[A case of pregnancy with insulin autoimmune syndrome].
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Adult↗
Biomedical subjects
K Takagi
Publications and source records attributed to K Takagi.
Neonatal changes of osteoclasts in osteopetrosis (op/op) mice defective in production of functional macrophage colony-stimulating factor (M-CSF) protein and effects of M-CSF on osteoclast development and differentiation.
In mice homozygous for the osteopetrosis (op) mutation, loss of osteoclasts in the postnatal period and their development, differentiation, and maturation following daily M-CSF administration in adult life were investigated. Histochemical, immunohistochemical, and ultrastructural approaches, as well as [3H]thymidine autoradiography, clarified the role of M-CSF on osteoclast development and differentiation. In op/op mice osteoclasts appeared normal at birth. However, osteoclast numbers were reduced within a few days after birth, and osteoclasts were undetectable by 3-4 days of age. In adult op/op mice there were no multinuclear osteoclasts; however, small numbers of mononuclear cells (so-called 'preosteoclasts') were observed on the endosteal surface of bone. These preosteoclasts expressed tartrate-resistant acid phosphatase and showed ultrastructural features of immature osteoclasts. After daily M-CSF administration in op/op mice, osteoclasts developed from the fusion of preosteoclasts and osteoclasts numbers increased to the levels of normal littermates at 3 days. Autoradiographic analysis with [3H]thymidine revealed no labeling in osteoclasts and preosteoclasts. In the mutant mice, M-CSF administration induced numerical increases of monocytes, promonocytes, and earlier precursor cells in bone marrow, ER-MP12- or, ER-MP58-positive granulocyte/macrophage colony-forming cells (GM-CFCs). Among these macrophage precursors, ER-MP58-positive cells were considered preosteoclast precursors, and possessed marked proliferative potential. These data suggest that an ER-MP58-positive cell subpopulation of GM-CFCs proliferates in response to M-CSF, differentiates into preosteoclasts which fuse with each other to develop into mature osteoclasts.
Animals↗
Lobectomy by video-assisted thoracic surgery for a hilar bronchial carcinoid tumor.
A 45-year-old man with bronchial carcinoid arising from the subsegmental middle-lobe bronchus was treated by video-assisted thoracic surgery. Lobectomy with mediastinal and hilar lymph node sampling was successfully performed in this patient. To obtain a tumor-free surgical margin on the middle-lobe bronchus, the interlobar pulmonary artery was retracted posteriorly, the middle-lobe bronchus anteriorly. The bronchus was then stapled and transected.
Bronchial Neoplasms↗
[Thromboxane A2 synthetase inhibitor in asthma therapy].
Thromboxane A2(TXA2), a platelet aggregator and vasoconstricter, has been implicated as a potential mediator of bronchial asthma. TXA2 induces potent contraction of airway smooth muscles and airway hyperresponsiveness. OKY-046 (ozagrel hydrochloride) is a specific inhibitor of TXA2 synthetase and a new antiasthmatic agent. In a phase III study ozagrel has shown significantly higher effect in ameliorating the asthma symptoms and reduced the dose of concomitant steroid therapy compared to azelastine hydrochloride. Both basical and clinical studies showed that TXA2 synthetase inhibitor is effective on airway hyperresponsiveness. In this review the role of TXA2 synthetase inhibitor in current asthma therapy, which is based on the Japanese guideline of allergic disorders, was discussed.
Asthma↗
[Rapidly progressing BOOP in a patient with positive anti-Jo-1 antibody: response to corticosteroid pulse and immunosuppressant therapy].
A 61-year-old woman was admitted to our hospital with a two week history of knee-joint pain, dry coughing and dyspnea on exertion. A chest roentgenogram revealed bilateral patchy and infiltrative shadows. Laboratory examination revealed high CK and aldolase levels. Although myositic symptoms were absent, the respiratory symptoms rapidly worsened and respiratory failure developed. An open-lung biopsy and a muscle biopsy were done. The open-lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP), but the muscle biopsy specimen revealed non-specific findings. After 4 weeks of intravenous intermittent high-dose corticosteroid therapy, 50mg of cyclophosphamide was given daily, along with 20mg of prednisolone on alternate days. There were marked clinical, physiological and roentgenographic improvements. A test for anti-Jo-1 antibody was positive, which suggested that this patients had pulmonary manifestations of polymyositis/dermatomyositis. Although BOOP can have an indolent course and a good prognosis, it may rapidly worsen and respiratory failure may develop, in which case it should be treated aggressively with a combination of intravenous high-dose corticosteroids and immunosuppressants.
Antibodies, Antinuclear↗
[Dynamics of uric acid metabolism in hyperuricemia].
