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Biomedical subjects

M Furukawa

Publications and source records attributed to M Furukawa.

At least 145 records · Page 8Linked to original sources
PubMed1997

Intracerebral penetration of carteolol hydrochloride in rats.

To elucidate the penetrability of carteolol, a beta-adrenoceptor antagonist (beta-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 microgram/g at 2 h postdosing and declined with a half-life of 3.7 h, and the Cmax and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059-0.091 microgram/g and 0.321-0.443 microgram/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6-0.8 h and 1.3-1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability.

Administration, Oral↗
PubMed1997

Restoration of the mucociliary clearance of the maxillary sinus after endoscopic sinus surgery.

BACKGROUND: Whether endoscopic sinus surgery (ESS) restores the mucociliary clearance of the maxillary sinus needs further evaluation. METHODS: We evaluated the mucociliary clearance of the maxillary sinus by using a radionuclide technique in 12 patients with chronic sinusitis (sinusitis group) and in six patients who had undergone ESS 6 to 14 months after the surgery (post-ESS group). The mucosal cilia taken from the maxillary sinus in 12 patients with sinusitis before and after ESS (paired experiments) were examined by light and electron microscopy. RESULTS: The radionuclide placed endoscopically in the maxillary sinus in eight patients immediately after ESS maintained 81.2 +/- 16.3% of its radioactivity after 30 minutes. This result was consistent with results in four patients with untreated chronic sinusitis in whom the radionuclide had been instilled by antral puncture (86.9% +/- 3.5%). On the other hand, in six patients in the post-ESS group the radionucleotide maintained only 25.9% +/- 11.6% of its radioactivity, demonstrating statistically significant differences from those of both the sinusitis group without ESS (p < 0.005) and the group 4 days after ESS (p < 0.005). The absence of the cilia in the sinusitis condition was recognized in 35.5% +/- 12.1% (n = 12) of the epithelial cells. On the other hand, the absence of cilia was significantly (p < 0.01) reduced to 5.3% +/- 3.7% of the epithelial cells in the post-ESS condition. Electron microscopic observation also revealed abnormal cilia in the sinusitis condition, whereas the mucosal cilia were regularly arranged in the post-ESS condition. CONCLUSIONS: The mucociliary clearance of the maxillary sinus disturbed by chronic inflammation was restored by ESS, indicating the clinical effectiveness of ESS for the treatment of chronic sinusitis.

Adolescent↗
PubMed1997

Expression of voltage-dependent chloride channels in the rat cochlea.

Voltage-dependent chloride (ClC) channels have not yet been identified in the cochlea. In this study, an approach utilizing the reverse transcription-polymerase chain reaction (RT-PCR) was devised to clone the cDNA of ClC channels. PCR was performed using degenerate primers corresponding to two highly conserved regions of the ClC channels. By Southern hybridization and sequencing studies, the sequences corresponding to ClC-2 and ClC-3 were found in the cochlear lateral wall, while ClC-1 was not detected. These results suggest that ClC-2 and ClC-3 might be involved in Cl- transport in the cochlear lateral wall.

Animals↗
PubMed1997

Quantitative uronic acid analysis of the otoconial membrane of the guinea pig.

Histochemical and biochemical studies have shown that the otoconial membrane, as well as the tectorial membrane and the cupula, contains glycoproteins and proteoglycans. However, uronic acids, which are essential elements of glycosaminoglycans (GAGs), have not so far been directly detected or quantitatively measured in inner ear samples. In the present study, we quantitatively analyzed the glucuronic acid (GlcA) content of the otoconial membrane of the guinea pig by methanolysis combined with reversed-phase high-performance liquid chromatography (RP-HPLC). The utricular otoconial membrane was treated with thermolysin to separate the supernatant (OM-sup; gelatinous layer) and precipitate (OM-ppt; otoconia). The samples were then subjected to methanolysis followed by brief TFA hydrolysis, incubated with 1-phenyl-3-methyl-5-pyrazolone for labeling, and then analyzed by RP-HPLC coupled with the detection of UV absorbance at 245 nm. The GlcA contents of OM-sup and OM-ppt were 2.1 and 5.8 pmol/100 ng protein, respectively. Based on this result, GlcA-containing GAGs estimated as (GlcA+monosulfo-N-acetylhexosamine)n would be 1.0% of protein in OM-sup and 2.61% of protein in OM-ppt, indicating that this type of glycoconjugate is a minor component in both fractions. It is, accordingly, presumed that both the gelatinous layer and otoconia of the otoconial membrane have totally different properties from those of the tectorial membrane and cartilaginous matrix, which contain abundant GAGs.

