Biomedical subjects
Publications and source records attributed to M Okuda.
Our recent studies of nasal histamine sensitivity in nasal allergy are presented. The sensitivity differed according to the site and size of the nasal mucosa and was correlated with the degree of provocation reaction to antigen. This sensitivity appears to be established in childhood and strongly correlated with the increased sensitivity of histamine receptors as well as the autonomic nervous system dysfunction of the nose.
The mode of action of topical steroid therapy was investigated in connection with the effects of beclomethasone nasal spray on the three important factors in allergic nasal manifestation: 1) the number of basophilic cells (blood basophils and tissue mast cells) in the nasal mucosa, 2) the sensitivity of the basophilic cells to allergen and 3) the mucosal sensitivity to histamine. The results indicated that of the three factors the inhibition in the accumulation of basophilic cells in the mucosal surface was the most important mode of action of beclomethasone nasal spray.
The tissue blood flow of the nasal mucosa in normal subjects and patients with nasal allergy was studied by the hydrogen clearance method. The flow in the inferior turbinate in normal subjects and patients with nasal allergy did not differ. The test results were highly reproducible and were almost the same in different anterior parts of the inferior turbinate. The effects of nasal spray with vasoconstrictor and nasal provocation by an allergen-containing paper disc on the blood flow of the inferior turbinate were examined in normal subjects and patients with nasal allergy. The flow decreased remarkably after spray with vasoconstrictor. The flow also decreased remarkably in the mucosal membrane close to the area of contact of the allergen disc, whereas it increased at the area 10 mm away from the disc. The hydrogen clearance method is useful for clinical studies of nasal circulation.
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The aim of the present study has been to examine the pathophysiology of allergic rhinitis, and the number, distribution and antigen-reactivity of basophilic cells. Blown nasal secretions, nasal washings, scrapings and excised specimens of nasal mucosa were collected and examined cytologically and histologically in both light and electron microscopes. Antigen-induced histamine release was also studied in these specimens. The results indicate that migration of basophilic cells (mainly basophil leukocytes in the nasal secretion and predominantly mast cells in the epithelium) to the mucosal surface is characteristic for allergy and that the total number and the histamine content of these cells are sufficient to produce the nasal manifestation of allergy. In conclusion, this study provides evidence supporting our concept of the mechanism of nasal allergy, i.e., that allergic reaction to inhaled allergens is initiated on the mucosal surface, and not in the lamina propria.
The microsomal fraction of the rat brain had been subfractionated by a sucrose density gradient centrifugation into three distinct membrane fractions, namely "light smooth-surfaced membrane" LSM, "heavy smooth-surfaced membrane" HSM, and "rough-surfaced membrane". They were different in their chemical compositions and enzymatic activities as well as their buoyant densities. In the present experiment antisera to purified LSM and HSM were raised in rabbits to characterize the two membranes immunochemically and immunohistochemically. Antigenicity of these membranes was studied by using [125I]-protein A autoradiography and immunohistochemical localization of the antigens in the rat brain was revealed by the indirect immunoperoxidase technique. By [125I]-protein A autoradiography (Fig. 1), differences in the antigenicity between LSM and HSM were clearly shown. Two out of nine antisera to LSM were relatively specific to LSM; anti-LSM #8 serum detected a protein band of Mr 53,000 which is relatively specific to LSM (Fig. 1 B-a) and anti-LSM #9 serum reacted with three proteins specific to LSM (Mr 53,000, Mr 46,000, and Mr 27,000) (Fig. 1 C-a). However, anti-HSM sera did not discriminate between LSM and HSM antigens (Fig. 1 D & E) and non-immune serum did not detect any antigen at all (Fig. 1 F). Indirect immunoperoxidase pattern by anti-LSM #8 revealed heavy staining of the neuropil in the cortices of cerebrum, hippocampus and cerebellum (Fig. 2 A, B & C). The perivascular structures identical to glial end-feet were also stained but the cell bodies and dendritic trunks of the neurons were not stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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Differences in the susceptibilities to sodium saccharin of the urinary bladder epithelium in various strains of rats and other animal species were examined. In Experiment 1, male ACI, Wistar, F344 and Sprague-Dawley rats were administered 5.0% sodium saccharin in the diet for 52 weeks. Rats were killed after weeks 12, 24, 36 and 52. In ACI rats, sodium saccharin induced not only preneoplastic lesions of the urinary bladder, but also tumors. However, in other strains it did not. The urinary bladder of ACI rats given sodium saccharin had the most marked lesions under scanning electron microscopy, with less marked changes in Wistar and F344 rats. Sprague-Dawley rats were resistant to sodium saccharin. In Experiment 2, male F344 rats, B6C3F1 mice, Syrian golden hamsters, and Hartley guinea pigs were given 5.0% sodium saccharin in the diet for 20 weeks. The animals were sacrificed sequentially. Rats developed urinary bladder lesions during the experiment, as detected by light microscopy and scanning electron microscopy. Increased DNA synthesis of the urinary bladder epithelium was detected in rats by autoradiography. However, mice, hamsters and guinea pigs were resistant to sodium saccharin. These results indicate that there are strain and species differences in the urinary bladder response to sodium saccharin.
