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Biomedical subjects

K Komori

Publications and source records attributed to K Komori.

At least 19 recordsLinked to original sources

Semiquantitative analysis of immunoreactivities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the locus coeruleus of desipramine-treated mice.

The influence of antidepressant drugs on catecholaminergic neuron groups of the mouse brain was studied immunohistochemically, using a microphotometric semiquantitative method. The immunoreactive level of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in the locus coeruleus (LC) was significantly decreased after 2 weeks of antidepressant administration. Our results suggest that long-term exposure to an antidepressant drug, desipramine, significantly affects intracellular catecholamine-synthesizing enzymes. These results may suggest some significant roles of the catecholaminergic neuronal groups to the action of the tricyclic antidepressant drugs.

Animals

High aortic occlusion associated with lupus anti-coagulant.

Lupus anti-coagulant (LAC) has been recognised in association with venous and arterial thrombotic events. We retrospectively investigated the relationship between LAC and 21 patients with juxtarenal high aortic occlusion. Four of the 21 patients were LAC positive (19%), one of whom was a woman suffering from systemic lupus erythematosus (SLE). The three men had neither SLE nor any other connective tissue disease. The mean age of the four patients was 43.5 years and three of them (75%) were younger than 50 years of age. By contrast, the mean age of the 17 patients without LAC was 59.9 years and 14 of them (82.4%) were older than 50 years. The postoperative courses in all four patients with LAC undergoing arterial reconstructions were uneventful. Two patients were treated by either anti-coagulation or anti-platelet agents, postoperatively. The present paper demonstrates for the first time that, in patients with juxtarenal high aortic occlusion, the incidence of LAC positivity is higher in younger patients (below 50) than in older patients (above 50). In addition, our results show that a preoperative evaluation of the presence of LAC is required in cases with juxtarenal high aortic occlusion, particularly when the partial thromboplastin time (PTT) is prolonged and the patients are younger than 50 years old.

Adult

The potential risk for subclavian vein occlusion in patients on haemodialysis.

Subclavian vein (SCV) stenosis or occlusion can be a late complication of temporary haemodialysis or following catheterisation for intravenous hyperalimentation. In five patients with prior catheterisation or trauma of the SCV, incapacitating oedema of the upper extremity developed only after the creation of ipsilateral arteriovenous (AV) fistulas for haemodialysis. The duration of the previous catheterisation was 2 to 4 weeks. Massive upper extremity oedema developed at 10 days to 22 months with an average of 11 months after the establishment of AV fistulas. Subclavian-axillary vein bypass using a ringed polytetrafluoroethylene graft was successful for one patient and ligation of the AV fistulae led to good results for the other three. In planning vascular access procedures in the upper extremity, venography should be mandatory to try to prevent such complications if a previous history of subclavian catheterisation exits.

Aged

Simultaneous resection of abdominal aortic aneurysms and early gastric cancer by retroperitoneal and transperitoneal approach.

The surgical approach to patients with abdominal aortic aneurysm and gastrointestinal malignancy remains controversial. We experienced two cases with abdominal aortic aneurysm and gastric cancer, which were treated by a one-stage operation using a different approach. At first, the operation for the aneurysm was done through a retroperitoneal approach and then, a partial gastrectomy for gastric cancer was done through a transperitoneal approach. The postoperative course of both cases was uneventful. The patients were discharge on the 19th and 21st postoperative days, respectively. This one-stage operation using different isolated approaches, such as the retroperitoneal approach for abdominal aortic aneurysm and transperitoneal approach for gastric cancer, was useful for the patients with abdominal aortic aneurysm and particularly early gastric cancer in terms of preventing an infection of the prosthetic graft.

Adenocarcinoma

Possible role of cytomegalovirus in the pathogenesis of inflammatory aortic diseases: a preliminary report.

To search for possible evidence of a relationship between human cytomegalovirus and aortic diseases, we examined 41 aortic lesions excised at surgery and 16 aortic tissues obtained at autopsy for the presence of cytomegalovirus DNA, by use of polymerase chain reaction. Cytomegalovirus DNA was present in seven (88%) of eight lesions of inflammatory aortic diseases with periaortic fibrosis, five of six inflammatory aneurysms, and all of two aortic occlusive lesions with inflammation. Cytomegalovirus DNA was detected in 20 (61%) of 33 atherosclerotic aneurysms, whereas it was detected in only five (31%) of 16 autopsy samples that showed neither inflammation nor atherosclerosis. Thus the possibility that cytomegalovirus may play a role in the pathogenesis of inflammatory aortic diseases warrants further attention.