Animals↗
PubMed1997

Analysis of DNA ploidy using fresh frozen tissues of head and neck squamous cell carcinomas.

The DNA ploidy of fresh frozen tissues of head and neck squamous cell carcinomas was determined by flow cytometry to investigate whether DNA ploidy is correlated with various clinical and pathological parameters. The subjects were 51 patients who had been treated radically by our department. The DNA ploidy pattern was classified into three types, diploid, single aneuploid and multiploid, according to the DNA index and the DNA histogram. This is our original classification. No particular correlation could be detected between the DNA ploidy pattern and sex, age, primary tumour site or disease stage. The degree of tissue differentiation tended to be poorer in aneuploid tissues than in diploid tissues. The efficacy of chemotherapy was higher in aneuploid cases than in diploid cases. The recurrence rate was significantly lower in diploid cases than in multiploid cases. When disease stage, degree of histological differentiation, efficacy of the chemotherapy and the DNA ploidy pattern were subjected to multivariate analysis for correlation with the prognosis, the DNA ploidy pattern showed the highest correlation. The results suggest that the DNA ploidy as analyzed by flow cytometry can be used as an important prognostic factor.

Aged↗
PubMed1997

Patient with primary tonsillar and gastric syphilis.

A male patient with syphilitic lesions in the tonsil and stomach is presented. The patient was infected while practising oral sex with heterosexual friends. He complained of nausea and snoring; his left tonsil was enlarged. Spirochetes were detected in a smear preparation from the left tonsil. As a gastric lesion, initially believed to be cancer, appeared to result from spirochete ingestion, the case is considered to represent primary syphilis. After antibiotic therapy with ampicillin, the left tonsil returned to normal size and gastric changes were no longer evident endoscopically. Gastroscopy should be considered if syphilis of the tonsil is observed, particularly when gastrointestinal symptoms are present. Both the oral and the gastric lesion can be mistaken for malignant neoplasm.

Adult↗
PubMed1997

Olfactory evoked potential produced by electrical stimulation of the human olfactory mucosa.

Most physiological studies of the human olfactory system have concentrated on the cortical level; the olfactory bulbar level has been studied rarely. We attempted to stimulate the human olfactory mucosa by electrical pulse to detect the bulbar potentials. Electrical stimulation (2 mA, 0.5 ms) of the human olfactory mucosa evoked a change in potential recorded from the frontal sector of the head. A negative peak of the evoked potential that occurred at 19.4 ms (grand means, n = 5) after stimulation was the clearest. The highest amplitude of the potential was recorded from the frontal sector of the head on the stimulated side. Our findings were similar to the experimental results obtained from the olfactory bulbs of animals. This evoked potential was considered to be the human olfactory bulbar potential. When the subjects were stimulated by applying electricity to the olfactory mucosa, no sensation of smell occurred even though evoked potentials were recorded. Evoked potentials were recorded only when the stimulating electrode was located in the olfactory cleft. When the stimulating electrode was outside the olfactory cleft, the stimulation caused pain. The trigeminal nerve seemed to be stimulated by electricity. Olfactory evoked potentials produced by the electrical stimulation of the human olfactory mucosa should aid the research on human olfactory physiology, and may be applicable to clinical tests of olfactory dysfunction.

