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M Kan

Publications and source records attributed to M Kan.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Studies on surfactant replacement therapy in pediatric measles pneumonitis].

Measles pneumonitis, as well as encephalitis, is the most important complication associated with mortality in measles. Many medications including steroids and vitamin A have been applied to pediatric measles pneumonitis. However, the efficacy of such medication has not yet been established. This study is aimed at evaluating the effectiveness of surfactant replacement therapy in pediatric measles pneumonitis. Five patients (aged 1-2 years) with measles pneumonitis were transferred to our emergency center. On the transferred day, Surfactant-TA was administered by intratracheal method. After administration of surfactant, PaO2/FIO2 increased from 63.6 +/- 11.0 (mean +/- SE) to 206.2 +/- 54.1 in an hour and to 163.8 +/- 34.8 in 24. At the same time, the CO2 elimination and the dynamic compliance were improved. Because of these effects, the peak inspiratory pressure employed in mechanical ventilation could be reduced. It is concluded that surfactant replacement therapy can prevent the patients with measles pneumonitis from hypoxemia and ventilation-induced lung injury. However, further study is needed to maintain the improved oxygenation. Recently, it is reported that the effect of exogenous surfactant on oxygenation and activity of pulmonary neutrophils is regulated by the amount and/or concentration of administered surfactant. Therefore, it is an urgent issue to find out the optimum amount and concentration of exogenous surfactant used clinically.

Biological Products↗
PubMed1999

Requirement for anticoagulant heparan sulfate in the fibroblast growth factor receptor complex.

A divalent cation-dependent association between heparin or heparan sulfate and the ectodomain of the fibroblast growth factor (FGF) receptor kinase (FGFR) restricts FGF-independent trans-phosphorylation between self-associated FGFR and determines specificity for and mediates binding of activating FGF. Here we show that only the fraction of commercial heparin or rat liver heparan sulfate which binds to immobilized antithrombin formed an FGF-binding binary complex with the ectodomain of the FGFR kinase. Conversely, only the fraction of heparin that binds to immobilized FGFR inhibited Factor Xa in the presence of antithrombin. Only the antithrombin-bound fraction of heparin competed with (3)H-heparin bound to FGFR in absence of FGF, whereas both antithrombin-bound and unretained fractions competed with radiolabeled heparin bound independently to FGF-1 and FGF-2. The antithrombin-bound fraction of heparin was required to support the heparin-dependent stimulation of DNA synthesis of endothelial cells by FGF-1. The requirement for divalent cations and the antithrombin-binding motif distinguish the role of heparan sulfate as an integral subunit of the FGFR complex from the wider range of effects of heparan sulfates and homologues on FGF signaling through FGFR-independent interactions with FGF.

Animals↗
PubMed1999

Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase.

A divalent cation-dependent association between heparin or heparan sulfate and the ectodomain of the FGF receptor kinase (FGFR) restricts FGF-independent trans-phosphorylation and supports the binding of activating FGF to self-associated FGFR. Here we show that in contrast to heparin, cellular heparan sulfate forms a binary complex with FGFR that discriminates between FGF-1 and FGF-2. FGFR type 4 (FGFR4) in liver parenchymal cells binds only FGF-1, whereas FGFR1 binds FGF-1 and FGF-2 equally. Cell-free complexes of heparin and recombinant FGFR4 bound FGF-1 and FGF-2 equally. However, in contrast to FGFR1, when recombinant FGFR4 was expressed back in epithelial cells by transfection, it failed to bind FGF-2 unless heparan sulfate was depressed by chlorate or heparinase treatment. Isolated heparan sulfate proteoglycan (HSPG) from liver cells in cell-free complexes with FGFR4 restored the specificity for FGF-1 and supported the binding of both FGF-1 and FGF-2 when complexed with FGFR1. In contrast, FGF-2 bound equally well to complexes of both FGFR1 and FGFR4 formed with endothelial cell-derived HSPG, but the endothelial HSPG was deficient for the binding of FGF-1 to both FGFR complexes. These data suggest that a heparan sulfate subunit is a cell type- and FGFR-specific determinant of the selectivity of the FGFR signaling complex for FGF. In a physiological context, the heparan sulfate subunit may limit the redundancy among the current 18 FGF polypeptides for the 4 known FGFR.

Animals↗
PubMed1999

Fibroblast growth factor-10. A second candidate stromal to epithelial cell andromedin in prostate.

