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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 361 records · Page 20Linked to original sources

A bronchofibroscopic analysis of the bronchial mucosa using a dye-scattering method for the detection of bronchial lesions.

A study was undertaken to evaluate the usefulness of a dye-scattering method for the analysis of bronchial lesions. After methylene blue was introduced through a cannula, the bronchial staining intensities seen by bronchofibroscopy were later compared with the histologic findings in 74 biopsied specimens of lesions taken from 20 patients with lung cancer and from 6 patients with bronchiectasis, 2 with a rheumatoid lung, and 2 with sarcoidosis. It was found that 86% (25 of 29) of the specimens that stained positively were malignant. Further, 4 specimens that manifested a false positive response to staining were either too small to be inspected histologically or showed necrosis. Of 27 specimens that were negative to staining, 89% (24 of 27) were revealed to be nonmalignant lesions. In this latter group the response of 3 specimens was false negative on histologic inspection, 2 showing cancer cells without surface infiltration. We thus conclude that this dye-scattering method is of great use in enabling the differentiation of nonmalignant mucosa from neoplastic lesions and the preoperative determination of the stage of a tumor.

Bronchi↗

Purification and characterization of cytochrome P450 from an isobutene-forming microorganism, Rhodotorula minuta.

A cytochrome P450 was purified from microsomes of Rhodotorula minuta. The optical spectrum of the purified cytochrome was characteristic of a low-spin ferric heme protein. Isovalerate caused a type I spectral change in it. The amino-terminal sequence of the cytochrome was different from those of other known microsomal cytochrome P450s. These results indicate that the cytochrome, which is tentatively named P450rm, is a novel species of cytochrome P450.

Alkenes↗

A large chondroitin sulfate proteoglycan has the characteristics of a general extracellular matrix component of adult brain.

Extracellular matrix (ECM) is a secreted extracellular network. Few components of adult brain ECM are known. We have identified a new, large chondroitin sulfate proteoglycan (T1 antigen) that acts like a general ECM protein of brain. First, it is present throughout the brain; second, it has the properties of an extracellular protein; and third, it is extracted only under denaturing conditions. Immunocytochemical localization of the T1 antigen by light microscope shows it to be present throughout the rat brain in both white and gray matter. The T1 antigen outlines Purkinje and other large cells. No antigenicity is seen inside these cells. Biochemical evidence suggests that the T1 antigen is extracellular rather than cytosolic or intravesicular. The T1 antigen is disulfide-linked to two other proteins. Disulfide bonds are found only in extracellular or intravesicular proteins, not in intracellular cytosolic proteins. Moreover, the T1 antigen is probably not intravesicular. Unlike intravesicular proteins, only a small amount of T1 antigen is solubilized by nondenaturing detergents. While nondenaturing detergents extract but a small amount of T1 antigen from rat brain, the majority is solubilized by denaturing conditions (6 M guanidine-HCl). This behavior is similar to that of ECM components in other tissues and is unlike that of membrane proteins, even those linked to the cytoskeleton. We hypothesize that the insolubility of the T1 antigen in brain is due to its presence in an extracellular aggregate. The T1 antigen is a proteoglycan with a highly glycosylated protein core of 300 kDa. It does not appear to be related to the large, heavily glycosylated chondroitin sulfate proteoglycans aggrecan and versican, which were discovered in non-neural tissues. Antibodies to a 15 residue peptide present in both aggrecan and versican do not react with the T1 antigen.

Aggrecans↗

[Peripheral polyneuropathy due to sarcoidosis in a patient with intrathoracic, ocular and skin lesions].