This paper is a review of the studies on urate metabolism of gouty patients with hyperuricemia and normal healthy subjects, performed mainly in our laboratory. The pathogenesis of hyperuricemia consisted of overproduction and underexcretion, which can be estimated using the urate clearance test. Overproduction was defined as urinary urate excretion (Uua) higher than [0.030 Cua + 0.325] mg/kg/hr and underexcretion as urate clearance (Cua) lower than 6.1 ml/min. According to those criteria, hyperuricemia was classified into the 4 types of overproduction (12%), underexcretion (60%), combined (25%) and normal type (3%). Patients with overproduction had a tendency of lower serum urate level (Sua) than those with underexcretion, higher Uua than those with the normal control and lower Cua and creatinine clearance (Ccr) than those with the normal control. Patients with underexcretion had a tendency of higher Sua and lower Cua, Ccr and Cua/Ccr ratio than those with overproduction or normal control. Patients with the combined type had the highest Sua among the 4 types, and those with the normal type had the lowest Sua. These findings indicate that each subtype of hyperuricemia has characteristic features in the urate metabolism, which are valuable for better understanding and treatment of hyperuricemia in gouty patients.
Blood Proteins↗
[Effect of long-term treatment with an inhaled corticosteroid on bronchial hyper-responsiveness and clinical asthma in asthmatic subjects].
We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.
Anti-Asthmatic Agents↗
Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats.
BACKGROUND: Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. METHODS: On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. RESULTS: 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). CONCLUSION: The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.
Animals↗
Thermal-phonon resonance.
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Journal Article↗
Local hemodynamic changes during transient middle cerebral artery occlusion and recirculation in the rat: a [14C]iodoantipyrine autoradiographic study.
We evaluated acute alterations of local cerebral perfusion following 30 min of transient right proximal middle cerebral artery (MCA) clip-occlusion in the rat and following two intervals of postischemic reperfusion. Local cerebral blood flow (lCBF) was assessed by [14C]iodoantipyrine autoradiography. Brain temperature was controlled at 35.5-36.5 degrees C throughout the experiment. We measured lCBF in four groups of rats: (a) sham-operated controls (n = 5), (b) following 30 min MCA occlusion (n = 5), (c) following 30 min of MCA occlusion with 15-min reperfusion (n = 6) and (d) following 30 min of MCA with 120-min reperfusion (n = 6). lCBF was measured in seven regions of the ischemic and non-ischemic hemispheres. MCA occlusion induced an ipsilateral reduction of lCBF, which was most severe in the parietal cortex (8.4 +/- 4.0% of control, mean +/- S.D.), and dorsolateral caudoputamen (20.0 +/- 13.4% of control). lCBF in the non-ischemic hemisphere and in ipsilateral regions lying outside the MCA territory also decreased significantly. lCBF recovery was incomplete when assessed following only 15 min of reperfusion. Reperfusion of 120 min led to return of cortical CBF to control levels, but lCBF in the caudoputamen remained depressed (50-55% of control values). Caudoputaminal CBF and cortical CBF values were highly correlated with one another under normal and ischemic conditions, but this correlation was disrupted following reperfusion. On the basis of these results, we speculate that, if a means were found to enhance the early recovery of lCBF following transient ischemia, this might expand the therapeutic window of opportunity for the institution of other neuroprotective strategies.
Acute Disease↗
Arrest of cell growth by necdin, a nuclear protein expressed in postmitotic neurons.
Necdin is a 325 amino acid residue protein localized to the nuclei of postmitotic neurons, which withdraw permanently from the cell cycle. To examine whether necdin confers the postmitotic phenotype, necdin cDNA was stably transfected into NIH3T3 cells, in which the protein was conditionally expressed using a eukaryotic lac repressor-operator expression system. When the transfectants were induced to express ectopic necdin, cell growth was arrested without appreciable reduction in cell viability. The expressed necdin molecule was localized to the nuclei of the transfectants. These results suggest that necdin is a nuclear factor that governs the permanent arrest of cell growth of postmitotic neurons during development of the nervous systems of vertebrates.
3T3 Cells↗
Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo.
Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10 micrograms of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1 beta and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1 beta and IL-1Ra positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1 beta and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1 beta and IL-1Ra.
Animals↗
Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers.
Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.
Adult↗
Determination of total plasma homocysteine and related aminothiols by gas chromatography with flame photometric detection.
