Biomedical subjects
Publications and source records attributed to M Tamai.
A 43-year-old man had a silent intraocular foreign body at the ciliary body that was composed of iron. Siderosis bulbi was observed after an extracapsular cataract extraction with intraocular lens implantation was performed. The mechanical forces applied during the surgery might have been responsible for liberating the ferrous ion into the globe.
From a cultured broth of Streptomyces matensis A-6621, we isolated three new platelet aggregation inhibitors designated as PI-080, PI-085 and PI-087. The structures of these compounds were established by spectral and chemical methods.
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Two new nortriterpenoid saponins, named yemuoside YM10 (I) and YM12 (II), were isolated from Stauntonia chinensis Decne. A new prosaponin (VI) was isolated from the cleavage of ester-glycoside linkage. Their chemical structures were elucidated by means of chemical and spectrometric analysis. Yemuoside YM10 (I): C58H92O25, a white powder, mp 215-219 degrees C (dec), [alpha]D20-4.41 degrees (c 0.272, CH3OH). Its structure was found to be 28-O-alpha-L-rhamnopyranosyl- (1----4) -beta-D-glucopyranosyl- (1----6) -beta-D-glucopyranosyl ester of 3-O-alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl-30-+ ++norolean-12, 20 (29) -dien-28-oic acid. Yemuoside YM12 (II): C52H82O21, a white powder, mp 200-204 degrees C (dec.), [alpha]D20 + 10.12 degrees (c 0.346, CH3OH). Its structure was found to be 28-O-beta-D-glucopyranosyl- (1----6) -beta-D-glucopyranosyl ester of 3-O-alpha-L-rhamnopyranosyl- (1----2) -alpha-L-arabinopyranosyl-30-norolean-12, 20 (29)-dien-28-oic acid. Prosaponin (VI): C40H62O11, a white powder, mp 243-246 degrees C (dec.), [alpha]D22 + 12.13 degrees (c 0.128, CH3OH). Its structure was found to be 3-O-alpha-L-rhamnopyranosyl- (1----2)-alpha-L-arabinopyranosyl-30-norolean-12, 20 (29)-dien-28-oic acid.
A 60-year-old woman was admitted to our hospital in June 1985, complaining of fever, cough and right lower chest pain, with a five-year history of asymptomatic primary biliary cirrhosis. Chest X-ray on admission showed an infiltrative shadow in the right lower lung field. She was first treated with various antibiotics unsuccessfully. Hemoptysis continued. Dyspnea and anemia appeared. Chest X-ray 17 days after admission showed multiple infiltrative shadows in the both lung fields. She was treated with steroid pulse therapy successfully. During prednisolone treatment decreasing nodular shadows with cavities appeared on chest X-ray. An open lung biopsy was performed in March 1986. The histologic findings showed a necrotizing vasculitis with granuloma and perivascular fibrosis. She was treated with prednisolone and prednisolone-azathioprine therapy unsuccessfully, but successfully with prednisolone-cyclophosphamide therapy. This case was a rare case of Wegener's granulomatosis with transition from fulminant type to granulomatous type. No similar case of Wegener's granulomatosis with asymptomatic primary biliary cirrhosis has been reported in the literature.
Fifty-one cases of malignant lymphomas in patients under 20 years of age have been reviewed in Osaka, Japan. The breakdown of these cases revealed 6 cases (11.8%) of Hodgkin's disease (HD) and 45 cases (88.2%) of a non-Hodgkin's lymphoma (NHL). Both the HD and NHL cases were determined by using the Rye classification, as well as the Rappaport, Kiel, and LSG classifications, respectively. The results have shown that (1) the incidence of HD in childhood is the same as that seen in the adult in Japan; (2) that a NHL of the nodular type is rare in Japan as it is in Western countries; (3) that any significant differences were not present in the distribution of each histologic subtype in the cases of a NHL among Japan and Western countries, and that the lymphoblastic type was the most common. From this study it is concluded that geographical differences were not a factor in comparing cases of childhood malignant lymphomas in Japan and Western countries.
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A 4-year-old girl had a cavernous hemangioma of the retina in the right eye. A vitreous hemorrhage associated with this lesion caused amblyopic exotropia. Although this lesion has been considered harmless, it may cause visual impairment in the pediatric patients.
Between February 1986 and April 1987, we conducted a phase II clinical trial of a three-drug combination of ifosfamide, cisplatin, and vindesine in advanced non-small-cell lung cancer. The combination consisted of ifosfamide, 1,300 mg/m2, on days 1 through 5, cisplatin, 20 mg/m2, on days 1 through 5, and vindesine, 3 mg/m2, on days 1 and 8. Courses were repeated at 4-week intervals until disease progression or unacceptable toxicity occurred. Of 21 patients evaluated, one had a complete response and 12 had partial response, with an overall response rate of 62%. The projected median response duration was 30 weeks. The median survival for all patients has not been reached: 14 of 21 patients are still alive with a median follow-up period of 41 weeks (range, 12 to 73 weeks). The major toxicity was myelosuppression. One patient died of septicemia while neutropenic, but the toxicity was well tolerated in the rest. These results indicate that this three-drug combination is active against non-small-cell lung cancer and warrants further clinical trials.
