Neural and glial cells in the olfactory bulb of rats were reported to regenerate even after birth. We studied cell division dynamics the guinea pig olfactory bulb using immunohistochemical double staining. Anti-bromodeoxyuridine (BrdU) antibody for detecting dividing cells, anti-calbindin antibody, antiprotein gene product antibody for neural cells, and anti S-100 antibody for glial cells were used immunohistochemical staining.
At 1 hour after BrdU injection, many BrdU-labeled cells were present in the subventricular zone. BrdU-labeled cells migrated from the subventricular zone to the subependymal zone of the olfactory bulb through rostal migratory pathway within 5 days. Labeled cells then moved peripherally from the bulb zone differentiated neural cells and filial cells in some layers.

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The manipulation to open the ostium of paranasal sinus promotes the drainage of secretions and the ventilation of sinus. At the same time, paranasal sinus inflammation is healed by the action of topical drug nebulization through the nasal cavity.
The purpose of this study is to reconfirm the importance of its manipulation. Before and after manipulation to open the ostium of paranasal sinus, the intranasal nebulization of water soluble contrast medium was carried out and then computed tomography (CT) was taken (study 1). In the same way, CT was taken after the infusion of medium by the YAMIK sinus catheter (study 2).
I examined the amount of water soluble contrast medium transferred into the nasal sinuses (mainly the maxillary sinus) by CT image. I focused on cases of paranasal sinusitis in which middle nasal meatus is free of nasal polyps (paranasal sinusitis group). Controls were subjects with nasal cavity findings and sinusitis (normal group).
In the study of nebulizaion, the enlargement of the ostium was recognized by CT image. But tansition in medium to maxillary sinus was confirmed neither in the paranasal sinusitis group nor in the normal group. It may be said that I couldn't detect the contrast medium by CT image because the mucous membrane of maxillary sinus in normal group was very thin and the transition of the contrast medium was very small.
It the study of YAMIK sinus catheter, transition in contrast medium to maxillary sinus was confirmed in the normal group on the side given the open manipulation technique. The patients with slight sinusitis showed the slight to moderate transition in medium. In the patients with moderate sinusitis, the transition was very small. It is suggested that manipulation to open the ostium of paranasal sinus is the useful method to carry out the conservative therapy for slight paranasal sinusitis.

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The clinical value of allergen-specific immunotherapy in treating nasal allergy has been established in Europe, but not yet in Japan, because allergen-vaccine for Japanese cedar is still under development and double-blind placebo-controlled studies have not been done. We studied the percentage reduction of symptom/medication scores in the treatment of allergen-specific immunotherapy for nasal allergy and determined the percentage of patients treated effectively for allergen-specific immunotherapy. We estimated the degree of patient satisfaction. Documentation of the clinical effect of such immunotherapy is based on 6 double-blind placebo-controlled studies of house dust mite allergy and 9 double-blind placebo-controlled studies of pollinosis.
In at least 50% of patients with nasal allergy, nasal symptoms decreased to 50% of the pretreatment level in allergen-specific immunotherapy. Some 25% patients with nasal allergy found such immunotherapy highly satisfactory and at least 50% found it moderately satisfactory. Allergen-specific immunotherapy thus clearly decreases medication scores in patients.

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A 71-year-old man with drooping right superior palpebra reported orbital pain with deficits in the optic, oculomoter, trochlear, and abducens nerves but no nasal symptoms. Magnetic resonance imaging (MRI) showed a cavernous sinus abnormality and a soft tissue mass in the anterior ethmoid sinus. The first diagnosis was Tolosa-Hunt syndrome, and corticosteroid treatment was instituted. His response to corticosteroid treatment was poor and the anterior ethmoid mass was examined, resulting in a pathological diagnosis of non-Hodgkin malignant lymphoma, clinical stage IV A due to involvement of bone marrow. We assume that the cavernous sinus abnormality was due to malignant lymphoma.

