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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 487 records · Page 27Linked to original sources

Purification and comparative characterization of cytochrome P-450scc from porcine adrenocortical mitochondria.

Cytochrome P-450scc (cholesterol side-chain cleavage enzyme) was purified from porcine adrenocortical mitochondria. 2. The purified cytochrome P-450scc was found to be homogeneous on SDS-polyacrylamide gel electrophoresis. 3. The heme content of the purified enzyme was 20.6 nmol/mg protein. 4. The enzymatic activity of the reconstituted cytochrome P-450scc-linked monooxygenase system amounted to 7.8 nmol of pregnenolone formed per nmole of P-450 per minute, with cholesterol as a substrate. 5. The amino acid sequence of the amino-terminal region of the cytochrome P-450scc and the amino acid residue at the carboxyl terminal were determined and compared with those of other mammalian cytochromes P-450scc.

Adrenal Cortex↗

The differences in 12-hydroxyeicosatetraenoic acid and thromboxane B2 release from guinea pig platelets.

Anti-12(S)-hydroxyeicosatetraenoic acid (12-HETE)-antibody and anti-thromboxane B2 (TXB2)-antibody were generated and applied to the radioimmunoassay. The detection limit for 12-HETE was 16 pg. The cross-reactivities of anti-12-HETE-antibody were 4.6% for 15-HETE, 0.18% for 5-HETE and below 0.15% for leukotrienes and prostaglandins (PGs). 12-HETE and TXB2 released from guinea pig platelets were measured by radioimmunoassay. Platelet activating factor (PAF) at 10(-9) M induced the aggregation of platelets, the releases of immunoreactive-12-HETE (1.8 +/- 1.2 ng/10(8) platelets, mean +/- S.D.) and immunoreactive-TXB2 (18.5 +/- 17.3 ng/10(8) platelets). Collagen at 1 microgram/ml also evoked platelet aggregation, the releases of immunoreactive-12-HETE (2.7 +/- 1.1 ng/10(8) platelets) and immunoreactive-TXB2 (11.8 +/- 4.6 ng/10(8) platelets). By the stimulation with these compounds, TXB2 was produced in a greater amount than 12-HETE from guinea pig platelets. Although 10(-7) M and 10(-6) M U46619, a TXA2 mimetic, caused platelet aggregation, arachidonic acid metabolites were not released. These data suggest the presence of different mechanisms of platelet activation depending on each stimulus.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Catalytic properties of cytochrome P-450scc from bovine and porcine adrenocortical mitochondria: effect of Tween20 concentration.

Cholesterol side-chain cleavage activities of cytochrome P-450ssc purified from bovine adrenocortical mitochondria were measured for various substrates, including cholesterol, 20[S]-hydroxycholesterol, 22[R]-hydroxycholesterol and 20[R], 22[R]-dihydroxycholesterol, in the reconstituted enzyme system at various Tween20 concentrations. The side-chain cleavage activity for cholesterol showed more than 10-fold enhancement upon addition of 0.1% Tween20, compared with that without the detergent. Addition of Tween20 did not cause any enhancement of the side-chain cleavage activities for 20[S]-hydroxycholesterol and 22[R]-hydroxycholesterol; rather, it resulted in an inhibition of the activities. The side-chain cleavage activity for 20[R],22[R]-dihydroxycholesterol showed a very high value even without the detergent. As the stimulatory effect of Tween20 was only specific for cholesterol, Tween20 seemed to enhance the rate of access of cholesterol to cytochrome P-450scc. These results are consistent with the suggestion that a transfer of substrate, cholesterol, in mitochondrial inner membrane, to the substrate-binding site of cytochrome P-450scc is the rate-limiting step in the cholesterol side-chain cleavage reaction.

Adrenal Cortex↗

The effects of anticonvulsant drugs on vitamin D3-activating cytochrome P-450-linked monooxygenase systems.

The effects of two anticonvulsant drugs, phenytoin and sodium valproate, on the bioactivation of vitamin D3 have been studied with respect to the microsomal and mitochondrial cytochrome P-450-linked monooxygenase systems that contribute to 25-hydroxylation of vitamin D3 in rabbit liver, and the mitochondrial cytochrome P-450-linked monooxygenase system that catalyzes 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in rabbit kidney. These anticonvulsant drugs were found to inhibit the 25-hydroxylase activity on vitamin D3 in liver microsomes and mitochondria, respectively, but not to inhibit the 1 alpha-hydroxylation of 25-hydroxyvitamin D3, even over a wide concentration range. Moreover, the activities of the components of the cytochrome P-450-linked monooxygenase systems: NADPH-cytochrome P-450 reductase, NADPH-ferredoxin reductase and ferredoxin, were never inhibited by these drugs. It is possible that the inhibition of bioactivation of vitamin D3 by these anticonvulsant drugs causes rickets and osteomalacia, and the site of inhibition is expected to be the cytochrome P-450 mediated reactions in liver mitochondria.