Sarcoidosis is a multisystem disorder of unknown etiology presenting most frequently with bilateral hilar lymphadenopathy (BHL), pulmonary infiltration, and ocular and skin lesions. Neurological manifestations are found in about 5% of patients with systemic sarcoidosis. We report the case of a 58-year-old woman with neurosarcoidosis manifesting as isolated, peripheral polyneuropathy. This is a rare neurological manifestation. Two years before admission, she was found to have an abnormal chest radiograph showing BHL, and pulmonary sarcoidosis was diagnosed by lung biopsy. Six months later, she noted facial erythematous lesions, and lupus pernio was confirmed by skin biopsy. Fifteen months before admission, she developed visual disturbance of the right eye caused by sarcoid-uveitis. Two months before admission, she complained of paresthesia and weakness of limbs. She was admitted for nerve-biopsy. Sural nerve biopsy revealed sarcoid granulomas in the epineurial space, periangitis and axonal degeneration. Neurologically, the diagnosis of mononeuritis multiplex without cranial nerve palsy was made. Treatment with 30 mg prednisolone daily was initiated, and neurological and extraneurological improvement was noticeable within two weeks of treatment. The dose was carefully lowered over several months.

Female↗

[Two cases of acute eosinophilic pneumonia with precipitating antibody against Trichosporon cutaneum and Trichoderma viride].

Two cases of acute eosinophilic pneumonia are described. The patients presented with an acute febrile illness, dry cough, severe hypoxemia and diffuse pulmonary infiltrates. Total cell count and the number of eosinophils were increased in bronchoalveolar lavage fluid. The TBLB specimen showed eosinophilic infiltration of alveolar walls and spaces. Precipitating antibodies against Trichosporon cutaneum and Trichoderma viride were noted in the patients' sera, and environmental provocation tests gave positive results. The clinical features of acute eosinophilic pneumonia resemble those of summer type hypersensitivity pneumonitis. From these results, we consider that there is a certain degree of overlap between the two diseases.

Adult↗

Prenatal detection of ischemic changes in the placenta of the growth-retarded fetus by Doppler flow velocimetry of the maternal uterine artery.

OBJECTIVE: To determine the relationships among the pregnancy outcomes of growth-retarded fetuses, Doppler flow velocimetry of the fetomaternal circulation, and pathologic changes in the placenta. METHODS: Forty-seven fetuses confirmed to be growth-retarded by ultrasonographic biometry were monitored during pregnancy in terms of the resistance indexes of the maternal uterine, fetal umbilical, and fetal middle cerebral arteries. After delivery, the placentas were examined for pathologic changes such as infarction and villous ischemia. RESULTS: Compared with 23 fetuses with nonischemic placentas, 24 growth-retarded fetuses whose placentas showed ischemic lesions were more frequently delivered preterm (P < .001) and by cesarean for fetal distress (P < .01), and they also had lower mean pH, higher carbon dioxide pressure, and lower oxygen pressure values (P < .05). Compared with the fetal umbilical and middle cerebral artery resistance indexes, the uterine artery resistance index showed the highest sensitivity (91.7%), specificity (78.3%), and positive predictive value (81.5%) for detecting placental ischemic changes. Linear discriminative analysis also showed that the uterine artery resistance index had the strongest correlation (P < .00001) with the placental ischemic changes. CONCLUSION: Ischemia of the placenta is associated with an adverse pregnancy outcome in growth-retarded fetuses. The placental ischemic changes can be detected using Doppler flow velocimetry. Measurement of the uterine artery resistance index might be useful for determining the clinical management of growth-retarded fetuses.

Adult↗

Retinoic acids inhibit activation-induced apoptosis in T cell hybridomas and thymocytes.