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Th2 lymphocytes producing IL-4, 5 play a crucial role in the pathogenesis of many allergic disorders. IL-4 plays an especially important role in differentiation of the Th2 phenotype. B7-2 (CD86) is reported to play a crucial role in differentiation of the Th2 phenotype. The effects of CD86 on IL-4 production remain unclear, however, in atopic diseases.
We studied cytokine production profiles of by peripheral blood mononuclear cells (PBMCs) in Japanese cedar pollinosis (JCP) subjects after in vitro stimulation.
PBMCs were isolated from 20 JCP and 12 control subjects and stimulated with Japanese cedar pollen extract. Th1 and Th2 cytokine production was measured by ELISA. The surface expression of IL-4 on CD4⁺ cells was assessed using flow cytometry in the presence or absence of anti-CD86 mAb.
After in vitro stimulation, significantly higher levels of IL-5 were produced by PBMC of JCP subjects than controls (p=0.01). In contrast, significantly higher levels of IFN-γ were produced by PBMCs of controls than JCP subjects (p=0.01). The surface expression of IL-4 on CD4⁺ cells was significantly upregulated following stimulation in JCP subjects compared to controls. The surface expression of IL-4 on CD4: cells was inhibited by anti-CD86mAb.
These results indicate that the Th2 response is predominant in JCP subjects after in vitro allergen stimulation and that IL-4 may function to some degree. CD86may be costimulatory molecules in allergen-induced IL-4 production.

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Six patients with well-documented histories of seasonal allergic rhinitis caused by Japanese cedar pollen were allocated randomly on a single-blind basis to receive either sublingual immunotherapy (SL-IT) with a solution of purified allergen preparation (Hollister Stier) or a matched placebo for 24 weeks from 1998 to 1999. The SL-IT effect was assessed based on the symptom medication score (SMS). Actively treated patients tended to have a lower SMS during the pollen season than the placebo group. The same six patients were treated by active allergen from 1999 to 2000. SMS of these patients was compared to the SMS of matched patients treated by medication alone. SL-IT-treated patients had lower SMS during the 3 weeks of the pollen season than the medication group. Side-effects were negligible.
The stimulatory index (SI) of PBMC by antigen stimulation was also studied to determine the SL-IT mechanism in the first experiment. The SI of 2 patients in the actively treated group rose early in the pollen season. The SI in the placebo group did not, however, indicating the effectiveness of SL-IT related to general immunization. We concluded that SL-IT with Japanese cedar pollen extract in patients with Japanese cedar pollinosis is as effective as when used overseas.

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Since 1986, we have conducted chemosurgery using trichloracetic acid (TCA) on nasal turbinates to treat nasal allergy. We studied long-term treatment results measuring kallikrein activity in nasal lavage in 24 patients with Japanese ceder pollen allergy ranging from 24 to 51 years of age (mean: 34.4). They underwent TCA surgery 2 to 10 years (average: 7 years 2 months) prior to the present study. Clinical findings were obtained in the peak ceder pollen dissemination season, and nasal lavage from 10 of the 24 during ceder-pollen-free season. We found that allergy-specific symptoms generally improved after surgery in that only 1 had very severe and 2 severe symptoms in the peak season, compared to 5 with mild and 16 with slight symptoms, although 5 had had very severe, 9 severe, and 10 mild symptoms before surgery. Half of the 24 no longer required antiallergenic drugs after surgery. Kallikrein activity was 4.77±2.64×10^-10mol/ml/min before surgery and dropped significantly to 0.97±0.63×10^-10mol/ml/min after surgery (p<0.05).

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To evaluate the efficacy of allergen-specific immunotherapy in the treatment of seasonal allergic rhinitis, we reviewed 35 studies that examined the clinical efficacy of immunotherapy using double-blind placebo-controlled trials. Of the 35, 32 reported that immunotherapy was significantly effective (p<0.05) compared to placebo. These studies reported that median clinical efficacy is 45% and symptoms decreased by almost half.
Some changes in nasal mucosa conditions and peripheral blood mononuclear cells after immunotherapy have been clearly described. Double-blind placebo-controlled trials have shown that clinical efficacy continues for a few years after the immunotherapy series.
We could not metanalyze clinical efficacy of immunotherapy for seasonal allergic rhinitis because of the few paper published in Japan suitable for metanalysis, nor could we conduct double-blind placebo-controlled immunotherapy trials for seasonal allergic rhinitis in Japan. In a study of Japanese cedar pollinosis patients, immunotherapy was effective in 60 to 89% of patients, although these studies were not placebo-controlled trials.
For 4 consecutive years, we have observed Japanese cedar pollinosis patients undergoing 18-month immunotherapy using pullulan-conjugated antigen compared to medication group.
We carefully examined some clinical factors including evaluation by symptom medication score and personal patient evaluations. These factors seemed to be positively correlated. Neither the change in serum specific-IgE nor the change in serum specific-IgG4 was related to clinical efficacy. Our results suggested that the change in the production of IL-4 and IL-5 from mononuclear cells stimulated by antigen in vitro is a good indicator of immunotherapy efficacy.

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