Fibroblast growth factor (FGF)-10, a homologue of FGF-7, is expressed significantly in normal rat prostate tissue, well differentiated rat prostate tumors with an epithelial and stromal compartment and only in derived prostate stromal cells in culture. Similar to FGF-7, recombinant rat FGF-10 was a specific mitogen for prostate epithelial cells. In contrast to FGF-7 which is widely expressed among stromal cells in tissues, the expression of FGF-10 correlated with the presence of stromal cells of muscle origin. Radioreceptor binding assays and covalent cross-linking analysis revealed that FGF-10 binds with an affinity equal to FGF-7 to resident epithelial cell receptor, FGFR2IIIb, but unlike FGF-7 also binds the IIIb splice variant of FGFR1. Analysis of mRNA expression by RNase protection revealed that, similar to FGF-7, the expression of FGF-10 was responsive to androgen in stromal cells from normal prostate and non-malignant differentiated tumors. Although FGF-10 cDNA exhibits a signal sequence for secretion, cultured stromal cells exhibit strictly a cell-associated FGF-10 antigen that correlates with an alternately translated intracellular isoform. FGF-10 requires 1.4 times higher NaCl for elution from immobilized heparin than does FGF-7 and binds to four times the number of sites on the pericellular matrix of epithelial cells. The results show that prostate stromal cell-derived FGF-10, like FGF-7, exhibits the properties of an andromedin which may indirectly mediate control of epithelial cell growth and function by androgen. Although FGF-10 and FGF-7 bind and activate the same resident epithelial cell receptor (FGFR2IIIb), differences in cell type of origin, compartmentation by alternate translation, the affinity for FGFR1IIIb, and access to FGFR by differential interaction with pericellular matrix heparan sulfate suggest they may play both independent and compensatory roles in prostate homeostasis.

Animals↗
PubMed1999

Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex.

The assembly and activation of oligomeric complexes of FGF, the transmembrane receptor kinase (FGFR), and heparan sulfate transmit intracellular signals regulating growth and function of cells. An understanding of the structural relationships between the three subunits and their redundancy and specificity is essential for understanding the ubiquitous FGF signaling system in health and disease. Previously, we reported that a primary heparin or heparan sulfate binding site resides in a distinct sequence in immunoglobulin (Ig)-like module II of the three modules of FGFR. Here we report that in the absence of flanking sequences, isolated Ig module II of FGFR1 supports the binding of FGF-1, FGF-2, and FGF-7 in respective order of affinity. None of the three FGFs detectably bind Ig module I or the IIIb and IIIc splice variants of Ig module III in the absence of flanking sequences. Ig module I and the C-terminus of Ig module III are dispensable for high-affinity binding of FGF-1, FGF-2, and FGF-7. Alterations in highly conserved Ig module II in the heparin binding domain and substitution of individual sequence domains spanning the entire sequence of Ig module II with those from Ig module I obliterated FGF binding. Addition of a specific number of FGFR sequences to the C-terminus of Ig module II resulted in a gain in affinity for FGF-7. Several site-specific alterations in the C-terminus of full-length FGFR1IIIc, an isoform that otherwise absolutely rejects FGF-7, resulted in gain of FGF-7 binding. These results suggest that a complex of Ig module II and heparan sulfate is the base common active core of the FGFR ectodomain and that flanking structural domains modify FGF affinity and determine specificity.

Amino Acid Sequence↗
PubMed1999

Marked regional heterogeneity in venous oxygen saturation in severe head injury studied by superselective intracranial venous sampling: case report.

OBJECTIVE: Continuous monitoring of jugular venous oxygen saturation (SjvO2) is useful in the management of severe head injury. Abnormally high SjvO2 values can be caused by increased cerebral blood flow, decreased cerebral metabolism, brain death, contamination from extracerebral venous blood, or traumatic arteriovenous fistula. CLINICAL PRESENTATION: A 20-year-old man with severe head injury was diagnosed to have a traumatic dural carotid-cavernous sinus fistula on the day of trauma. Continuous left SjvO2 monitoring from Days 4 to 12 revealed oxygen saturation ranging between 85 and 98%. INTERVENTION: Superselective intracranial and extracranial venous sampling on Day 5 demonstrated marked regional heterogeneity in venous oxygen saturation as follows: superior sagittal sinus, 95 to 97%; straight sinus, 88%; right transverse sinus, 94%; left transverse sinus, 74%; right SjvO2, 95%; left SjvO2, 89%; the basilar plexus, 99%; right internal jugular vein, 98%; the left internal jugular vein, 94%. Extremely high oxygen saturation in the superior sagittal sinus and basilar plexus was attributed to severe brain damage and carotid-cavernous sinus fistula, respectively. CONCLUSION: Although jugular bulb oximetry is useful in the management of severe head injury, high oxygen saturation values should be interpreted with caution because they cannot show the intracranial heterogeneity of venous oxygen saturation.

