Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 217 records · Page 12Linked to original sources

PubMed1998

Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion.

Soluble forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been identified in the peripheral blood and other body fluids. These soluble adhesion molecules have been reported to reflect the upregulation of cell surface ICAM-1 and VCAM-1 expression in inflammatory diseases. The levels of soluble ICAM-1 and soluble VCAM-1 in 37 middle ear effusions from 37 patients with chronic otitis media with effusion (OME) were quantitatively determined with enzyme-linked immunosorbent assays. The levels of soluble ICAM-1 in mucoid effusions were significantly higher than those in serous effusions, but the levels of soluble VCAM-1 did not differ significantly between the two types of effusion. The levels of soluble VCAM-1 in effusions from atopic patients were significantly higher than those from non-atopic patients, whereas the levels of soluble ICAM-1 in samples from atopic patients were significantly lower than those from non-atopic patients. Therefore, our data suggest that an increase in soluble VCAM-1 plays a more important role in the pathogenesis of OME in atopic patients than in non-atopic patients. In addition, soluble ICAM-1 is likely to play a more important role in the pathogenesis of OME in nonatopic patients than soluble VCAM-1.

Adult↗

PubMed1998

ClpC regulates the fate of a sporulation initiation sigma factor, sigmaH protein, in Bacillus subtilis at elevated temperatures.

Using a strain carrying a clpC-bgaB transcriptional fusion at the amyE locus, we found that the expression of a clpC operon was induced at the end of exponential growth in a sigmaB-independent manner and ceased around T3.5 in the wild type but not in a spo0H mutant. This suggests that some gene product(s) whose expression is dependent on sigmaH function is required for the turn-off of clpC transcription during an early stage of sporulation. A clpC deletion mutant showed a temperature-sensitive sporulation phenotype and exhibited an abnormally large accumulation of sigmaH in the cell at 45 degrees C after T2, at which time the sigmaH level in the wild type had begun to decrease. These results, together with the fact that spo0H transcription in the clpC deletion mutant was similar to that of the wild type, suggested that ClpC may be responsible for the degradation of sigmaH after the accomplishment of its role in sporulation. Moreover, as expected from these results, overproduction of Spo0A was also observed after the initiation of sporulation in the clpC deletion mutant at 45 degrees C.

Bacillus subtilis↗

PubMed1998

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗

PubMed1998

Allergen-induced synthesis of interleukin-5, but not of IgE, is a key mechanism linked to symptomatic episodes of seasonal allergic rhinitis in sensitized individuals.

Some individuals with detectable levels of Japanese cedar (Criptomeria japonica) pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen allergen might differ fundamentally between asymptomatic and symptomatic individuals who are already sensitized to the pollen. The aim of this study was to discern the possible differences in responses of peripheral blood mononuclear cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic subjects who have been sensitized to the pollen. This study included 20 non-atopic healthy volunteers (non-atopic group) and 48 patients who had detectable levels of the pollen-specific IgE before the pollen season in 1997. In the review of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms of seasonal allergic rhinitis (symptomatic group), and the remainder had no seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual during the pollen season and cultured in the absence or presence of 12.5 microg of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and interferon-gamma (IFN-gamma) in the culture supernatants were measured. The levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and symptomatic groups were significantly higher than those of the non-atopic group, but did not differ between the asymptomatic and symptomatic groups. The levels of IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between the non-atopic group and the asymptomatic group, but the levels of IL-5 were significantly higher in the symptomatic group than in the asymptomatic group as well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1-stimulated PBMCs did not differ significantly among the three groups. In conclusion, our study has suggested that Japanese cedar pollen-induced synthesis of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to the symptomatic episode of seasonal allergic rhinitis in individuals sensitized to the pollen.

