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Biomedical subjects

A Morikawa

Publications and source records attributed to A Morikawa.

At least 19 recordsLinked to original sources

Small adenocarcinoma of the lung. Histologic characteristics and prognosis.

BACKGROUND: Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. METHOD: Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. RESULTS: Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. CONCLUSION: Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis.

Adenocarcinoma

Rapid gastric emptying and pathological changes of vagus nerve in the spontaneously diabetic Chinese hamster.

To estimate autonomic neuropathy in the spontaneously diabetic Chinese hamster, which is an established strain for the non-obese non-insulin-dependent diabetes mellitus model, gastric emptying and morphometric analysis of the vagus nerve were studied in 12-month-old spontaneously diabetic Chinese hamsters (duration of diabetes was 9 months). Gastric emptying was determined by the phenol red method. Vagus was obtained from just above the diaphragm. Morphometric analysis of myelinated fibers was performed light-microscopically using semi-thin sections and unmyelinated fibers were studied electron-microscopically using ultra-thin sections. Gastric emptying of spontaneously diabetic Chinese hamster was significantly increased compared with control (86.6 +/- 1.9 vs. 51.2 +/- 3.4, P < 0.01). Myelinated fibers of the spontaneously diabetic Chinese hamster were not different from control animals, while the size of unmyelinated fibers in the spontaneously diabetic Chinese hamster was significantly decreased. These data suggest that pathological changes in unmyelinated fibers, which consist mainly of afferent fibers, might play a role in gastric motor dysfunction in the spontaneously diabetic Chinese hamster.

Animals

Relationship between ultrasonically nebulized distilled water-induced bronchoconstriction and acetic acid-induced cough in asthmatic children.

BACKGROUND: Although wheezing and cough are the most common complaints in asthmatic persons, the mechanisms of hyperresponsiveness to bronchoconstriction and cough are nevertheless still unclear. OBJECTIVE: To investigate the common mechanisms between them, we studied the relationship between ultrasonically nebulized distilled water (UNDW) inhalation challenge and acetic acid (AA) inhalation challenge. In addition, we evaluated the effect of inhaled furosemide on both provocation tests by means of a placebo-controlled study. METHOD: In study 1 the UNDW, AA, and histamine inhalation challenges were performed in 40 asthmatic children (26 boys, aged from 7 to 16 years; mean +/- SD, 11.2 +/- 2.0 years). In study 2, 12 of the study 1 subjects (9 boys, 11.3 +/- 2.4 years) were subjected to each challenge test after inhalation of furosemide (10 mg/body square meters), or placebo (0.9% saline solution) on separate days. RESULTS: There was a good correlation between the provocative dose causing a 20% fall in forced expiratory volume in 1 second in the UNDW inhalation challenge (UNDW-PD20) and threshold dose causing cough in the AA inhalation challenge (R = 0.527; p < 0.001). There was no relationship either between UNDW-PD20 and the provocative concentration causing a 20% fall in the histamine inhalation challenge (histamine-PC20)(R = 0.384; p > 0.1), or between histamine-PC20 and the cough threshold (R = 0.308; p > 0.05). In study 2 neither bronchoconstriction nor bronchodilation after inhalation of furosemide was observed. Inhaled furosemide exerted a protective effect on UNDW-PD20 and cough threshold of the AA inhalation challenge (p < 0.01 and p < 0.01, respectively), but did not attenuate histamine-PC20 (p > 0.1). CONCLUSION: These data suggest that a common mechanism may cause hyperresponsiveness against both UNDW-induced bronchoconstriction and AA-induced cough in asthmatic children.

Acetates

Ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to attenuate eicosanoid-induced airflow obstruction and airway microvascular leakage.

Beta-2 adrenoceptor agonists are widely used as bronchodilators in the treatment of asthma mainly via inhalation. In the present study, we evaluated the ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to reduce eicosanoid-induced airway microvascular leakage, and compared the ability with its inhibitory effect against bronchoconstriction. Tracheostomized guinea-pigs were given aerosolized procaterol (10 or 100 micrograms/ml) for 10 min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20 mg/kg) was given i.v. One minute later, 2 nmol/kg leukotriene D4 (LTD4), 50 nmol/kg U-46619, a thromboxane A2 mimetic, or vehicle was administered i.v. LTD4- or U-46619-induced increase in lung resistance was measured for 6 min. After removing the lungs, the amount of extravasated Evans Blue due in the lower airways was examined as an index of microvascular leakage. Inhaled procaterol significantly attenuated increases in both lung resistance and Evans Blue dye extravasation caused by these eicosanoids. The degree of inhibition was almost complete for lung resistance (approximately 90%), but it was only partial (range 18.5-61.2%) for the dye extravasation. No significant changes in mean systemic blood pressure and in heart rate was observed after an inhalation of 10 micrograms/ml procaterol. These results suggest that inhaled beta 2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation.