Adult↗
PubMed1999

Androgen-stimulated human prostate epithelial growth mediated by stromal-derived fibroblast growth factor-10.

It has been suggested that prostate homeostasis is regulated indirectly by androgens through stromal-epithelial interactions in part by factors from the stromal cells acting on receptors in epithelial cells. In this report, the role of fibroblast growth factor (FGF)-10 in prostatic epithelial proliferation was investigated. The expression of FGF-10 mRNA was apparent in primary-cultured stromal cells, but not in epithelial cells derived from human tissue from patients with benign prostatic hyperplasia (BPH). The mitogenic activity of human recombinant FGF-10 assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation was demonstrated in isolated epithelial cells, but not in cultured stromal cells. No mitogenic activity of dihydrotestosterone (DHT) for either epithelial or stromal cells could be demonstrated, but quantitative PCR (real-time PCR) with a double-labeled fluorogenic probe demonstrated that expression of FGF-10 in stromal cells was enhanced 5.3-fold at a DHT concentration of 100 pM. Androgen receptor mRNA levels showed no significant change with DHT at concentrations less than 100 pM, but were reduced to 50% of control levels at a DHT concentration of 10 nM. These results suggest that stromal-derived FGF-10 stimulates human prostatic epithelial growth and its mRNA expression is induced by androgens, without an increase in the androgen receptor mRNA. Moreover, FGF-10 may be involved in the development or support of human BPH.

Androgens↗
PubMed1998

The glycine box: a determinant of specificity for fibroblast growth factor.

Acidic fibroblast growth factor (FGF-1), keratinocyte growth factor (FGF-7), and FGF-10 are homologues with distinct specificity. In the presence of heparin, FGF-1 binds and activates in vitro all FGFR subtypes, while FGF-7 exhibits absolute specificity for the IIIb splice variant of FGFR2. FGF-10 exhibits a similar specificity but also binds the FGFR1IIIb isoform. Neither FGF-7 nor FGF-10 will bind to IIIc isoforms of FGFR. Molecular models of FGF, heparin, and the FGFR ectodomain suggested that sequences between beta-strands 10 and 12 of FGF may be important for the interaction of FGF with the heparin-FGFR ectodomain duplex. Site-directed mutants of FGF-7 and FGF-10 were prepared to test whether this domain might underlie failure of FGF-7 and FGF-10 to bind to the FGFRIIIc isoforms. Constructions with substitution of FGF-1 sequences spanning the entire C-terminus encoded in exon 3 or only C-terminal sequences spanning beta-strands 10 through 12 conferred ability on FGF-7 to bind to and activate FGFRIIIc without a significant loss in binding to or activation of FGFR2IIIb. A series of twelve different substitutions of shorter segments of FGF-1 sequences into the C-terminal portion of FGF-7 or FGF-10 revealed that substitution of GSCKRG for GIPVRG or the tri-peptide sequence KKN for NQK just N-terminal to it conferred dual activities on both the FGF-7 and FGF-10 backbones. The results suggest that the combined sequence domain, which we call the FGF glycine box (G-box), is a major determinant for the specificity of the binding of FGF to heparan sulfate-FGFR duplexes.

Amino Acid Sequence↗
PubMed1998

Inhibition of growth of malignant rat prostate tumor cells by restoration of fibroblast growth factor receptor 2.

A loss of expression of fibroblast growth factor (FGF) receptor 2 IIIb (FGFR2IIIb), which responds to stroma-derived FGF, accompanies progression of premalignant androgen-responsive rat prostate tumor epithelial cells to the malignant phenotype. Concurrently, the level of FGFR2 gene expression is reduced and lost altogether in over 30% of cells, whereas all malignant cells abnormally express FGFR1, which is normally confined to stromal cells (S. Feng et al., Cancer Res., 57:5369-5378, 1997). To determine the relative roles of the FGFR2 and FGFR1 kinases in growth of malignant cells, we transfected malignant prostate epithelial cells with the wild-type FGFR2IIIb kinase and an artificial chimeric construct (FGFR2IIIb/R1) composed of the FGFR2IIIb ectodomain and the FGFR1 kinase domain. Population growth kinetics, in both the absence and presence of FGF-7, which binds only the FGFR2IIIb ectodomain, were then examined in the transfected cell populations. In contrast to the untransfected malignant tumor cells and those expressing the FGFR2IIIb/R1 chimera, FGF-7 caused a dose-dependent net inhibition of the population growth rates of cells expressing the full-length FGFR2IIIb kinase. The results suggest that although the FGFR2 kinase can mediate positive mitogenic effects, it mediates a net restriction on the growth of prostate tumor epithelial cells relative to FGFR1. Highly malignant prostate tumor cells, which have lost the FGFR2 tyrosine kinase, retain the cellular response mechanisms to it. Restoration of the FGFR2 kinase to malignant tumors that are refractory to treatment may present a new avenue for gene therapy.