Adolescent↗

PubMed1998

Immunotherapy suppresses both Th1 and Th2 responses by allergen stimulation, but suppression of the Th2 response is a more important mechanism related to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

Increased attention has recently been directed at the possibility that the clinical efficacy of immunotherapy might be elaborated by alteration of T-cell reactivity. However, there is no general agreement among different investigators regarding the effect of immunotherapy on Th-cell reactivity. Peripheral blood mononuclear cells (PBMCs) from 15 nonatopic subjects and 76 patients with perennial allergic rhinitis (18 untreated patients and 58 patients on immunotherapy) were cultured in the absence and in the presence of a major Dermatophagoides farinae allergen, Der f 1, and the levels of IgE, interleukin-5 (IL-5), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatants were determined. The difference between the absence and presence of Der f 1 was calculated to consider the Der f 1-dependent synthesis of IgE, IL-5, IFN-gamma and TNF-alpha. The levels of Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha were significantly higher in the untreated group than in the nonatopic group, whereas Der f 1-dependent synthesis of IFN-gamma was significantly lower in the untreated group than in the nonatopic group. Immunotherapy decreased the enhanced Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha, and further decreased the suppressed Der f 1-dependent synthesis of IFN-gamma as the therapy proceeded. The levels of Der f 1-dependent synthesis of IgE and IL-5 did not differ between nonatopic individuals and patients whose duration of immunotherapy was 10 or more years. The levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, were correlated significantly with the levels of symptom scores. In addition, the levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, differed significantly between good and poor responders. In conclusion, immunotherapy for perennial allergic rhinitis may possibly work via induction of tolerance or anergy of both Th1- and Th2 cells. However, our study is likely to support a view that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the tolerance of Th2- rather than Th1 cells. In addition, suppression of IgE synthesis is also likely to be linked to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

Allergens↗

PubMed1998

The safety system for the rotary blood pump, combination of the valve and LVAD pulsatile mode: in vitro test.

The significant amount of regurgitation produced by a stopped rotary blood pump is one of the major considerations for its use as an implantable left ventricular assist device (LVAD), especially if the pump accidentally stops. The installation of a valve is an option for the solution of this potential problem. However, this option may lead to thrombogenic problems, particularly if the valve motion is restricted. This in vitro study analyzes the valve performance and assesses the credibility of a rotary blood pump valve. A pulsatile pump was used as the natural heart and a centrifugal pump as the LVAD. The valve was positioned into the LVAD outflow. In the low speed range (<1,000 rpm in this test condition), normal valve motion was maintained. Also, the valve model provided a higher mean bypass flow than the model without a valve due to reduced regurgitation. However, the valve motion was drastically restricted when in the high speed range (>1,600 rpm in this condition). The pulsatile mode was applied to the LVAD by periodically changing the impeller speed (40 bpm); subsequently, a constant valve motion could be provided. A possibility exists that this pulsatile mode application could eliminate thrombosis formation around the valve. A conclusion was made that the combination of a valve and an LVAD in a pulsatile mode is considered to be a unique safety system for a rotary blood pump.

Blood Pressure↗

PubMed1998

In vivo evaluation of the miniaturized Gyro centrifugal pump as an implantable ventricular assist device.

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 +/- 0.57 L/min, input power of 6.16 +/- 0.49 W, and the inside temperature of the actuator of 43.5 +/- 0.52 degrees C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.

Animals↗

PubMed1998

Estimation of the native cardiac output from a rotary blood pump flow: in vitro study.

The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.

Aorta↗

PubMed1998

Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.

Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients. But it is often impossible to administer enough dose to suppress parathyroid hormone (PTH) level, because of hypercalcemia and hyperphosphatemia. New modalities with higher specificity for PTH suppression are desirable. We conducted a crossover comparative study of falecalcitriol, an active vitamin D3 analog, and alfacalcidol (1alpha[OH]D3). In this study, 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled. They received daily oral doses of alfacalcidol during an 8-week observation period. Based on serum calcium levels and intact PTH, the subjects were allocated into two groups, and a comparative study was conducted using unmasked crossover design of two drugs x two periods. The dosage of both drugs was adjusted to maintain the initial serum calcium levels, and the relative change (%change) of serum biochemical parameters were compared. Comparison of two drugs in period 1 was taken as primary efficacy evaluation. Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2. The percent change of PTH of falecalcitriol was lower than that of alfacalcidol: Those were, respectively, -7.89% and +30.42% for c-terminal PTH (P = 0.022), -4.39% and +38.88% for i-PTH (P = 0.077), and +3.68% and +30.52% for midregion PTH (P = 0.099). The similar changes were observed in the falecalcitriol group during period 2, confirming the reproducibility. Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels.