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The effect of partial cystectomy on the occurrence of pre-neoplastic lesions, papillary or nodular hyperplasia (PN hyperplasia), of the bladder in male F344 rats was studied in an experiment in which bladder carcinogens and promoters were given to the rats after initiation with BBN. The bladder carcinogens tested were N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and N-4[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and the bladder promoters were sodium saccharin, sodium cyclamate, and DL-tryptophan. Partial cystectomy significantly decreased the occurrence of PN hyperplasia in rats treated with EHBN and tended to inhibit that in rats given saccharin or tryptophan. Thus partial cystectomy inhibited rather than enhanced the induction of PN hyperplasia.
Trypsin was found to generate depressor substances from human plasma protein fraction IV-4 at all pH values from 2.0-10.0. The depressor substances generated at three representative pH values, i.e., 3.2, 5.0, and 8.0 were purified and isolated. The procedures used for the isolation were: (a) gel-filtration through Sephadex G-25; (b) desalting by ion retardation chromatography on AG 11 A8; (c) equilibrium chromatography on SP-Sephadex C-25; (d) desalting by AG 11 A8 again, and (e) partition chromatography on a high pressure liquid chromatograph. Upon high pressure liquid chromatography, the depressor substances formed at each of the three pH values were separated into two fractions. In thin layer electrophoresis, the two depressor substances moved with mobilities identical with those of synthetic bradykinin and synthetic [des-Pro3]-bradykinin but not those of methionyl-lysyl- or lysyl-bradykinin. The amino acid analysis of the hydrolysate of the depressor substance 1 generated at pH 3.2 showed the following proportional composition: Arg, 2; Pro, 2; Gly, 1; Phe, 2; Ser, 1. The product thus lacked 1 mol of proline residue as compared with bradykinin, and the retention time of this depressor substance 1 was identical with that of synthetic [des-Pro3]-bradykinin on high pressure liquid chromatography. The depressor substance 2 showed Arg, 2; Pro, 3; Gly, 1; Phe, 2; Ser, 1. This is identical with the composition of bradykinin. Finally, substances 1 and 2 showed oxytocic activities identical to those of synthetic [des-Pro3]-bradykinin and synthetic bradykinin, respectively. Substance 1 showed a bradykinin-potentiating activity similar to that of synthetic [des-Pro3]-bradykinin.
Clinicopathological features of three male cases with malignant histiocytosis (MH) are described. Case 1, aged 27, had had an indurated swelling of the left mandibular region, histologically being chronic lymphocytic inflammation, with ebb and flow for 4 years prior to the onset of MH, with low grade fever, lymphadenopathy and pulmonary infiltration. Histology of the lymph node was compatible with MH, and only a temporary improvement was obtained by COP therapy. Case 2, aged 32, showed acute febrile onset with severe anemia and splenomegaly. Diagnosis of MH was determined by bone marrow histology. COP therapy appeared effective, but caused severe leukopenia and thrombocytopenia resulting in fatal gastrointestinal bleeding. Case 3, aged 16, had high fever and cutaneous mass of the left chest wall, histology of which suggested MH. Bone marrow biopsy was also diagnostic. Severe pancytopenia allowed only a limited therapy. Morphology of the histiocytes was variable in each case. Diffuse infiltration of neoplastic histiocytes in many organs and erythrophagocytosis in the bone marrow were commonly found in all the cases. The present cases suggested a diagnostic value of bone marrow biopsy and possible effect of antineoplastic combination therapy on earlier stage of MH.
Cefmetazole (CMZ) was compared to cefazolin (CEZ) for efficacy and safety in the treatment of suppurative otitis media (including acute otitis media and chronic otitis media in acute aggravating stage) under well controlled clinical trials. The therapeutic effects were analyzed statistically in 172 patients (82 administered CMZ, 90 administered CEZ). The adverse reactions were also analyzed statistically in 199 patients (CMZ 99, CEZ 100) in whom the judgement was possible. 1. The efficacy rate of CMZ (72.3% for good to excellent response) was assessed by physicians in charge to be similar to that of CEZ (59.3%). This was the same being assessed by the committee, too (CMZ 64.6%, CEZ 56.7%). 2. When patients were classified into 2 groups (acute otitis media, chronic otitis media in acute aggravating stage) with respect to diagnosis, statistically significant difference in clinical efficacy assessed by physicians in charge was observed in the cases with chronic otitis media (CMZ, CEZ). In addition, the improvements of flares on the drum membrane and the mucous membrane of eardrum were significantly better in the CMZ group than in the CEZ group. 3. Bacteriologically, 16 cases (19.8%) of S. aureus were resistant to CEZ, while only 1 case (1.2%) to CMZ. CMZ was judged to be effective in 5 of the 6 cases in which CEZ-resistant strains were detected. 4. Side effects were found in 2 cases (2.0%) treated with CMZ: one complained of retching and abdominal pain and the other developed skin eruption. On the other hand, only 1 case (1.0%) developed skin eruption in the CEZ group. These results suggest that CMZ is a new antibiotic agent which is highly valuable in the treatment of suppurative otitis media.