Electric Stimulation↗
PubMed1997

Clinicopathologic features of resected primary adenosquamous carcinomas of the liver.

Four cases of resected adenosquamous carcinoma of the liver were clinicopathologically reviewed, together with immunohistochemical findings. Although no lymph node metastases were seen and a curative resection was achieved in all cases, two patients had recurrences in the peritoneum and distant organs such as the pericardium and pleura relatively soon after the operation. Of the remaining two cases, one patient died during the postoperative period and the other died of coexistent hilar cholangiocarcinoma. Together these findings suggest that this disease tends to spread locally and distantly in the early phase of tumor growth and shows aggressive biological behavior. In an immunohistochemical study, involucrin was a specific marker for the squamous component and CA19-9 was a marker for the adenomatous component.

Aged↗
PubMed1997

Detection of Epstein-Barr virus in nasopharyngeal carcinoma by in situ hybridization and polymerase chain reaction.

The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) has been shown by various methods. The purpose of this study is to identify the most useful method to detect EBV in NPC. Both polymerase chain reaction (PCR) for EBV-DNA and in situ hybridization for EBV-encoded small RNAs (EBERs) were examined in formalin-fixed, paraffin-embedded NPC specimens. In situ hybridization was performed in 56 cases, and PCR for EBV-DNA was performed in 42 cases. EBV-DNA was detected in 0 of 3 keratinizing squamous cell carcinomas (KSCC), 22 of 24 nonkeratinizing carcinomas (NKC), all 13 undifferentiated carcinomas (UNPC), and 0 of 2 adenocarcinomas (AC). EBERs were detected in 0 of 5 KSCC, 30 of 32 NKC, 16 of 17 UNPC, and 0 of 2 AC. Among them, EBERs was detected in 35 of 42 cases in which PCR was also performed, 0 of 3 KSCC, 22 of 24 NKC, all 13 UNPC, and 0 of 2 AC, respectively. Both results were consistent in 40 of 42 cases. We conclude that both PCR and in situ hybridization are useful to detect EBV in NPC. In situ hybridization has a particular advantage because it can demonstrate the localization of EBV in neoplastic cells. In addition, close association of NKC and UNPC but not KSCC and AC with EBV is suggested.

Adenocarcinoma↗
PubMed1997

Expression of adhesion molecules in nonallergic chronic sinusitis.

Endothelial and epithelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. To determine the relationship between recruited leukocytes and adhesion molecules in the paranasal sinus mucosa of nonallergic chronic sinusitis, we surgically obtained mucosa from 16 patients and identified the expression of intercellular adhesion molecules (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin by immunohistochemistry. Neutrophils were significantly dominant in the nasal discharge as compared with eosinophils. The degree of neutrophil infiltration in the paranasal sinus mucosa was prominent in both intraepithelial and subepithelial areas as compared with the lamina propria. In each tissue site, the degree of infiltration of neutrophils was similar to that of eosinophils. These findings suggest that the tissue neutrophils actively and rapidly migrated into the lumen. All the adhesion molecules except VCAM-1 were expressed in the vascular endothelial cells. On the other hand, the surface epithelial cells showed the expression of only ICAM-1. The expression of ICAM-1 on the endothelial cells correlated with the degree of neutrophil infiltration in the mucosa The eosinophil infiltration was not dependent on any adhesion molecules examined here. It was concluded that ICAM-1 expression in the mucosa may be involved in neutrophil recruitment and may contribute to the establishment of the inflammatory cell distribution in the paranasal sinus of nonallergic chronic sinusitis.

Adolescent↗
PubMed1997

Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells.