Adult↗

PubMed1998

Seasonal rise in interleukin-4 during pollen season is related to seasonal rise in specific IgE for pollens but not for mites.

Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.

Adolescent↗

PubMed1998

Soluble vascular cell adhesion molecule-1 in perennial allergic rhinitis.

Since the expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells plays a central part in the selective recruitment of eosinophils into allergic inflammatory lesions, VCAM-1 may be a key molecule in allergic inflammatory diseases. Soluble forms of VCAM-1 (sVCAM-1) have recently been identified in the circulation, but there is limited published information on levels of sVCAM-1 in the circulation. If the levels of sVCAM-1 vary between patients with allergic diseases and normal controls, this variance would be very useful to investigate the state of the allergic disease and underlying inflammation. This study investigated the serum sVCAM-1 level in patients with perennial allergic rhinitis (rhinitis group) in comparison with non-atopic healthy volunteers (control group). No significant difference in the serum sVCAM-1 level was seen between the two groups (p = 0.4342). However, the serum sVCAM-1 levels in the severe rhinitis group were significantly higher than those in both the control group (p = 0.0067) and the mild rhinitis group (p = 0.0015), whereas no significant difference was observed between the mild rhinitis group and the control group (p = 0.1113). In addition, the serum levels of sVCAM-1 were significantly correlated with the nasal symptoms in the rhinitis group (rs = 0.486, p < 0.0001). In conclusion, serum concentrations of sVCAM-1 are increased in patients with severe perennial allergic rhinitis, and measurement of sVCAM-1 concentrations in sera is likely to be a useful tool for investigation of the severity of allergic rhinitis and underlying inflammatory reactions.

Animals↗

PubMed1998

Interleukin-6 and tumour necrosis factor alpha synthesized by cholesteatoma cells affect mucociliary function in the eustachian tube.

The aims of this study were to investigate the possible synthesis of IL-6 and TNF-alpha by cholesteatoma cells in culture and the effect of IL-6 and TNF-alpha produced by cultured cholesteatoma cells on the function of the mucociliary system in the tubotympanum. Cholesteatoma cells were collected from 10 patients, and the medium supernatants in which cholesteatoma cells or normal human epidermoid cells had been cultured for 48 h were collected. The concentrations of IL-6 and TNF-alpha in the supernatants were measured by enzyme-linked immunosorbent assays. The effect of the culture supernatants on ciliary activity was examined using an in vitro experimental system. The supernatants were injected into the tympanic cavities of guinea pigs, and mucociliary clearance time of the Eustachian tube was determined according to our dye transport technique 24 h after the intratympanic injection. Human cholesteatoma cells produced larger amounts of IL-6 and TNF-alpha than normal human epidermoid cells. The supernatants of cholesteatoma cells compromised ciliary activity and mucociliary clearance of the Eustachian tube in the guinea pigs. The effects of the supernatants of cholesteatoma cells on the ciliary activity and mucociliary clearance were correlated with the concentration of IL-6 and TNF-alpha in the supernatants. In conclusion, cholesteatoma cells can produce IL-6 and TNF-alpha, which are able to compromise the mucociliary function in the tubotympanum. IL-6 and TNF-alpha produced in middle ear cholesteatoma might aggravate the disease by the wide range of their biological activities on the mucociliary system, the proliferation of cholesteatoma cells and the bone metabolism.

Adult↗

PubMed1998

Suppression of seasonal increase in serum interleukin-5 is linked to the clinical efficacy of immunotherapy for seasonal allergic rhinitis.