Adrenergic beta-Agonists

Airway responses following intradermal sensitization to different types of allergens: ovalbumin, trimellitic anhydride and Dermatophagoides farinae.

Sensitization of guinea pigs by intradermal injections of the occupational allergen trimellitic anhydride (TMA) in oily vehicle has been shown to be very reproducible. We studied the effect of intradermal sensitization with ovalbumin (OA) in oily vehicle on immune and airway responses in guinea pigs. We also compared airway responses to trimellitic anhydride or Dermatophagoides farinae (DF; mite) with those to OA in guinea pigs intradermally sensitized to respective allergens. Three to four weeks after sensitization, the animals were challenged with intratracheal instillation of these allergens. Intradermal injections with OA developed dose-dependently specific IgG1 antibodies to OA demonstrated by ELISA. In animals sensitized with different doses of OA in corn oil vehicle, a challenge with OA induced a reversely dose-dependent airflow obstruction and airway plasma exudation. In contrast, animals sensitized with OA in saline vehicle had dose-dependent airway responses to OA. Challenge with OA caused an immediate peak and subsequently persistent airflow obstruction, whereas this response to either TMA guinea pig serum albumin or Df was slowly progressive in animals sensitized to respective allergens. The animals sensitized to TMA or Df may show a different profile of airway responses following the challenge compared to OA. Intradermal sensitization may be a valuable method of sensitization for the development of an animal model of airway allergy to different types of allergens, including chemicals or mites.

Allergens

Inhaled indomethacin prevents bronchoconstrictive response to distilled water but not to histamine in children with asthma.

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), against bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten children with asthma (eight males and two females, with a mean +/- SEM age of 10.7 +/- 0.7 yr), who had a decrease in FEV1 of at least 20% after UNDW inhalation, were enrolled in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body-surface area) or placebo (0.9% saline) according to a single-blind, randomized, crossover design, and underwent a UNDW challenge test 15 min after the pretreatment. Furthermore, to study the possibility that indomethacin has a direct effect on airway smooth muscle, bronchial provocation with histamine was performed in seven subjects on two further days after pretreatment with indomethacin or placebo. Inhaled indomethacin had no effect on baseline pulmonary function, but did prevent the UNDW-induced decline in FEV1 (p < 0.01). Inhaled indomethacin did not modify the bronchoconstrictor response to histamine, indicating that a direct effect of this agent on airway smooth muscle is unlikely. The inhibition of local prostaglandin synthesis in the airways may be involved in the effect of indomethacin.

Administration, Inhalation

Syntheses of novel galactosyl ligands for liposomes and the influence of the spacer on accumulation in the rat liver.

We modified the surface of liposomes with galactosyl ligands. At first we determined whether or not the galactosyl moiety was exposed on the liposomes. We then investigated the effect of the ligands on the hepatic accumulation of liposomes in rats. We introduced an oligoethylene glycol moiety as a spacer. Among the various ligands tested, those with a tri- or tetraethylene glycol moiety as a spacer caused the greatest accumulation of liposomes in the liver. Liposomes bearing ligands with a tri- or tetraethylene glycol moiety as a spacer, were aggregated by Ricinus communis agglutinin. On the other hand, those modified with ligands with a mono- or diethylene glycol spacer did not clearly agglutinate. These results show the importance of a spacer between the homing device and the ligand anchor.

Animals

Relationship between the anchor structure of the galactosyl ligand for liposome modification and accumulation in the liver.

Liposomes which have been modified with (8-hexadecanoylamido-3,6-dioxaoctyl)-beta-D-galactose (Gal-t-pa), a straight chain palmitoyl derivative, and are composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH), and dicetyl phosphate (DCP) at a ratio of 10:10:1, showed the same accumulation in the liver as the control liposome. Also, liposomes which have been modified with [8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl]-beta-D-gal actoside (Gal-t-psa) showed remarkable accumulation in the liver. The accumulation of liposomes modified with galactose derivatives in the rat liver differed markedly according to the anchor structure. To clarify the cause of this finding, we produced [3H]inulin entrapped [14C]Gal-t-pa modified double label liposomes and evaluated changes in their rat plasma concentration, distribution in the organs, and the in vitro interaction with rat plasma. [14C]Gal-t-pa on the liposome surface bound to serum albumin and was released, resulting in no accumulation in the liver. In addition, sialic acid palmitoyl derivatives and glucuronic acid palmitoyl derivatives behaved similarly. As with the galactose derivatives, they also bound to serum albumin, being released from liposomes. These results suggest that adequate attention should be paid to the anchor structure of the ligand, in order to incorporate a recognition element into liposomes for transport to cells.