Apoptosis is induced in immature thymocytes and T cell hybridomas upon stimulation via the TCR/CD3 complex. This phenomenon appears to be related to negative selection of T cell clones in the thymus. In T cell hybridomas, it has been shown that glucocorticoids inhibit TCR/CD3-mediated apoptosis, whereas glucocorticoids alone induce apoptosis. All-trans-retinoic acid (RA) at 0.1 to 10 microM also inhibited TCR/CD3-mediated apoptosis assessed by DNA fragmentation and cytolysis, but RA alone hardly induced apoptosis. RA enhanced the effects of glucocorticoids to induce apoptosis and to inhibit TCR/CD3-mediated apoptosis. TCR/CD3-mediated stimulation can be mimicked by the combination of ionomycin, a calcium ionophore, and PMA, an activator of protein kinase C, and the combination-induced DNA fragmentation was also inhibited by RA. RA, however, failed to inhibit the combination-induced increase in intracellular Ca2+ concentration or the combination-induced translocation of protein kinase C from the cytosolic fraction to the particulate fraction. Time course studies of RA addition into the culture indicated that a 3- to 6-h delay in the addition of RA did not reduce its inhibitory effect on anti-CD3-induced DNA fragmentation. These results suggest that RA interferes with the apoptotic process at some point after its initiation stage. It has been suggested that negative selection involves not only TCR/CD3-mediated signals but also LFA-1-mediated signals. RA at 0.01 to 1 microM significantly inhibited the induction of thymocyte apoptosis by co-immobilized mAb to CD3 and LFA-1 molecules. RA by itself hardly induced apoptosis, but enhanced glucocorticoid-induced apoptosis. The results suggest that thymic selection might be influenced by RA at near-physiologic concentrations. The receptors of glucocorticoids and RA belong to the erbA oncogene-related steroid hormone receptor superfamily. Thyroid hormones and 1 alpha,25-dihydroxy vitamin D3, whose receptors also belong to the superfamily, failed to modulate apoptosis in both T cell hybridomas and thymocytes.

Animals↗

Determination of diphenylmethane antihistaminic drugs and their analogues in body fluids by gas chromatography with surface ionization detection.

Eleven diphenylmethane antihistaminic drugs and their analogues were tested for their detection by capillary gas chromatography (GC) with surface ionization detection (SID). The GC-SID response was highest for doxylamine, diphenhydramine and orphenadrine and lowest for terodiline, clemastine and pipethanate. The detection limits for drugs with the highest response were 2-5 pg (ca. 6-20 fmol) on-column (100-250 pg/ml of body fluid). The detection limits with GC-SID were 10-100 times higher than those with GC with nitrogen-phosphorus detection. A detailed procedure for the isolation of the antihistaminics from human whole blood and urine by the use of Sep-Pak C18 cartridges, prior to GC-SID, is also presented. The recoveries of the drugs (50 or 500 pmol), which had been added to 1 ml of body fluids, were > 60%. The baselines remained steady as the column temperature was increased and the background was clean, especially for whole blood extracts.

Benzhydryl Compounds↗

Sensitive determination of phenothiazines in body fluids by gas chromatography with surface ionization detection.

Fourteen phenothiazine derivatives were tested for their detection by gas chromatography (GC) with surface ionization detection (SID). The sensitivity of GC-SID was highest with trimeprazine and levomepromazine, which contain aliphatic tertiary amino side chains, and lowest with thiethylperazine and thioproperazine, which contain sulphur residues. Chlorpromazine, trimeprazine and promazine showed excellent linearity between the SID response and the drug amount in the range 0.25-3.0 pmol on-column. Their detection limits were as low as ca. 5-10 pg (15-30 fmol) on-column (250-500 pg per ml of body fluid). A detailed procedure for isolation of phenothiazines from human whole blood and urine using Sep-Pak C18 cartridges, before the GC with SID, is also presented. The recoveries of the drugs (100 pmol), which were added to 1 ml of whole blood or urine, were more than 79%. The baselines remained steady as the column temperature was increased.

Chromatography, Gas↗

Significance of multidisciplinary therapy for hepatocellular carcinoma.

The effect of multidisciplinary therapy for hepatocellular carcinoma (HCC) was evaluated in 121 resected cases. The 5-year survival was 100% for absolute curative resection (12 cases), 59.1% for relative curative resection (n = 37) and 10.9% for relative non-curative resection (n = 59). However, none of the patients survived for more than 3 years after absolute non-curative resection (n = 13). The non-recurrence in the preoperative TAE groups was different from that in non-TAE groups undergoing absolute and relative curative resection. The 1- and 3-year non-recurrence rates for relative non-curative resection were 92.3% and 53.8%, respectively, for the preoperative TAE group and 56.1% and 28.1%, respectively for the non-TAE group. These data show that preoperative TAE is effective in relative non-curative resection. Functional disturbances of the coagulation-fibrinolysis system in cirrhotic patients were improved after PSE. All patients undergoing hepatectomy after PSE had an uneventful postoperative course, including well-maintained function of the coagulation-fibrinolysis system and a decrease in splenic volume. At 1 year after hepatectomy, cirrhotic patients with critical liver function and poor coagulation-fibrinolysis showed appreciable hepatic regeneration. One patient died of hepatic failure 1 year after the operation. In recurrent HCC, the 1-, 2- and 3-year survival values after reresection were 100%, 75.0% and 25.0%, respectively. The respective values following TAE were 79.0%, 42.0% and 9.0%. Three cases of recurrent HCC were effectively treated, i.e., two patients achieved a partial response and one showed no change, by continuous intra-arterial infusion of 5-FU and lentinan with intermittent one-shot injections of epirubicin using a subcutaneous infusion pump. These three patients are alive at 1 year and 7 months, 1 year and 4 months and 6 months after the treatment, respectively.