Although immunotherapy is recognized as a highly effective form of treatment for allergic rhinitis, especially pollen-induced seasonal allergic rhinitis, the mechanisms have not been fully established. In the present study, we investigated whether immunotherapy could affect the seasonal increase in interleukin-5 (IL-5) in the serum of patients with seasonal allergic rhinitis and whether the effect on IL-5 in serum is related to the clinical efficacy of immunotherapy. Venous blood was collected twice from each patient with seasonal allergic rhinitis due to Japanese cedar pollens, before and during the cedar pollen season in 1997, to determine the cedar pollen-specific IgE and IL-5 in serum. Both specific IgE and IL-5 in serum were significantly increased during the pollen season, not only in the poor responders to antihistamines but also in the good responders. Neither the rate of seasonal increase in specific IgE nor the rate of seasonal increase in IL-5 differed significantly between the good responders and the poor responders to antihistamines. Both specific IgE and IL-5 were significantly increased during the pollen season in the poor responders to immunotherapy, whereas neither specific IgE nor IL-5 was increased during the pollen season in the good responders to immunotherapy. The rate of seasonal increase in specific IgE as well as IL-5 was significantly smaller in the good responders than in the poor responders to immunotherapy. The rates of seasonal increase in specific IgE and in IL-5 were inversely correlated with the length of time on immunotherapy. However, the rate of seasonal increase in specific IgE was not significantly correlated with the rate of seasonal increase in IL-5. In conclusion, the suppression of the seasonal increase in IL-5 in serum is a working mechanism of immunotherapy related to the clinical efficacy of the treatment.

Adult↗

PubMed1998

Seasonal changes in phytohemagglutinin-induced cytokine synthesis by peripheral blood lymphocytes of patients with seasonal allergic rhinitis due to Japanese cedar pollens.

We investigated the seasonal changes in non-specific stimulation-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in patients with seasonal allergic rhinitis due to Japanese cedar pollen. This study included 16 non-allergic healthy adult volunteers and 115 patients with detectable levels of Japanese cedar pollen-specific IgE in their serum. The 115 patients were divided into five groups, an asymptomatic group (specific IgE was positive but there were no nasal symptoms), a medication group (typical symptoms of Japanese cedar pollinosis and treated with antihistamine tablets), a good-IT group (responded well to immunotherapy), a poor-IT group (responded poorly to immunotherapy) and a cure group (no symptoms after discontinuation of immunotherapy). PBMCs (1.0 x 10(6) cells/ml) were collected before and during the cedar pollen season in 1998, and were cultured for 24 h in the presence of 10 micrograms/ml phytohemagglutinin. The concentrations of IL-4, IL-5 and IFN-gamma in the culture supernatants were measured by an enzyme-linked immunosorbent assay. None of the levels of IL-4, IL-5 and IFN-gamma synthesized by PBMCs in the asymptomatic group, medication group, good-IT group, poor-IT group or cure group were significantly different from those in the non-atopic group. In the medication group, the synthesis of TH2-type cytokines (both IL-4 and IL-5), but not of TH1-type cytokine (IFN-gamma) was significantly increased during the pollen season compared with before the pollen season, whereas in the non-atopic group, the synthesis of IL-4, IL-5 and IFN-gamma did not differ significantly before and during the pollen season. The synthesis of both IL-4 and IL-5 was significantly increased during the pollen season in the poor-IT group, whereas the synthesis of IL-4 and IL-5 was not increased during the pollen season in the good-IT or cure groups. In conclusion, our study demonstrates that T-cell reactivity to non-specific stimulation outside of the pollen season did not differ between the patients with seasonal allergic rhinitis and non-atopic individuals, that T-cells in patients with seasonal allergic rhinitis are affected or primed by the natural pollen exposure to synthesize TH2-type cytokines even in response to non-specific stimulation, and that successful immunotherapy could decrease the natural pollen exposure-primed hyperreactivity of TH2 cells to non-specific stimulants.

Adult↗

PubMed1998

Allergen-specific immunotherapy for allergic rhinitis: a new insight into its clinical efficacy and mechanism.