Animals↗

Age-related changes of J-chain-positive cells in chickens.

Localizations of J-chain-positive cells (JPC) were examined in chicken lymphatic tissues before and after hatching. The cells containing J chain were first detected in medullary areas of the bursa of FABRICIUS during the embryonic stage. These positive cells were partly detected in the developing small lymphatic follicles: perhaps on newly differentiating precursor B-cells. In addition to these lymphatic follicles, connective tissue of bursal fold were also detected as J-chain positive. Although similar localizations of JPC were again observed in hatched chickens, positive areas of follicular medulla were strongly stained for fluorescence with corresponding antisera than that of embryonic ones. These data may reflect differences in the physiology of lymphocytes in respect to functional development. JPC localizations were next compared between the B-cell subpopulations, mu-(microPC) and alpha-chain-positive cells (alpha PC). The J-chains detectable in the IgM molecules were also found in follicular medulla. However, these follicles were almost found to be negative for J-chains detectable in the alpha PC before hatching. Any strong stainings for J-chain in the alpha PC were, moreover, not be observed in bursa after hatching. The microPC localizations in hatched chickens were roughly equal with the pattern of JPC localization. These analyses revealed the presence of the cells having the chains of both mu and J. The results together with other recent studies further shown that bursal J-chain can be partly detected in newly differentiated lymphatic follicles lacking IgM-producing and suggest the possible presence of B-cell-differentiation sequence of Ig-J+----IgM+J+----IgA+J+.

Aging↗

Effect of gomisin A in the prevention of acute hepatic failure induction.

Nearly all rats develop massive hepatic cell necrosis and die upon intravenous administration of heat-killed Propionibacterium acnes followed by a small amount of Gram-negative lipopolysaccharide 7 days later. However, when such an experimental liver disorder is induced in rats raised for 4 or more weeks on food containing 0.06% of gomisin A extracted and purified from Schizandra chinensis, the survival rate rises, histological changes of the liver improve remarkably, and splenocyte reactivity to phytohemagglutinin and pokeweed mitogen as well as splenocyte interleukin 1 productivity are retained. These results suggested the possibility that the development of acute hepatic failure may be prevented with the oral administration of gomisin A.

Animals↗

Separation of the prodigiosin-localizing crude vesicles which retain the activity of protease and nuclease in Serratia marcescens.

Crude vesicles in which prodigiosin is localized were separated from pigmented Serratia marcescens. The bacteria were grown on peptone-glycerol agar plate, suspended in saline, and fractionated into cells, vesicles, and supernatant by differential centrifugation. Electron microscopic observations showed that the fractionation was conducted properly and the separated vesicles were lysed in distilled water. The vesicles suspended in saline retained 100 kilodalton protein of which amount is correlated with prodigiosin level, but the 100 kDa protein was found in the supernatant when the vesicles were lysed in distilled water. The vesicle fraction retained few colony-forming units and little detectable activity of NADH oxidase, but showed much higher activities of protease and nuclease than the cell fraction. The profiles of the activities of the protease and the nuclease in the fractions were different from each other, that is, the protease activity in the vesicle fraction was lower than that in the supernatant fraction, whereas the nuclease activity in the vesicle fraction was higher than that in the supernatant fraction, suggesting that the two extracellular enzymes were released from the pigmented bacteria by different mechanisms.

Cell Fractionation↗

Recognition of MHC TL gene products by gamma delta T cells.

We have studied the ligand specificity of a gamma delta T-cell receptor (TCR) derived from a mouse T-cell hybridoma (KN6). KN6 cells reacted with syngeneic (C57BL/6) cells from various origins (splenocytes, thymocytes, peritoneal exudate cells, etc.) and cells from many different mouse strains. KN6 reactivity against cells from a panel of congenic and recombinant mouse strains demonstrated that the ligand recognized by KN6 is controlled by an MHC-linked gene that most probably maps in the TL region. We cloned this gene and formally proved that it does map in the TL region. This gene turned out to be a novel class I gene (designated T22b) belonging to a hitherto unidentified cluster of TL region genes in strain C57BL/6. This gene was expressed in many different tissues and cell types. We also examined the tissue expression of several other TL genes. One of these, the structural gene (T3b) encoding the thymus leukemia (TL) antigen from C57BL/6 mice, was specifically expressed in the epithelium of the small intestine. Since the intestinal epithelium of the mouse is known to be the homing site for a subset of gamma delta T cells (i-IEL) bearing diverse TCR with V7 rearranged gamma chains, we propose that the T3b gene product is part of the ligand recognized by some of the i-IEL. Our data support the idea that gamma delta T cells might be specific for non-classical class I or class I-like molecules and suggest that gamma delta TCR and non-classical MHC co-evolved for the recognition of a conserved set of endogenous or foreign peptides.