Adult↗

Kanji word reading process analysed by positron emission tomography.

Positron emission tomography, involving the H2(15)O injection technique, was used to study changes in regional cerebral blood flow during Japanese kanji word reading. Three-times intrasubject averaging analysis revealed that the main cortical responses occurred in the bilateral (left-side dominant) posterior inferior temporal area for visual input. We believe the left posterior inferior temporal area processes highly complex morphological features of kanji. For language output, left-side dominant activation of the posterior inferior frontal gyrus and the basal ganglia was found.

Adult↗

Expression of a Maize Ubiquitin Gene Promoter-bar Chimeric Gene in Transgenic Rice Plants.

We have constructed a chimeric gene consisting of the promoter, first exon, and first intron of a maize ubiquitin gene (Ubi-1) and the coding sequence of the bar gene from Streptomyces hygroscopicus. This construct was transferred into rice (Oryza sativa L.) protoplasts via electroporation, and 10 plants were regenerated from calli that had been selected for resistance to exogenously supplied bialaphos. Transgenic plants grown in a greenhouse were resistant to both bialaphos and phosphinothricine at a dosage lethal to untransformed control plants. Evidence of stable integration of the transferred gene into the genome of the regenerated primary transformant plants was obtained from Southern blot analysis. In addition, northern blot analysis indicated expression and proper splicing of the maize ubiquitin gene first intron from the primary chimeric transcript in these transgenic rice plants, and western blot analysis and enzymic assays verified expression of the active bar gene product. Apparent mendelian segregation for bialaphos resistance in T(1) progeny of primary transformants was confirmed.

Journal Article↗

Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients. Final report.

Final results of the 5-year multicentric collaborative study on the long-term effects of bromocriptine in the patients with Parkinson's disease are reported. This prospective study started in May 1985 in order to see whether the early combination therapy with bromocriptine and levodopa is really superior to the levodopa monotherapy with regard to the late side effects of levodopa in the treatment of parkinsonian patients. Another project of the study was to see the therapeutic efficacy of bromocriptine monotherapy without concomitant use of levodopa. For these purposes, a total of 702 patients with Parkinson's disease were enrolled into three groups: Group 1 (n = 286) with bromocriptine monotherapy, Group 2A (n = 216) with early combination of bromocriptine and levodopa, and Group 2B (n = 200) with levodopa alone. At the end of the 5-year study, 48 patients in Group 1 (16.8%) were still continuing bromocriptine monotherapy with satisfactorily good therapeutic effects. About half (49.1%) of the Group 2A patients remained on the combined therapy, and the comparable number of the Group 2B patients (46.0%) were also kept on the initial mode of therapy, while 13.5% of the latter group with levodopa monotherapy needed bromocriptine to be added in order to assure the good therapeutic effects. Moreover, significant differences were seen between group 2A and Group 2B with regard to the incidence of wearing-off phenomenon and dyskinesias. Disappearance rate of dyskinesias which were present at the time of enrollment was significantly higher in Group 2A than in Group 2B. No significant difference was noted as to the incidence of untoward symptoms and the death rate among all three therapeutic groups. These results support the view that the early combination of bromocriptine with levodopa is superior to levodopa alone in the treatment of Parkinson's disease.

Activities of Daily Living↗

Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients: analysis on the maintenance and the change of the original mode of treatment.