Adult

Phosphorylation of the rodent negative acute-phase protein alpha 1-inhibitor-III by the insulin receptor tyrosine kinase.

alpha 1-Inhibitor-III (alpha 1I3), a broad range proteinase inhibitor, member of the alpha-macroglobulin family, is abundant in normal rat plasma. Insulin-dependent tyrosine phosphorylation of a monomeric 195K glycoprotein (pp195) was observed in wheatgerm agglutinin (WGA)-Sepharose-purified insulin receptor preparations from rat liver and muscle. Phosphorylation of pp195 in vitro required a basic poly-amino acid, i.e. poly-L-lysine. We present evidence identifying pp195 as alpha 1I3. In situ perfusion with saline essentially removed pp195 from rat livers. Addition of normal rat plasma to liver homogenates or to WGA eluates restored insulin-stimulated phosphorylation of pp195; plasma from streptozotocin-diabetic rats was much less effective. Liver-derived pp195 copurified with an abundant plasma protein, with the characteristics of alpha 1I3, on size exclusion and ion-exchange chromatography. An approximately 195K protein, comigrating with alpha 1I3, was markedly diminished in plasma from diabetic rats, and alpha 1I3 concentration was decreased by approximately 70% upon immunoblot analysis. Highly purified alpha 1I3 was phosphorylated by muscle- or liver-derived insulin receptors in the presence of 1 microM poly-L-lysine and comigrated with pp195 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. alpha 1I3 phosphorylation was half-maximal at approximately 70 nM and was stimulated by insulin 7-fold. Hindlimb perfusion removed more than 90% plasma albumin but only approximately 20% pp195 from muscles. alpha 1I3 messenger RNA was identified in liver but not in muscle. A specific antibody against alpha 1I3 immunoprecipitated phosphorylated pp195 in WGA-purified insulin receptor preparations from nonperfused liver and from saline perfused and nonperfused muscle. alpha 1I3 is bound and internalized by alpha-macroglobulin receptors; whether it is phosphorylated in vivo is unknown. Hepatic alpha 1I3 synthesis may diminish in diabetic rats.

Acute-Phase Proteins

A rare case of extramedullary plasmacytoma in the mediastinum.

A rare case of extramedullary plasmacytoma in the mediastinum is reported. An 80-year-old man was admitted for further examination of a mediastinal tumor. Chest computed tomography (CT) revealed a large mediastinal mass and right interlobar pleural effusion. Needle biopsy under CT guidance established a diagnosis of plasmacytoma. Immunohistochemical staining revealed that the tumor cells were producing monoclonal IgA kappa. Serum immunoelectrophoresis revealed an IgA kappa monoclonal component with a serum concentration of 5,040 mg/ml. The bone marrow aspiration was normal. Bone roentgenogram and bone scintigram showed osteoporosis but no neoplastic lesion.

Aged

[Tumor associated carbohydrate antigens in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis].

It is known that tumor associated carbohydrate antigens are significantly increased in the serum of patients with diffuse panbronchiolitis (DPB). We investigated carbohydrate antigens (SLX, CA19-9) in bronchoalveolar lavage fluid (BALF) obtained from 24 patients with DPB. The concentrations of SLX and CA19-9 were significantly higher in BALF from patients with DPB than those from healthy subjects (7 cases) and patients with pulmonary sarcoidosis (16 cases). No significant correlation was observed between either SLX or CA19-9 concentrations in the serum and BALF, and no significant correlation was observed between the concentrations of these carbohydrate antigens in BALF and clinical findings. Immunohistochemical study of SLX and CA19-9 in open lung biopsy specimens obtained from patients with DPB showed expression of SLX and CA19-9 on the bronchiolar surface epithelial cells and mucinous exudates in air spances. These results indicate that carbohydrate antigens are presumably increased in the pulmonary lesions of patients with DPB, and this increase causes high levels of these antigens in the serum. Furthermore, we investigated the change of concentrations of SLX and CA19-9 in BALF obtained from patients with DPB after erythromycin (EM) treatment. The concentrations of these two antigens were decreased after EM treatment.