Animals↗
PubMed1998

Ligand-dependent and -independent interactions with the transforming growth factor type II and I receptor subunits reside in the aminoterminal portion of the ectodomain of the type III subunit.

The type III receptor for transforming growth factor beta (TGFbeta), which exhibits no kinase activity, binds TGFbeta1 and TGFbeta2 and is involved in assembly and activity of the multi-subunit TGFbeta signal transduction complex. Recently we showed that TGFbeta receptor type III (TbetaRIII) can participate in a complex composed of the dimeric TGFbeta ligand and a type III, II, and I receptor subunit. The interaction of the TbetaRIII subunit with TbetaRII is TGFbeta-dependent, whereas interaction with TbetaRI is TGFbeta-independent. Here we use coexpression of the three types of TGFbeta receptors in baculoviral-infected insect cells to determine which parts of the unglycosylated TbetaRIII receptor participate in the binding of TGFbeta, the TGFbeta-dependent interaction with TbetaRII and the TGFbeta-independent interaction with TbetaRI. The results suggest that the first 500 amino acid residues in the aminoterminal portion of TbetaRIII exhibit all three properties.

Activin Receptors, Type I↗
PubMed1998

The heparan sulfate-fibroblast growth factor family: diversity of structure and function.

The fibroblast growth factor (FGF) receptor complex is a ubiquitous regulator of development and adult tissue homeostasis that bridges the peri-cellular matrix and the intracellular environment. Diverse members of the FGF polypeptide family, the FGF receptor tyrosine kinase (FGFRTK) family and the FGF receptor heparan sulfate proteoglycan (FGFRHS) family combine to result in active and specific FGFR signal transduction complexes. Regulated alternate splicing and combination of variant subdomains give rise to diversity of FGFRTK monomers. Divalent cations cooperate with the FGFRHS to conformationally restrict FGFRTK trans-phosphorylation, which causes depression of kinase activity and facilitates appropriate activation of the FGFR complex by FGF. Diffusional and conformational molecular models of the oligomeric FGFR complex are presented to explain how different point mutations in the FGFRTK commonly cause craniofacial and skeletal abnormalities of graded severity by graded increases in FGF-independent activity of total FGFR complexes. The role of the FGF family in liver growth and function and in prostate tumor progression is discussed.

Adult↗
PubMed1998

Differential expression of transforming growth factor-beta and its receptors in hepatocytes and nonparenchymal cells of rat liver after CCl4 administration.

BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) is a family of multifunctional proteins that regulate hepatocyte proliferation, and biosynthesis of the extracellular matrix. In this study we examined whether modulation of TGF-beta receptor expression contributes to the liver diseases. METHODS: The mRNA expression of TGF-beta1, TGF-beta type I receptor (TGFbetaRI), TGF-beta type II receptor (TGFbetaRII) and TGF-beta type III receptor (TGFbetaRIII) in rat livers injured by CCl4 administration was studied by Northern blotting. The mRNA expression patterns were confirmed by in situ hybridization. RESULT: The peak of TGF-beta1 mRNA expression was observed 48 h after acute intoxication with CCl4 in nonparenchymal cells. However, the levels of TGFbetaRI and TGFbetaRII mRNA expression decreased from 24 h to 48 h and from 12 h to 48 h, respectively, and returned to the normal level by 72 h. TGFbetaRII mRNA expression was depressed more and for longer than that of TGFbetaRI mRNA. Analysis in separated hepatocytes and nonparenchymal cells from the injured livers indicated that the mRNA changes occurred in hepatocytes. Nonparenchymal cells expressed TGFbetaRI and TGFbetaRII mRNAs at constant levels during liver regeneration. TGFbetaRIII mRNA, which also decreased after 12 h, was not apparent in hepatocytes but only in nonparenchymal cells. CONCLUSIONS: These observations suggest that: (i) whenever TGF-beta1 is increased in CCl4-treated livers, it may induce liver fibrogenesis via nonparenchymal cells; (ii) the mitoinhibitory effect of TGF-beta1 on hepatocytes is transiently relieved by down-regulation of TGF-beta receptors for 72 h post-damage; and (iii) the resistance to TGF-beta growth inhibition between 24 to 48 h may be predominantly due to down-regulation of the expression of TGFbetaRII.