A nation-wide collaborative study to evaluate the long-term effects of bromocriptine in patients with Parkinson's disease was completed as described in the accompanying paper. The present study analysed the same data by paying attention to a group of patients who maintained the original mode of therapy and to a group of patients who changed the mode of treatment by adding levodopa or bromocriptine to the original drug. Surprisingly, 48 among 286 patients in a group of bromocriptine monotherapy maintained the original mode of therapy. This group has particular features of a short duration of illness and a low grade of Hoehn-Yahr's scale. It is noteworthy that this group of patients did not show wearing-off phenomenon. The effects of additional bromocriptine to levodopa for a 5-year period were analysed by comparing two groups of combination therapy and levodopa alone therapy maintained for 5 years, with 106 and 92 patients, respectively. Results were essentially the same as those obtained from the accompanying paper, i.e., in general, treatment by combination with bromocriptine may be more suitable than treatment by levodopa alone. In order to find the best timing of the combination of levodopa and bromocriptine, results of 3 groups were compared, i.e. a group of patients who started with bromocriptine alone and later added with levodopa (82 patients), a group of patients who maintained the combination for 5 years (106 patients) and a group of patients who started with levodopa alone and later added bromocriptine (27 patients). The best results were obtained in the group of 5-year combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Accumulation of cis-diamminedichloroplatinum (II) and its analogues in sensitive and resistant human ovarian carcinoma cells.

Human ovarian carcinoma cell line (NOS2), established from a patient with serous cystadenocarcinoma of the ovary, has been exposed to a stepwise increase in cis-diamminedichloroplatinum (II) (CDDP) concentration to produce a CDDP-resistant cell line NOS2CR) as an experimental model for resistance to CDDP. NOS2CR cells showed a 7-fold resistance to CDDP and a lesser degree of cross-resistance to diammine (1,1-cyclobutanedicarboxylato)-platinum (II) (CBDCA) and (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) (DWA2114R). In the absence of CDDP, cross-resistance to DWA2114R was reduced to the original level by 2 months, although 83% resistance to CDDP remained up to 6 months. To investigate CDDP-resistant mechanisms, alterations in the intracellular accumulation of CDDP and analogues were assayed by atomic absorption. In both NOS2 and NOS2CR cells, accumulation of CDDP increased linearly with time and was concentration-dependent. NOS2CR cells demonstrated 71, 52 and 12% reduction in accumulation of CDDP, CBDCA, and DWA2114R, respectively. These reductions did not seem to be due to P-glycoprotein, because expression of multidrug-resistant 1 gene was not detected in either NOS2 or NOS2CR cells. These studies indicate that the mechanisms of resistance to CDDP and analogues in NOS2CR cells are related in the main to reduced intracellular accumulation of drugs. DWA2114R might be helpful to treat CDDP-resistant and recurrent tumors which were treated by CDDP.

Antineoplastic Agents↗

Study of bronchus-associated lymphoid tissue in patients with diffuse panbronchiolitis.

Bronchus-associated lymphoid tissue (BALT) is thought to affect local immunologic defense mechanisms. Studies of BALT, however, have mainly been focused on animals, and information detailing the BALT structure and functions in humans is scanty. Therefore, the purpose of this study is to clarify BALT morphology and immunologic findings in patients with diffuse panbronchiolitis (DPB) and compare them with BALT findings in animals. Thus, in 17 patients diagnosed with DPB, open-lung biopsy specimens were reviewed, and lymphoid follicles with a lymphoepithelium that was determined as BALT were identified in 12 patients. BALT was found mostly at bifurcations from nonrespiratory bronchioles to respiratory bronchioles. This lymphoepithelium was devoid of cilia and was diffusely infiltrated with CD4-positive (helper/inducer) T cells. The majority of T cells were confined to the parafollicular area with a predominance of helper T cells. Also, a few high endothelial venules were recognized in the parafollicular area. Further, in a follicular area situated in the center of the BALT, a number of sigM-positive cells were found to be heavily distributed, suggesting that this follicular area has the characteristics of a B cell zone equivalent to a germinal center of the peripheral lymph nodes. These observations are comparable with BALT findings in animals and suggest that BALT is at least partially related to the local immune response.

Adult↗