Immunotherapy has been used widely for allergic diseases for more than 90 years but, in the opinion of many physicians, it is still a controversial form of treatment. The exact mechanism of action of immunotherapy remains to be determined. In the present study, we review the clinical efficacy and mechanism of action of immunotherapy for allergic rhinitis. Recent double-blind placebo-controlled studies have demonstrated the clinical efficacy of immunotherapy for allergic rhinitis. This therapeutic method has several advantages over conventional pharmacological treatment. Immunotherapy is inferior to pharmacological treatment in the short term, but in the long term it is substantially superior with respect to clinical efficacy. Immunotherapy has the potential permanently to alleviate the abnormal immunological responses of allergic rhinitis and to cure the nasal symptoms in the long term, even after discontinuation of injections. In addition, immunotherapy can prevent the onset of new sensitizations in allergic patients and may prevent the progression of rhinitis to asthma. It may therefore be possible for immunotherapy to alter the natural history of allergic sensitization and its clinical manifestation. These lines of clinical evidence could affect strategies of long-term therapy for allergic rhinitis. Modern molecular biological techniques have suggested that immunotherapy may affect allergen-induced TH responses or cytokine profiles, but there is no general agreement among investigators. However, IL-5 is likely to be the most important cytokine involved in the clinical efficacy of immunotherapy, and the suppression of allergen-induced IL-5 synthesis is most likely to be involved in the mechanism of immunotherapy. Our recent investigations, focusing on specific IgE and IgG4 responses, suggest that immunotherapy-induced changes in these specific antibodies play a clinical role and are involved in the mechanism of action of immunotherapy. It is probable that immunotherapy modulates and affects many different immunological and non-immunological phenomena to produce clinical efficacy and that clinical improvement is a consequence of different mechanisms over time.

Allergens↗

PubMed1998

Fluorine-18 fluorodeoxyglucose positron emission tomography imaging of parotid mass lesions.

Using X-ray CT or magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies were performed in 28 patients with parotid lesions. All lesions except two showed higher accumulation of FDG than normal parotid gland. High accumulation was found in all of 5 carcinomas, all of 6 Warthin's tumors, and 8 of 12 pleomorphic adenomas, with standardized uptake values (SUVs) over 3.0. The mean SUVs of carcinomas, Warthin's tumors, and pleomorphic adenomas were 5.92 +/- 2.05, 7.03 +/- 2.49, and 4.07 +/- 1.55, respectively. On the other hand, all 5 inflammatory lesions demonstrated low accumulation, with mean SUVs of 1.66 +/- 0.89. It is thus difficult to differentiate malignant from benign parotid lesions by SUV on FDG-PET.

Adult↗

PubMed1998

Roxythromycin reinforces epithelial defence function in rabbit trachea.

Our study elucidates the effect of roxythromycin (RXM) on airway epithelial defence functions, especially the mucociliary and epithelial barrier functions, in the rabbit trachea. In vitro ciliary activity was not affected in the presence of 3.3 mg/ml of RMX, but was enhanced in the presence of 6.7 mg/ml of RXM. Oral administration of 10 and 100 mg of RXM for 14 days enhanced both ciliary activity and mucociliary transport velocity in the trachea. Epithelial permeability to fluorescein isothiocyanate-dextrans (FD-70s; molecular weight: 70,000 daltons) was not affected by oral administration of 10 mg of RXM for 14 days, but was significantly reduced by oral administration of 100 mg of RXM for 14 days. Inhalation of platelet activating factor (PAF) compromised the function of the mucociliary system and the tight junction barrier. However, pretreatment with 20 mg of RXM significantly alleviated the PAF-induced decrease in mucociliary function and the increase in epithelial permeability to FD-70s. In conclusion, such reinforcement of the epithelial defence functions is likely to be involved in the pharmacological action underlying the clinical efficacy of RXM for chronic airway inflammatory disease.

Animals↗

PubMed1998

Homozygosity mapping of a gene responsible for gelatinous drop-like corneal dystrophy to chromosome 1p.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disorder characterized clinically by grayish corneal deposits of amyloid and by severely impaired visual acuity. Most patients require corneal transplantation. To localize a gene responsible for GDLD, we performed linkage analysis of 10 consanguineous Japanese families with a total of 13 affected members. Homozygosity mapping provided a maximum LOD score of 9.80 at the D1S2741 marker locus on the short arm of chromosome 1. Haplotype analysis further defined the disease locus within a region of approximately 2.6 cM between D1S2890 and D1S2801.

Chromosome Mapping↗