMR1 strains. In the R1.P1-Apoa2c strain, the serum HDL-cholesterol concentrations decreased in parallel with ApoA-II levels with advancing age and the decrease was much accelerated compared with the decrease seen in SAMR1 mice. CONCLUSIONS: Based on these results, we propose that the genetic type of ApoA-II plays an important role in the development of senile amyloidosis and age-associated changes in HDL metabolism. However, it has a minor role in the accelerated senescence in the mouse strains we used.

Aging↗
PubMed1995

[A case of Rendu-Osler-Weber syndrome and pulmonary arteriovenous fistula].

A 65-year-old man with Rendu-Osler-Weber syndrome was admitted to the department of brain surgery at our hospital because of left hemiplegia and a right cerebral mass seen on a computerized tomogram of the brain. A brain abscess was found during surgery. Then the patient had pneumonia. He received antibiotics and recovered, but his PaO2 remained low. He was transferred to our department for evaluation of hypoxia. Thoracic computerized tomography showed a nodular lesion connected to a vascular shadow. Angiographic examination showed a pulmonary arteriovenous fistula and other vascular abnormalities. He was not dyspneic or cyanotic, but his hypoxia, low diffusing capacity, and brain abscess were thought to be caused by the pulmonary arteriovenous fistula. The fistula was embolized with coils via a percutaneous catheter, after which oxygenation and diffusing capacity improved.

Aged↗
PubMed1994

Proteolipid protein interactions in transfectants: implications for myelin assembly.

The proteolipid proteins (PLP and DM20) are major constituents of CNS myelin, but how they are delivered to and organized within the oligodendrocyte plasma membrane is incompletely understood. We have expressed both PLP and DM20 singly or together in a host cell line, HeLa. In either DM20 or PLP transfectants, at early time points (24 hours), the expressed proteins are found within intracellular compartments. In DM20 transfectants, the protein is delivered to the plasma membrane by 48 hours. In HeLa cells, PLP remains intracellular when expressed in the absence of DM20; only when it is coexpressed with DM20 is it transported to the plasma membrane. In cotransfectants, PLP can also be localized to organelles involved in both the protein biosynthetic and the endocytic pathways. Since, in HeLa cells at least, the delivery of PLP to the plasma membrane is facilitated by the coexpression of DM20, we suggest that the two proteins interact intracellularly to form a complex. In some PLP/DM20 cotransfectants, the proteolipids are concentrated in regions of cell-cell contact. The regional accumulation of these proteins at cell-cell interfaces is highly reminiscent of the behavior in transfected cells of another myelin protein, P0, and certain cadherin polypeptides, both of which have readily demonstrable membrane adhesive properties. Our data suggests that at certain stoichiometric ratios, proteolipids can become stabilized at cell surfaces to form adhesive bonds.

Animals↗
PubMed1994

Adamantane as a brain-directed drug carrier for poorly absorbed drug. 2. AZT derivatives conjugated with the 1-adamantane moiety.

Five AZT (azidothymidine) prodrugs conjugated with the 1-adamantane moiety via an ester bond were synthesized to improve the transport of AZT into the central nervous system (CNS). In in vitro degradation studies with rat and human plasma, it was demonstrated that the prodrugs were degraded enzymatically and converted quantitatively to their parent drug. AZT. As assessed by octanol-buffer partitioning, the prodrugs were much more lipophilic than AZT and were expected to penetrate the blood-brain barrier (BBB) readily. In in vivo studies, in which the prodrugs were administered intravenously to rat, the prodrugs in brain tissue were detected at 7-18 times higher concentrations than AZT in spite of the negligible amount of the prodrug in the cerebrospinal fluid. These results indicate that the introduction to AZT of the 1-adamantane moiety results in the enhancement of the BBB penetration. This pharmaceutical approach would be beneficial for the efficient treatment of the CNS infection by human immunodeficiency virus.

Adamantane↗
PubMed1994

Skin permeability of various drugs with different lipophilicity.

The in vitro and in vivo skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0.95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle. The ethanol/panasate 800 (40/60) binary vehicle remarkably improved the in vitro skin permeability of the drugs across excised hairless mouse skin compared with ethanol or panasate 800 as single vehicles. The in vivo skin permeability of the large majority of the drugs across abdominal rat skin also showed high permeation rates and short lag times. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/panasate 800 (40/60) binary vehicle indicated parabolic shapes with their peaks at much greater hydrophilic range (log P: -0.88 for in vitro, -0.83 for in vivo) compared with other past references (log P: 2-3). The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/panasate 800 (40/60) lipophilic binary vehicle would be a good candidate as a vehicle for future clinical application of hydrophilic drugs.