Dimethyl-4, 4'-dimethoxy-5, 6, 5'-6'-dimethylenedioxybiphenyl-2, 2'-dicarboxylate (DDB) is a synthetic analogue of Schizandrin C, an active compound isolated from a Chinese herb, Fructus schizandrae. We administered this compound to dystrophic hamsters in vivo for 31 days. This led to a 61% reduction of the calcium content, an 86% reduction of the area of calcium deposits, and a 52% reduction of the area of necrosis of cardiac muscle. However, skeletal muscle necrosis was not significantly improved. No clear change in plasma creatine kinase (CK) was observed. In an in vitro incubation study, the rate of CK release and tetanus tension of the extensor digitorum longus muscle of dystrophic hamsters were not substantially changed by the addition of DDB. This study suggests that DDB has some effect on cardiac necrosis, and that it might be useful for treatment of the cardiac involvement in patients with muscular dystrophy or other conditions with accompaning Ca accumulation.
Cells identical to Leydig cells were found within a peritubular boundary layer and even inside a basal lamina of seminiferous tubules in three male patients (two with inguinal cryptorchism and one with infertility). The seminiferous tubules of all patients showed a moderate to marked thickening of the boundary layer and a complete loss of spermatogenic cells. The "ectopic Leydig cells" were characterized by the presence of Reinke crystals or an extensively developed smooth endoplasmic reticulum. These cells were believed to have differentiated in situ from myoid cells within the boundary layer and also to have invaded from the interstitial tissue in the form of mature Leydig cells. The occurrence of ectopic Leydig cells appeared to parallel the extent of loss of the Sertoli cells and also that of the thickening of the boundary layer. The functional significance of the ectopic occurrence might be implicated in the impaired spermatogenesis.
Two patients with neovascular glaucoma presented an obstruction in the internal carotid artery and reverse flow of blood through the ophthalmic artery, a so-called ophthalmic artery steal phenomenon, on digital subtraction angiography. To study the cerebral metabolic state maintained by this mechanism, the same patients underwent positron emission tomography. Both displayed decreased regional cerebral blood flow, reduced regional cerebral metabolic rate for oxygen and for glucose and increased regional oxygen and glucose extraction ratios. In our patients with chronic ocular ischemia, the cerebral perfusion maintained by the ophthalmic artery steal phenomenon was in the critical state called misery perfusion.
We studied the effect of loxistation (EST), an orally applicable cysteine proteinase inhibitor, on dystrophic hamsters, UM-X7.1.E-64-c, an active form of EST, was continuously found in plasma when the feed containing EST was given ad libitum. The drug concentration in plasma of dystrophic hamsters receiving EST feed showed distinct dose dependency. A diet containing EST from weaning to death significantly prolonged the survival period of the dystrophic hamsters.
Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81% (29% complete) and the 2 year survival rate was 28.6%. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000cGy) and 3 received surgical treatment. Radiation therapy improved the 2-year survival rate (42.2%) when compared with those patients who received no radiation therapy (18.2%). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy.
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Homotransplantation of preserved sclera was successfully performed for post-traumatic scleral staphyloma in a 38-year-old woman with Ehlers-Danlos syndrome type VI. The transplanted tissue was preserved by glycerol dehydration. For 1 year postoperatively, no sign of graft failure or recurrence of scleral staphyloma has been found. To our knowledge, this is the first report of the use of a preserved scleral homograft to treat this ocular complication in a patient with Ehlers-Danlos syndrome.
In the present study, 96 cases of HD selected from 937 cases of malignant lymphomas in Osaka, Japan were reviewed to evaluate a time trend of HD. The results showed that, during the periods from 1964-74 to 1975-85, (1) ratio of HD among all malignant lymphomas decreased from 14.8% to 8.9%, (2) MC decreased and NS increased, and (3) the age of onset fell.
E-64 isolated from a culture of Aspergillus japonicus is a specific inhibitor of cysteine proteinases. E-64-c, a synthetic analog of E-64, was effective in model animals of muscular dystrophy only when it was given intraperitoneally and by means of osmotic minipump. It showed no effects due to its low absorbability from intestine when it was administered orally. EST, the ethyl ester of E-64-c, was expected to be readily absorbed through intestinal membrane, since it is more lipophilic than E-64-c. Both EST and E-64-c have a high specificity to cysteine proteinase similar to E-64 but E-64-c was 100 to 1000 times stronger than EST in in vitro cathepsin inhibition. However, EST was stronger than E-64-c in cathepsin inhibition when given orally. The cathepsin B&L activities (whole activities of cathepsins B and L) in the skeletal muscle, heart and liver of hamsters were strongly inhibited soon after oral administration of 100 mg/kg body weight of EST. The inhibition continued for at least 3 h and then disappeared gradually. E-64-c was found in plasma of hamster treated with EST, but unchanged EST was not found. These results suggested that EST was converted to E-64-c, a more active form, during the permeation through intestinal membrane. The conversion of EST to E-64-c was also indicated by the absorption experiment using in situ loop method. EST was thus shown to be useful as an oral drug and expected to be effective in therapeutic trials using model animals.