The mechanism of macrolide therapy in chronic sinusitis patients is unclear. The authors studied the effect of macrolides on interleukin (IL)-8 secretion from cultured human nasal epithelial cells. Epithelial cells harvested from the nasal polyps of patients with chronic sinusitis were primary-cultured, and secreted IL-8 in culture media was measured by enzyme immunoassay. The cells secreted considerable amounts of IL-8 constitutively and in response to lipopolysaccharide. The secretion was significantly inhibited by 10(-5) M of erythromycin, clarithromycin, roxithromycin, and josamycin. 10(-6) M erythromycin still showed the inhibitory effect, whereas the same concentration of josamycin did not. These results indicate that macrolide antibiotics may act as an immunomodulator to reduce IL-8 in inflammatory sites and, at least partially, account for the clinically discrepant effects between 14- and 16-membered ring macrolides in long-term low-dose therapy for chronic sinusitis.

Adult↗
PubMed1997

Langerhans cell histiocytosis (histiocytosis X) with morphologic expression of desmosomes and microvillous structures.

An unusual case of Langerhans cell histiocytosis in a 7-year-old female is presented. She had ultrastructural evidence of desmosomal biogenesis and formation of gland-like structures by lesional cells; their apical plasma membranes were folded into large numbers of microvilli. Despite the presence of these structures characteristic of epithelial cells, an infiltrated plaque on the abdominal skin of this patient was interpreted as cutaneous involvement of multiple system Langerhans cell histiocytosis because the immunohistochemical staining of the lesional cells for CD1a, S100, PNA, CD4, EN-4, and HLA-DR was positive, and numerous Birbeck granules were ultrastructurally identified in some lesional cells. Other clinical data included the presence of scaly erythematous skin lesions on the forehead and lytic osseous lesions in the maxilla, which were also histologically diagnosed as Langerhans cell histiocytosis. The absence of any internal malignancy in this patient readily ruled out the other diagnostic possibility of a metastatic adenocarcinoma showing glandular differentiation with brush border morphogenesis. The possibility that the desmosome-linked lesional epithelioid cells were actually cells of sweat glands entrapped in the histiocytic proliferation was also ruled out. The functional significance of the desmosomes and microvillous structures in the present case of Langerhans cell histiocytosis remains to be clarified. Awareness of this variant of Langerhans cell histiocytosis will be important for averting potential misdiagnosis in favor of epithelial tumors, especially metastatic adenocarcinomas.

Child↗
PubMed1997

Effects of extracellular ATP on ion transport and [Ca2+]i in Mongolian gerbil middle ear epithelium.

The present study investigates the effects of ATP on ion transport and Ca2+ mobilization in primary cultures of gerbil middle ear epithelium. Extracellular ATP and other nucleotides elicited a transient increase in short-circuit current (I(sc)) in a dose-dependent manner. The rank order of potency in I(sc) responses corresponded with the sequence of the P(2u) purinergic receptor when applied to the mucosal or the basolateral side. Extracellular ATP induced a rise in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. A similar rank order of potency in the ATP-induced increases in [Ca2+]i was observed. The time courses of the [Ca2+]i responses induced by ATP closely paralleled those of the I(sc) responses. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester greatly reduced the increase in the I(sc) and [Ca2+]i responses to ATP. Diphenylamine-2-carboxylate, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, quinidine, and Ba2+ significantly blocked the ATP-stimulated I(sc). Glibenclamide had no effect on the ATP-stimulated I(sc). These results are consistent with the hypothesis that extracellular ATP and other nucleotides induce Cl- secretion across the apical membrane in cultured gerbil middle ear epithelium by activation of the apical Cl- channels via multiple modes of regulation.

Adenosine Triphosphate↗
PubMed1997

P2 purinoceptor of the globular substance in the otoconial membrane of the guinea pig inner ear.