Animals↗
PubMed1994

Tissue lipoproteins revisited: new proteolipid protein gene family members in elasmobranchs.

The proteolipids (PLPs) are abundant components of mammalian CNS myelin. Recombinant DNA methodologies have enabled us to search for evolutionary antecedents of PLP/DM20. Polymerase chain reactions of Torpedo and Squalus brain cDNA were performed with degenerate primers designed according to the mammalian PLP/DM20 sequence. Three DM20-related products (DM alpha, DM beta, and DM gamma) were amplified; no cDNAs containing the PLP-specific segment were found. Regions of the DM alpha and DM gamma are similar to the pore-forming segments of certain ligand-gated channels. In embryonic Squalus CNS, DM alpha and DM gamma appear to be co-expressed with P0. Antiserum raised against Torpedo DM alpha recognizes a protein in mouse CNS myelin, demonstrating that at least one of the newly recognized fish DMs is also in mammals. Our data, as well as that of other laboratories, supports the existence of a ubiquitously expressed proteolipid gene family.

Amino Acid Sequence↗
PubMed1994

Enhanced attachment and elastase-releasing capacity of neutrophils after surgery.

Perioperative changes in neutrophil attachment level and neutrophil elastase-releasing capacity were examined in patients who underwent surgery for either esophageal or gastric cancer. The neutrophil attachment level was significantly increased in both groups to approximately three times that of the preoperative value. The elastase-releasing capacity of nonstimulated neutrophils was not significantly changed, but it was significantly increased in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). Moreover, both neutrophil attachment and elastase-releasing capacity of FMLP-stimulated neutrophils were more enhanced in patients with postoperative complications than in patients without complications. Peak levels of serum interleukin 6, serum alpha 1 proteinase inhibitor, and plasma neutrophil elastase were also significantly higher in patients with postoperative complications than in patients without. These results suggest that during the postoperative period, neutrophils may be primed and activated in response to inflammatory mediators such as cytokines, and that such an alteration of neutrophil functions may reflect the extent of inflammation and may, at times, be implicated in postoperative complications.

Aged↗
PubMed1994

A new gerbil model of hindbrain ischemia by extracranial occlusion of the bilateral vertebral arteries.

A new gerbil model of hindbrain ischemia was induced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra. Carbon black studies, performed at 5 min after occlusion, revealed that the pons-medulla oblongata, and the cerebellum were quite ischemic in all animals. Cardiovascular changes in mean arterial blood pressure (MABP) and heart rate were recorded until 30 min after occlusion, and revealed that the typical cerebral ischemic response (i.e., abrupt increase in MABP, bradycardia, and apnea) was elicited in all animals (n = 10). Thirty minutes after occlusion, animals (n = 4) were decapitated and immersion-fixed. Brain sections were stained with hematoxylin-eosin (HE) and also immunostained for microtubule-associated protein 2 in order to evaluate ischemic neuronal damage from 30 min of ischemia. By HE staining, ischemic lesions were detected bilaterally in the oculomotor, the trigeminal motor, the lateral vestibular, and the cerebellar interpositus nucleus. In addition, immunostaining revealed ischemic lesions in several other hindbrain areas. In conclusion, we could successfully establish a new gerbil model of hindbrain ischemia. Carbon black perfusion and hemodynamic studies revealed that severe and reproducible hindbrain ischemia was produced. By histopathological examination, we could also clearly demonstrate symmetrical ischemic lesions in several hindbrain areas.

Animals↗
PubMed1994

Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus.

Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5; 0%), and rare in those infected with hepatitis C virus (1/9; 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus.

Adult↗
PubMed1994

Modification of strain-specific femoral bone density by bone marrow-derived factors administered neonatally: a study on the spontaneously osteoporotic mouse, SAMP6.

SAMP6 is a recently developed strain of osteoporotic mice, and SAMP2 is a control for SAMP6 and has a higher peak bone mass. The bone mass of SAMP6 was increased until 2 months of age when a lysate of cells derived from the bone marrow of SAMP2 was injected at 1 or 4 days of age, but it was not increased when the lysate was injected at 21 days of age. No effect on bone mass was observed when lysates of other cells, bovine serum albumin or heat-inactivated lysate of bone marrow-derived cells of SAMP2, were injected. The ability to increase bone mass was not in the supernatant but in the pellet obtained by ultracentrifugation (105,000 g) of the lysate of bone marrow-derived cells of SAMP2. The lysate did not change the osteoclast surface but changed the appositional bone formation. In conclusion, the lysate of cells derived from the bone marrow of SAMP2 contains factors which can increase the bone mass of SAMP6, and these factors are present in the pellet obtained by ultracentrifugation.