Age Factors↗

[A mechanism of usefulness of treatment with erythromycin for diffuse panbronchiolitis].

The clinical usefulness of treatment with erythromycin for diffuse panbronchiolitis (DPB) patients have been well reported to date, although its mechanisms remain unknown. In a previous study, we demonstrated that DPB patients were found to have large percentages of neutrophils in their lower respiratory tracts and suggested that neutrophils play an important role in the pathogenesis of DPB (Chest 99: 917-923, 1990). While in vitro and in vivo studies have demonstrated that erythromycin decreases neutrophils directed migration. In the present study, we performed bronchoalveolar lavage (BAL) on eight patients with DPB to clarify the cell populations in the lower respiratory tract before and after treatment with erythromycin. Neutrophils percentages in BAL fluid were significantly reduced after treatment with erythromycin (54.3 +/- 22.4% to 13.1 +/- 13.5%, p less than 0.01). No significant variance of BAL lymphocyte percentages was demonstrated after treatment with erythromycin. These results suggest that a main mechanism of clinical usefulness of treatment with erythromycin for DPB may be inhibition of neutrophils migration into the lower respiratory tract instead of intrapulmonary bactericidal activity against organisms.

Adolescent↗

[A case of Cushing's syndrome associated with Nocardia cerebral abscess].

A 58-year-old woman was admitted to our hospital with complaints of general fatigue, thirst and lumbago. A diagnosis of Cushing's syndrome was made on the basis of elevated serum levels of cortisol and adrenocorticotropic hormone (ACTH). Although Cushing's disease was most suspected, no evident image of pituitary adenoma could be found on brain CT scan and MRI. Therefore, treatment with oral Trilostane was started. Three months after admission, left hemiplegia was noticed and cerebral abscess in the right frontal lobe was demonstrated by brain CT scan. In spite of surgical removal of the abscess by total resection, she had a relapse in the same site and also developed a new lesion in the left lateral lobe. Surgical drainage was performed and Nocardia asteroides was isolated from the drained pus. An intensive chemotherapy with aminobenzylpenicillin (ABPC) and latamoxef (LMOX) in combination resulted in marked decrease in size of the lesion in the brain and subsequent improvement of left hemiplegia was achieved. Since approximately one month before when a diagnosis of cerebral abscess was made, there had been demonstrated a coin lesion in the right middle field on chest X-ray films. This lesion in the right lung disappeared concomitantly with the improvement of the lesions in the brain. This fact strongly suggests that the lesion in both brain and lung were of the same nature. Nocardia is known to make a primary lesion in the lung after being inhaled and then through hematogenous dissemination to make distant lesions in various sites, especially in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Abscess↗

[A case of mediastinal abscess due to Enterococcus faecalis accompanied with superior vena cava syndrome].

Superior vena cava (SVC) syndrome caused by benign diseases is rare. We reported a case of mediastinal abscess due to Enterococcus faecalis (E. faecalis) accompanied with SVC syndrome and reviewed the literature on this particular condition. A 38-year-old female with swelling of the neck and dilatation of cervical vein was admitted to our hospital, being diagnosed as having a SVC syndrome. Chest roentgenogram revealed an enlargement of the right upper mediastinum and a massive infiltration in the right upper lung field. CT scan demonstrated a mass with central necrosis occupying the right upper mediastinum and stenosis of superior vena cava. Further conformation of the stenosis of vena cava was made by means of venography. E. faecalis was recovered from the pus aspirated from the mediastinal abscess, and a definitive diagnosis of SVC syndrome caused by mediastinal abscess due to E. faecalis was made. There has been no report, to our knowledge, on mediastinal abscess evolving SVC syndrome in which E. faecalis was identified as a causative organism. The present case indicates that a benign disease such as lung abscess should be considered to be a possible cause of SVC syndrome in addition to other frequent malignant diseases.

Abscess↗

[Role of transiently accumulated neutrophils in the lung of hamster in development of pneumonia due to Mycoplasma pneumoniae].