Animals

Inhaled diuretics attenuate acid-induced cough in children with asthma.

To evaluate the effect of inhaled diuretics, furosemide and amiloride, on cough induced by acid inhalation challenge in asthmatic children, a double-blind, randomized, placebo-controlled study was conducted. On separate days, 12 asthmatic children (10.3 +/- 0.7 [SEM] years) underwent acetic acid (AD) inhalation challenge after inhalation of furosemide (10 mg/m2 of body) amiloride (0.3 mg/m2 of body), or placebo (0.9% saline solution). Bronchoconstriction was not observed after administration of furosemide and amiloride. Both inhaled furosemide and amiloride exerted a protective effect against AA-induced cough in asthmatic children (p < 0.01 and p < 0.05, respectively), while there was little correlation between the individual protective potency of furosemide and amiloride against AA-induced cough (rs = 0.344, p = 0.255). These results demonstrate that both furosemide and amiloride can attenuate AA-induced cough, although, this protective effect of inhaled diuretics may not necessarily be dependent on Na(+)-K(+)-Cl- cotransporter or Na+ channel in airway epithelial cells.

Acetates

Effect of procaterol, a beta 2-adrenoceptor agonist, on skin whealing response caused by inflammatory mediators in asthmatic children.

BACKGROUND: Beta 2-adrenoceptor agonists have been shown to reduce allergen-induced skin whealing responses via inhibition of mediator release. OBJECTIVE: To study whether beta 2-adrenoceptor agonists have a direct action against inflammatory mediator-induced skin whealing responses. METHODS: We examined the effect of procaterol, a beta 2-adrenoceptor agonist, on skin whealing responses to histamine, platelet-activating factor (PAF), substance P, or bradykinin in eight asthmatic children in a double-blind, randomized, cross-over study. Two hours after taking procaterol (50 micrograms) or placebo orally, the subjects were given these mediators intradermally at a concentration of 10(-5) M. RESULTS: Procaterol has a small but significant inhibitory effect on wheal formation following the intradermal injection of histamine and PAF by an average of 15% (P < .05) and 18% (P < .05) respectively but not against substance P or bradykinin. CONCLUSIONS: Our results suggest that although beta 2-adrenoceptor agonists may have an inhibitory effect against plasma exudation from microvasculature in the human skin, bronchodilatory effects are more prominent.

Adolescent

Clinical and immunologic surveys of Hymenoptera hypersensitivity in Japanese forestry workers.

BACKGROUND: The increased incidence of bee-sting allergy among beekeepers is well known, whereas Hymenoptera hypersensitivity among forestry workers, who are frequently stung by Hymenoptera, is not well understood. OBJECTIVE: To elucidate the nature of Hymenoptera hypersensitivity among forestry workers and analyze the mechanism involved in Hymenoptera-induced systemic reactions. METHODS: A questionnaire was administered and yellow jacket venom-specific IgE antibody titers measured in 323 forestry workers and 100 age-matched office workers with little occupational exposure to Hymenoptera stings as a control group. RESULTS: From the questionnaire it was found that the percentage of systemic reactions to Hymenoptera stings was significantly greater in the forestry workers than in the control subjects (P < .01). The number of sting exposures was significantly higher in the forestry workers than in the control subjects (P < .01) and was closely correlated with episodes of systemic reaction. Yellow jacket venom-specific IgE antibody titers were significantly higher in forestry workers with episodes of systemic reaction compared with those with only local or large local reactions to Hymenoptera (P < .05), although more than half of these subjects had undetectable IgE antibody titers to yellow jacket venom. IgE antibody titers against yellow jacket venom were closely correlated with those of paper wasp (rs = .802, P < .001), which is another frequent source of Hymenoptera stings. In workers with episodes of sting exposure within the most recent 3 years, the period from the last sting was not correlated with yellow jacket venom-specific IgE antibody titers. CONCLUSIONS: The number of sting exposures may contribute to systemic reactions to Hymenoptera sting, and some mechanism other than IgE mediated hypersensitivity may also be involved in Hymenoptera-induced systemic reactions.

Adult

Effect of inhaled furosemide on lung clearance of technetium-99m-DTPA.