Animals↗
PubMed1994

Immunohistochemical study of alpha 1-5 chains of type IV collagen in hereditary nephritis.

The distribution of alpha 1-5 chains of type IV collagen [alpha 1-5(IV)] in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM) of 23 families with hereditary nephritis was examined by indirect immunofluorescence. These families were divided into three clinicopathological groups. Group I (10 families) patients showed a widespread "basket weave" pattern of the GBM and a family history of nephritis was present. Group II (6 families) patients showed a widespread "basket weave" change without a family history of nephritis. Group III (7 families) patients showed a widespread attenuation of the GBM but no "basket weave" change, and had a family history of nephritis and chronic renal failure. alpha 1(IV) and alpha 2(IV) were present in all affected and unaffected family members and controls. All normal family members and controls expressed alpha 3(IV), alpha 4(IV) and alpha 5(IV) in the GBM and alpha 5(IV) in the EBM in a diffuse pattern. All group I families and three of the group II families exhibited complete loss of the alpha 5(IV) antigen from the GBM and EBM in male patients, and segmental loss of the alpha 5(IV) antigen in female patients. In these families the alpha 3(IV) and alpha 4(IV) antigens were completely lost from the GBM in male patients with severe nephritis, whereas alpha 3(IV) alpha 4(IV) were present but diminished in male patients with mild nephritis. Three group II and all group III families expressed the alpha 3-5(IV) antigens in an identical manner to that of normal controls. These findings indicate that the heterogeneity of hereditary nephritis reflects a variety of aberrant expression patterns of alpha 3-5(IV) and that immunohistochemical examination of alpha 5(IV) in the EBM is a useful method for the diagnosis of X-linked Alport syndrome.

Adult↗
PubMed1994

Solid-phase synthesis of cionin, a protochordate-derived octapeptide related to the gastrin/cholecystokinin family of peptides, and its mono-tyrosine-sulfate-containing derivatives.

Cionin, a protochordate-derived octapeptide amide related to the gastrin/cholecystokinin family of peptides, contains two consecutive tyrosine sulfate residues. In order to gain insight into the role of the respective tyrosine sulfate residue in biological activity, cionin and its derivatives in which one of the two tyrosine sulfate residues was replaced by tyrosine, were prepared by two Fmoc-based solid-phase approaches. In approach (1) Fmoc-Tyr(SO3Na)-OH was employed as a building block to assemble the Tyr(SO3Na)-containing peptide-resin, and a global deprotection/cleavage was conducted with 90% aqueous TFA in the presence of m-cresol and 2-methylindole at 4 degrees C. In approach (2) the Tyr(Msib) [Msib = p-(methylsulfinyl)benzyl] derivative was used for the peptide-chain assembly to achieve sulfation on the selective Tyr residue. Partially protected peptide with the Msib/Msz protecting groups [Msz = p-(methylsulfinyl)benzyloxycarbonyl], obtained after peptide-resin cleavage, was treated with DMF-SO3 complex in the presence of ethanedithiol to achieve the sulfation of free Tyr residue and the reduction of the Msib/Msz groups to TFA-labile Mtb/Mtz groups [Mtb = p-(methylthio)benzyl, Mtz = p-(methylthio)benzyloxycarbonyl]. Final deprotection of the Mtb/Mtz groups with 90% aqueous TFA in the presence of m-cresol and 2-methylindole gave the desired cionin derivative, which contains the tyrosine sulfate residue at the selective position. Yields obtained with approach (2) were considerably higher than those obtained with approach (1). Cionin and mono-Tyr(SO3H)-containing derivatives were assayed on exocrine pancreas in dogs.

Amino Acid Sequence↗
PubMed1994

Histological features of palatine tonsils in pustulosis palmaris et plantaris: a morphometric study.

The morphological expression of the immune response of palatine tonsils obtained from patients with pustulosis palmaris et plantaris (PPP) was investigated by morphometry in conjunction with immunohistochemistry. First, to differentiate the histological features of tonsils between PPP and habitual tonsillitis, each extent of the T cell dependent areas (T nodules), B cell dependent areas (lymph follicles), germinal centers, mixed areas of T cells and B cells, and lacunar epithelium was measured and compared on 38 patients with PPP and 47 with habitual tonsillitis, respectively. The most remarkable findings in PPP were enlargement of the secondary T nodules, and atrophy of the lymph follicles with a decrease in number of the germinal center cells and fibrosis. These changes of lymph follicles were similar to those in the older patients with habitual tonsillitis, which suggests the intensely advanced stage of the immune response within the tonsils. Second, the histological structures of the tonsils of 15 tonsillectomy effective cases (88.2%) was compared with those of two non-effective cases in curing skin lesions. The histological structure in the non-effective cases was very similar to that in habitual tonsillitis cases. This indicates that the histological findings may be useful in predicting the effects of tonsillectomy on PPP.