Animals↗
PubMed1998

Endovascular treatment of intractable oronasal bleeding associated with severe craniofacial injury.

BACKGROUND: Severe craniofacial injury may cause intractable oronasal bleeding, which is refractory to conventional treatments. This study will evaluate the efficacy of endovascular treatment for such oronasal bleeding. METHODS: Nine males between the ages of 19 and 62 years who had intractable oronasal bleeding resulting from severe craniofacial injuries received treatments of transarterial embolization using Gelfoam pledgets, polyvinyl alcohol particles, or platinum coils. We then reviewed their clinical and neuroradiologic characteristics retrospectively. RESULTS: In all but one case, angiography demonstrated bleeding points as extravasation. These bleeding points were multiple in seven cases. Except for bleeding from ethmoidal arteries, selective embolization was successful. In all cases, intractable oronasal bleeding was controlled. Patient survival was not directly related to oronasal bleeding, but rather was strongly correlated with associated brain injuries. CONCLUSION: Endovascular treatment is an acceptable treatment for intractable oronasal bleeding associated with severe craniofacial injuries when conventional treatments have failed.

Adult↗
PubMed1998

[A case of Salmonella subdural empyema developed in chronic subdural hematoma].

A case of Salmonella subdural empyema developed in chronic subdural hematoma (Infected Subdural Hematoma; ISH) was reported. A 64-year-old man had been in a nearby hospital due to myelodysplastic syndrome with cerebral infarction for two months. His condition there had been almost uneventful. But spike fever occurred and the patient became drowsy two days before his transfer to our medical center. His consciousness level deteriorated progressively and CT scan showed a right chronic subdural hematoma. He had had no history of head trauma in the previous two months. On admission to our center, his consciousness level was semicoma with anisocoria. An emergency operation was performed via a single burr hole initially. From the burr hole, old bloody fluid accompanied by yellowish pus was obtained. Thus so-called ISH was diagnosed and the craniotomy was carried out. Gram stain of the specimen revealed gram negative rods. Although an epileptic state developed after the operation, it was controlled by barbiturate coma therapy for 3 days, followed by phenytoin administration. Fever subsided gradually with antibiotics sensitive to the bacteria and his anisocoria disappeared on the 4th postoperative day. In this case, Salmonella enteritidis was detected from bacterial culture both of the specimen and of the arterial blood. Salmonella enteritidis might have been implanted on the capsule of the chronic subdural hematoma by bacteremia derived from immunological dysfunction due to myelodysplastic syndrome. In conclusion, the possibility of ISH should be considered in chronic subdural hematoma patients with immunological dysfunction.

Chronic Disease↗
PubMed1998

Traumatic carotid cavernous sinus fistula: serial angiographic studies from the day of trauma.

BACKGROUND AND PURPOSE: The purpose of this study was to ascertain the early angiographic features characteristic of traumatic carotid cavernous sinus fistulas (CCFs). METHODS: Eight patients with severe craniofacial injuries underwent emergency diagnostic and therapeutic angiography for intractable oronasal bleeding, starting on an average of 6.7 hours after trauma. Carotid angiograms and the clinical manifestation of traumatic CCFs were then reviewed retrospectively to determine characteristic angiographic features. RESULTS: In four of the eight patients, no arteriovenous fistulas were found in the cavernous sinuses and symptomatic CCF did not occur during the follow-up period. In the remaining four patients, dural CCFs (Barrow type B) were observed, unilaterally in three patients and bilaterally in one. One of these four patients subsequently became symptomatic and required transarterial coil embolization. CONCLUSION: Traumatic dural CCFs are frequently observed in the early stage of severe craniofacial trauma, if investigated. Although their spontaneous disappearance is known, some of these do become symptomatic and need treatment.

Adult↗
PubMed1998

[Application of ultrafast 3D-CT in cervical spine injury].

The authors investigated the usefulness of the ultrafast three-dimensional computed tomography (UF-3D-CT) in cervical spine injury. At Osaka City General Hospital, between April 1995 and March 1998, the authors examined 38 patients with cervical spine injury using UF-3D-CT. The ultrafast CT reduces scanning time. There were no complications associated with the examination. We examined 12 patients with vertebral body fracture, 11 patients with lamina fracture, 8 cases with subluxation including locking facet, 2 patients with atlanto-axial dislocation and 8 patients without bony abnormality. Results suggested that UF-3D-CT was very useful for helping us to understand the bony deformity and the relationship between the bone and the important vessels. UF-3D-CT is very useful for preoperative evaluation and pathophysiological evaluation in cervical spin injury.

Adolescent↗