The importance of Mycoplasma pneumoniae as a pathogen of human infectious diseases, particularly of respiratory infections, has been well recognized. However, the details of the mechanism through which lung tissue damages are produced in mycoplasmal infection has not been fully understood. It has been pointed out that beside the direct invasive process certain immunological responses to the deposited microbes are crucial in development of mycoplasmal pneumonia. In the present study, we aimed at elucidating the role of neutrophils in producing pneumonia due to Mycoplasma pneumoniae in hamsters. For this purpose, hamsters were divided into two groups; the one not pretreated and infected with Mycoplasma pneumoniae and the other immunosuppressed by 60Co irradiation and infected. A serial determination of the numbers of mycoplasmal cells recovered from the treacheal tissue and bronchoalveolar lavage fluid (BALF) and analysis of cellular components in BALFs were carried out. The severity and the nature of pathological changes produced in the lungs were evaluated and scored on the basis of microscopic findings. As a result, it was found that the numbers of mycoplasmal cells recovered from both tracheal tissues and BALFs reached maximum on the seventh day of infection in both groups and decreased rapidly. There no apparent difference was found between the two groups in number of cells recovered. In the not-irradiated control groups, the percentage of polymorphonuclear leukocytes (PMNs) in BALF was very high on the seventh day and then they were replaced by lymphocytes by the 21st day of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Elastase activity in bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis].

The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.

Adolescent↗

Effects of hachimijiogan on dopamine, serotonin and vasoactive intestinal peptide in plasma and hypothalamus in sulpiride-induced hyperprolactinemic rats.

Effect of Hachimijiogan (HJ) on dopamine (DA), serotonin (5-HT) and vasoactive intestinal peptide (VIP) was examined in plasma and hypothalamic tissue of sulpiride-induced hyperprolactinemic rats (SHR). Similar to bromocriptine (BR), HJ, in combination with sulpiride, suppressed plasma prolactin levels raised by sulpiride alone. Furthermore, HJ, together with sulpiride, increased plasma DA levels decreased by sulpiride alone, while 5-HT in plasma was increased by sulpiride and HJ, individually or in combination. However, plasma VIP levels were under detection limits on some occasions after HJ treatment. Successively, DA, 5-HT and VIP levels in the hypothalamus were determined. Similar to the effect caused by BR, DA and 5-HT levels in hypothalamic tissue reduced by sulpiride alone were also significantly increased by HJ together with sulpiride, while VIP levels were sometimes under detection levels with or without HJ. These results suggest that HJ stimulates the hypothalamus to increase DA and 5-HT in SHR, providing evidence for the clinical efficiency of HJ in combating hyperprolactinemia. The effect of HJ on VIP in plasma or hypothalamic tissue is, however, questionable.

Animals↗

Thermoluminescence dosimetry of gamma rays using ceramic samples from Hiroshima and Nagasaki: a comparison with DS86 estimates.

This study reports gamma-ray doses measured using thermoluminescence (TL) dosimetry of atomic-bomb-exposed ceramic samples from Hiroshima and Nagasaki. Advances in the dosimetry of TL-sensitive minerals in the field of TL dating of archaeological and geological materials made it possible to measure a radiation dose of 10(-2) Gy. Ceramic samples such as tiles and bricks were collected from locations between 523 and 2,453 m from the hypocenter in Hiroshima and from between 731 and 1,565 m in Nagasaki. The gamma-ray dose estimates derived from these samples are compared with estimates from DS86. A significant discrepancy was noted between the doses measured for samples from Hiroshima and DS86 values. One possible cause of this discrepancy might be a secondary gamma-ray dose related to the neutron dose.

Ceramics↗

Subcutaneous and mediastinal emphysema associated with hypersensitivity pneumonitis.

We report a rare case of a patient in whom severe subcutaneous and mediastinal emphysema occurred in association with summer-type hypersensitivity pneumonitis and in whom overdistention or disruption of alveoli with obliteration of the respiratory bronchioles was revealed on open lung biopsy. This case suggests that obstructive bronchiolitis with hypersensitivity pneumonitis is an etiologic factor of mediastinal emphysema.

Adult↗

An 82 year-old patient with sarcoidosis.

An 82 year-old woman presented with bilateral uveitis suggestive of ocular sarcoidosis, which led to a clouded vision. She was diagnosed as having sarcoidosis because of an elevated level of serum angiotensin converting enzyme (ACE), findings from a Ga67 scintiscan and the bilateral uveitis, although her chest X-ray film was normal. This patient is one of the most oldest patients on record to have sarcoidosis.

Age Factors↗