The biological characteristics of the globular substance, a precursor of otoconia, are unclear. In the present study, the ATP-induced internal free Ca2+ concentration ([Ca2+]i) changes of the globular substance and the ATP distribution in the vestibular organ were investigated using a Ca2+ indicator, fluo 3, and an adenine nucleotide-specific fluorochrome, quinacrine, by means of confocal laser scanning microscopy. [Ca2+]i showed a rapid and dose-dependent increase in response to ATP with a 50% effective concentration (EC50) of 16.7 microM. This reaction was independent of external Ca2+, indicating the presence of an internal Ca2+ reservoir. Neither adenosine, alpha, beta-methylene-ATP, 3'-O-(4-benzoylbenzoyl)-ATP, ADP, nor UTP evoked this reaction, whereas 2-methylthio-ATP induced an increase of [Ca2+]i with an EC50 of 14.4 microM. Moreover, P2 antagonists, reactive blue 2 and suramin, and a phospholipase C inhibitor, U-73122, inhibited the ATP-induced [Ca2+]i increase. These findings indicate the presence of a P2Y purinoceptor on the globular substance. In addition, granular fluorescence was observed in the quinacrine-stained macular sensory epithelium, indicating the presence of ATP-containing granules in this tissue. These results suggest that a paracrine mechanism involving ATP may exist in the macula and that this mechanism regulates the biological behavior of the globular substance.

Adenosine Diphosphate↗
PubMed1997

Lysozyme loading and release from hydrogels carrying pendant phosphate groups.

To develop a polymeric matrix for efficiently loading cationic biomolecules, polyelectrolyte hydrogels carrying pendant phosphate groups were synthesized by copolymerizing 2-methacryloyloxyethyl dihydrogen phosphate with N-isopropylacrylamide and N, N1-methylene-bis-acrylamide. The phosphate-carrying monomer yielded anionic hydrogels, which formed ionic complexes with the cationic protein, lysozyme. It was shown that the amount of complexed lysozyme reached 2.1 g g-1 dry gel, corresponding to 1.3 x 10(-3) mol phosphate group per gram lysozyme, when 40 mol% of phosphate-carrying monomer was incorporated in a hydrogel. When the hydrogel complexed with lysozyme was placed in deionized water and various KCl solutions, of varying concentrations of up to 0.5 M KCl, no lysozyme was released in deionized water, while increasing amounts of lysozyme were released as the KCl concentration increased. This confirmed that lysozyme was loaded in the hydrogel through electrostatic interactions. It was further found that the complexed lysozyme retained its enzymatic activity after being released from the hydrogel. These results suggest the use of this system for the controlled release of cationic protein drugs.

Biocompatible Materials↗
PubMed1997

Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.

Adult↗
PubMed1997

Pharmacological profiles of a new antiulcer agent, SWR-215.

We investigated the effects of a new antiulcer agent, SWR-215 ([[(1,2-dihydro-2-oxo-4-quinolinyl)methyl]thio]-N-[[[4-(1-piperidinyl methyl)-2-pyridinyl]oxy]-Z-2-butenyl]acetamide), on histamine H2-receptors, gastric acid secretion and various acute experimental gastric lesions. SWR-215 showed unsurmountable histamine H2-antagonism on isolated guinea-pig atrium. In gastric secretion studies, SWR-215 exhibited potent and durable inhibitory effects, and the antisecretory activities were much stronger than that of roxatidine acetate hydrochloride (roxatidine): 5 times stronger on basal acid secretion in pylorus ligated rats, 11 times stronger on histamine-stimulated acid secretion in acute fistula rats, and 2 times stronger on histamine stimulated acid secretion in Heidenhain-pouch dogs, respectively. In various experimental acute gastric lesion studies, SWR-215 potentially inhibited almost all acute gastric and duodenal lesions compared with roxatidine, especially indomethacin-induced and HCl-ethanol-induced gastric lesions, and the inhibitory effects were exhibited at the same or lower doses than those which caused the antisecretory effect. Furthermore, it was considered that the mucosal protective effect of SWR-215 was probably unrelated to the endogenous prostaglandin system in gastric mucosa. These results suggest that SWR-215 possesses both durable antisecretory and mucosal protective effects, and is expected to be a useful drug for the treatment of patients with peptic ulcers.

Animals↗