A selective and sensitive method for the determination of total homocysteine (Hcy) and related aminothiols, such as cysteine (Cys) and cysteinylglycine (CysGly), in plasma samples by gas chromatography (GC) has been developed. After reduction of the sample with sodium borohydride, the liberated Hcy and other aminothiols were converted to their N,S-diisopropoxycarbonyl methyl ester derivatives and measured by GC with flame photometric detection using a DB-17 capillary column. The calibration curves were linear over the range 0.5-10 nmol for Hcy and CysGly, and over the range 5-100 nmol for Cys, and the correlation coefficients were above 0.996. Using this method, total plasma Hcy, Cys and CysGly could be directly analysed without prior clean-up of the sample and without any interference from coexisting substances. Overall recoveries of Hcy and other aminothiols added to plasma samples were 95-106%. Analytical results for the determination of total plasma Hcy, Cys and CysGly from normal subjects are presented.
Adult↗
Role of TNF alpha, IL-1, and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy.
We examined the generation of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and IL-1 receptor antagonist (IL-1ra), and their role in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy. The leukocyte infiltration was largely mediated by both TNF alpha and IL-1 and could be divided into at least two phases: the early (within 3 hr) phase which was partly inhibited by anti-TNF alpha, but not by IL-1ra, and the late phase (4-12 hr) mediated by both TNF alpha and IL-1, and largely inhibited synergistically with anti-TNF alpha and IL-1ra. Endogenous IL-1ra may be responsible for the downregulation of the late phase of leukocyte infiltration in this type of inflammation. The increased vascular permeability was composed of two phases: immediate (15 min) and delayed (2 hr). The immediate permeability was inhibited by H1-antihistamine but was not affected by anti-TNF alpha, by IL-1ra, or by depletion of neutrophils. The delayed permeability was completely inhibited by either depletion of neutrophils or by anti-TNF alpha and was not affected by IL-1ra or antihistamine. Production of TNF alpha was maintained in the leukopenic rabbits. It would thus appear that the delayed permeability is mediated by a relatively early fraction of leukocyte infiltration initiated by TNF alpha; however, TNF alpha is not the direct mediator of this delayed permeability.
Animals↗
NMDA and non-NMDA receptors mediate taste afferent inputs to cortical taste neurons in rats.
Two main subclasses of ionotropic receptors for excitatory amino acids (EAAs), N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors, are involved in neurotransmission in the cortex of mammals. To examine whether EAAs are transmitters at the cortical taste area (CTA) in rats and to elucidate which types of the two ionotropic receptors operate at these synapses, we studied the effects of microiontophoretic administration of EAA antagonists on the responses of 64 taste cortical neurons to four basic taste stimuli in urethane-anesthetized rats. Both D-2-amino-5-phosphonovalerate (APV), a selective antagonist for NMDA receptors, and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a selective antagonist for non-NMDA receptors, suppressed most of the taste responses. The percentage of neurons suppressed by APV (70.3%) was almost the same as that suppressed by CNQX (64.1%). These suppressive effects were independent of the effects of background discharges during the prestimulus, water-rinsing period. The percentage of neurons suppressed by the antagonists did not differ between any pairs of taste stimuli. The number of neurons possessing both receptors was larger in the granular insular area (area GI), one of the two CTAs, than in the dysgranular insular area (area DI). In addition, taste responses were suppressed by CNQX or by both APV and CNQX in area GI in a significantly larger number of layer V neurons than in area DI. The present results indicate that normal excitatory transmission of taste afferents in the CTA in rats was mediated by both NMDA and non-NMDA receptors. The finding that a large fraction of neurons in the CTA in rats mediated taste information through NMDA receptors in normal transmission might be related to the higher potency of the plasticity observed in the CTA.
2-Amino-5-phosphonovalerate↗
Thoracoscopic resection of a solitary pulmonary lymphangioma: report of a case.
We present herein the rare case of a young man who was found to have a solitary tumor in the right upper lobe of his lung by a routine chest X-ray. The tumor was removed by thoracoscopic surgery, and pathological examinations confirmed the diagnosis of a primary lymphangioma of the lung. A brief review of the available literature on this extremely rare type of benign tumor follows the case report.
Adult↗
Gene rearrangement studies on lymphoma of the lung: report of a case.
We describe herein how true lymphoma of the lung was differentiated from pseudolymphoma in a 45-year-old woman presenting with pulmonary infiltrates. Although segmental resection revealed typical histologic findings of pseudolymphoma of the lung and immunohistochemical studies did not demonstrate a monoclonal proliferation, Southern blot analysis of the frozen tissue revealed rearrangements in the heavy and light chains of the immunoglobulin gene, with no T-cell receptor gene rearrangement suggestive of a lymphoproliferative disorder. These findings indicate that the identification of gene rearrangement may be utilized to distinguish between true lymphoma and pseudolymphoma.
Blotting, Southern↗