Adult↗
PubMed1994

Pseudolesion in segment IV of the liver at CT during arterial portography: correlation with aberrant gastric venous drainage.

PURPOSE: To analyze the correlation between pseudolesions seen in segment IV of the liver and aberrant gastric venous drainage (AGVD). MATERIALS AND METHODS: Twenty-two patients with a pseudolesion in the posterior edge of segment IV of the liver (group A) and 100 randomly selected patients without pseudolesions (group B) underwent computed tomography during arterial portography (CTAP) and hepatic arteriography. The frequency of the visualization of AGVD to segment IV was compared for groups A and B. RESULTS: AGVD was seen at arteriography in 18 of 22 patients in group A. None of the patients in group B had AGVD. The difference in the frequency of angiographically visible AGVD was statistically significant (chi 2 test, P < .01). CONCLUSION: AGVD is the main cause of pseudolesions in the posterior edge of segment IV of the liver.

Diagnosis, Differential↗
PubMed1994

Segmental iron deposition in the liver due to decreased intrahepatic portal perfusion: findings at MR imaging.

PURPOSE: To evaluate the causes of intrahepatic segmental areas of signal hypointensity [corrected] on T1- and T2-weighted spin-echo (SE) and gradient-echo (GRE) magnetic resonance (MR) images. MATERIALS AND METHODS: Six patients in whom wedge-shaped hypointense areas were seen on hepatic MR images underwent examination with ultrasound (US), computed tomography (CT), angiography, and CT during arterial portography (CTAP). Histologic examination was performed in three patients. RESULTS: The affected liver parenchymas were best depicted as segmental or lobar hypointense areas on GRE images. Angiography and CTAP revealed that portal blood supply to the hypointense areas was absent or decreased due to portal vein tumor thrombus and arterioportal shunt (n = 1), compression of a portal branch by tumor (n = 2), portal vein thrombosis (n = 1), or arterioportal shunt (n = 2). Iron deposition in the hepatocytes was evident in all three patients with histologic correlation. CONCLUSION: Segmental signal hypocoagulability was generally due to hepatocyte iron deposition and was accompanied and possibly caused by a disturbance in portal flow.

Adult↗
PubMed1994

A cytosolic peptide potentiates the GTP effect on beta-adrenergic response of adenylate cyclase.

A cytosolic peptide-GTP complex that stimulates l-isoproterenol-responsive adenylate cyclase activity was identified in the rat liver. The peptide component was purified and characterized with regard to its interaction with GTP. The peptide was isolated as a complex form with GTP on a Sephadex G-25 column in 1 mM NaHCO3, and was purified as a dissociated form, with relative molecular weight (M(r)) approximately 3,000 and GTP-binding ability, in 200 mM ammonium acetate. The purified peptide alone displayed little stimulatory effect on adenylate cyclase activity, but its reassociated form with GTP clearly enhanced the effect of GTP on the enzyme activity. The isoproterenol competition curve using l-[3H]dihydroalprenolol as an antagonist ligand shifted to lower affinity by the addition of the peptide reassociated with GTP (16.5-fold shift), whereas the same concentration of GTP (1 microM) or the peptide alone had little or no effect (1.5- or 0.9-fold shift, respectively). Furthermore, the peptide enhanced the GTP effect in response to l-isoproterenol but not to glucagon, prostaglandin E1, or fluoride. These results suggest that the cytosolic peptide potentiates the effect of GTP on the agonist-beta-adrenergic receptor-stimulatory guanine nucleotide-binding regulatory component of the adenylate cyclase ternary complex.

Adenylyl Cyclases↗
PubMed1994

Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells.

We previously reported the massive secretion of brain natriuretic peptide (BNP) from human amnion cells and suggested the possible role of BNP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measured the BNP level in the culture medium of amnion cells by RIA after incubation in the presence of various substances. Among the agents examined, cortisol (1 x 10(-7) to 1 x 10(-6) mol/L), dexamethasone (1 x 10(-8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnion cells in a dose-dependent manner. By contrast, transforming growth factor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion was abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF beta in human amniotic fluid (approximately 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cortisol, EGF and TGF beta, all at the concentrations physiologically present in human amniotic fluid, implies a physiological role of BNP secretion from amnion cells in the pregnant uterus.

Amnion↗