UNLABELLED: The diuretic furosemide has been reported to have a protective effect on allergic asthmatic reactions. This study was performed to investigate the effect of aerosolized furosemide on the lung clearance of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: Pulmonary clearance rates of 99mTc-DTPA were measured by a computerized gamma camera with and without the inhalation of aerosol furosemide in 6 nonsmoking normal volunteers (Group 1), 7 smokers without pulmonary disease (Group 2) and 11 patients with asthma (Group 3). RESULTS: None of the six normal volunteers showed significant effects of inhaled furosemide on the 99mTc-DTPA clearance rates. Three of seven smokers presented an accelerated 99mTc-DTPA clearance by inhaled furosemide and the other four showed no significant change of 99mTc-DTPA clearance by furosemide inhalation. However, in 10 of 11 patients with asthma, there was significant suppression of 99mTc-DTPA clearance by furosemide inhalation. CONCLUSION: Asthmatics possess a furosemide-sensitive mechanism. Pulmonary aerosol scintigraphy with 99mTc-DTPA will be useful in predicting the effect of inhaled furosemide therapy.

Administration, Inhalation

A method for determination of galactosyltransferase I activity synthesizing the proteoglycan linkage region.

An assay method was devised for measuring the activity of galactosyltransferase I (UDP-D-galactose:D-xylose galactosyltransferase), which is one of the enzymes synthesizing the linkage region between the core protein and glycosaminoglycan chains of proteoglycan. For this method, the reaction mixture contained a fluorescent substrate, 4-methylumbelliferyl-beta-D-xyloside as an acceptor, UDP-galactose as a donor and D-galactal as a competitive inhibitor of endogenous beta-galactosidase in the enzyme solution. The reaction mixture was incubated at 37 degrees C with enzyme solution prepared from an extract of cultured cells, and galactosyl-xylosyl-4-methylumbelliferone was produced as a reaction product. Measurement of galactosyltransferase I activity was performed by separation and quantitative analysis of this reaction product using high-performance liquid chromatography. Utilizing this method, easier and more sensitive detection of galactosyltransferase I activity in a cell-free system became possible. Application of the method revealed that cultured human skin fibroblasts contained galactosyltransferase I activity.

Binding, Competitive

Urinary bladder dysfunction in spontaneously diabetic Chinese hamsters.

Urinary bladder dysfunction was investigated in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD). The wet weight of the urinary bladder was significantly increased in CHAD when compared with non-diabetic controls. In response to continuous infusion of physiological saline into the bladder under anesthesia, regular micturition was observed in controls. However, the threshold volume (i.e. the minimum volume at which rhythmic contraction appeared) was significantly increased and the amplitude of bladder contractions during micturition was decreased in CHAD aged 3-5 months (duration of diabetes, 0.6-2.2 months), leading to incomplete micturition. The frequency of micturition was also increased. Overflow incontinence was observed in all CHAD aged 13-15 months (duration of diabetes, 10-14 months). Acetylcholinesterase staining and activity in the urinary bladder walls were both significantly decreased in CHAD compared with controls. The in vitro increment of urinary bladder pressure caused by stimulation with bethanechol was not different between CHAD and controls. These findings suggest that CHAD have urinary bladder dysfunction which is caused by autonomic neuropathy and not by detrusor myopathy.

Acetylcholinesterase

Localization of apoptosis (programmed cell death) in mice by administration of lipopolysaccharide.

Localization of apoptotic cells by administration of lipopolysaccharide into mice was studied by using the in situ specific labeling of fragmented DNA. This method clearly stained the nuclei of thymocytes at the cortex of the thymus. The nuclei of cells in the bone marrow and in the spleen were also positively stained. It was suggested that the cortex in the thymus is where the LPS-induced programmed cell death occurs.

Animals

Effects of cilostazol, a cyclic nucleotide phosphodiesterase III inhibitor, on substance P-induced airflow obstruction and airway microvascular leakage in guinea pigs.

We studied the effect of cilostazol, a cyclic nucleotide phosphodiesterase (PDE) III inhibitor, on a substance P (SP)-induced increase in lung resistance and in airway microvascular leakage in guinea pigs in vivo. Four minutes after intravenous (i.v.) administration of cilostazol (1.5 and 5 mg/kg) or vehicle, Evans blue dye (20 mg/kg) was given i.v. One minute later, 30 nmol/kg SP was administered i.v. The SP-induced increase in lung resistance was measured for 6 min. Following the measurement of lung resistance, microvascular leakage at the trachea, main bronchi and intrapulmonary airways was also examined. Cilostazol attenuated the SP-induced increase in lung resistance, with a significant inhibition at the concentration of 5 mg/kg. Five milligrams per kilogram cilostazol also significantly inhibited SP-induced Evans blue dye extravasation at the trachea and main bronchi. These results suggest that cilostazol might reduce airflow obstruction which is seen in diseases such as asthma through attenuation of bronchoconstriction and, possibly, airway edema resulting from airway microvascular leakage in man.

Airway Obstruction