Adolescent

[A clinical study of the long-term therapeutic effects of low-dose erythromycin in diffuse panbronchiolitis--with special reference to changes in tumor-associated carbohydrate antigens in serum].

We investigated the long-term (3-30 months) therapeutic effects of low-dose (300-600 mg/day) erythromycin in 26 patients with diffuse panbronchiolitis (DPB). Significant improvements of pulmonary functions especially in %VC and PaO2 as well as respiratory symptoms were shown. However, erythromycin treatment was not associated with a significant change in surface phenotypes on peripheral blood lymphocytes (CD4, CD8, CD4/CD8). It is well known that serum levels of tumor-associated carbohydrate antigens such as SLX (sialylated Lewis X-i) and CA19-9 (sialylated Lewis(a)) are significantly elevated in patients with DPB. In the present study, 68.4% (13/19) of DPB patients showed marked elevation of SLX and 52.9% (9/17) showed marked elevation of CA19-9 levels in serum. These positive ratios were significantly decreased by erythromycin treatment to 31.6% (6/19) in SLX and 23.4% (4/17) in CA19-9. The mean values of each marker were also significantly decreased after erythromycin administration from 54.9 +/- 26.9 U/ml to 39.5 +/- 22.1 U/ml for SLX and from 70.5 +/- 77.4 U/ml to 28.8 +/- 37.4 U/ml for CA19-9.

Adolescent

[A 14-year-old with pulmonary hamartomatous lymphangiomyomatosis associated with bilateral pneumothoraces].

A 14-year-old girl was admitted because of cough, chest pain and hemosputum. Chest roentgenogram on admission showed a pneumothorax and a cavitary lesion with niveau formation in the right lung and cystic lesions in the bilateral lung fields. After bed rest and intravenous administration of antibiotics for two weeks, the right lung inflated well and the niveau formation disappeared, and the patient was discharged. One week later, she was readmitted with sudden-onset severe dyspnea, caused by bilateral pneumothoraces. Emergency tube thoracostomy and wedge resection of the bullous lesion was performed. Macroscopically, multiple small cystic changes were seen on the surface of the right lung. Histological examination revealed nodular proliferations of smooth muscle cells in the interstitium and vessel walls in the lung, which contained slit-like lymphatic channels. The diagnosis of pulmonary lymphangiomyomatosis was made. In this case, we could not measure receptors for estrogen and progesterone. Recently, hormonal therapy and oophorectomy have been reported as being useful. Tamoxifen (Norvadex) was therefore initiated, and the patient has remained well with slight dyspnea on exertion. There has been no recurrence of pneumothorax. Lymphangiomyomatosis is a rare disease of unknown etiology which occurs exclusively in women, mostly in those of reproductive age. We report a 14-year-old female patient with lymphangiomyomatosis associated with repeated pneumothorax, who had been under treatment for epilepsy. We believe this case to be of importance because of the long discussed relation between pulmonary lymphangiomyomatosis and tuberous sclerosis.

Adolescent

Do some tyrosine hydroxylase-immunoreactive neurons in the human ventrolateral arcuate nucleus and globus pallidus produce only L-dopa?

The presence of 'tyrosine hydroxylase (TH)-only'-immunoreactive (IR) neurons is reported for the first time in the human hypothalamic region and basa ganglia, using immunohistochemical technique. 'TH-only'-IR neurons were demonstrated in the ventrolateral part of the arcuate nucleus and medial segment of globus pallidus. These neurons lacked aromatic L-amino acid decarboxylase (AADC)-, dopamine-beta-hydroxylase (DBH)-, and dopamine (DA)-immunoreactivity. The above results suggest that these 'TH-only'-IR neurons are not dopaminergic, and possibly contain L-DOPA as an end-product.

Arcuate Nucleus of Hypothalamus

Endothelium-derived relaxing factor and vein grafts.

Platelet thrombosis, intimal hyperplasia and progression of atherosclerosis are the most important factors determining the patency of vein grafts for arterial occlusive disease. Interactions between aggregating platelets and the vessel wall play an important role in all of these processes. Recently, it has become evident that the endothelium modulates the underlying vascular smooth muscle by releasing an endothelium-derived relaxing factor, a potent vasodilator and anti-aggregating substance. Little information is available, however, on such endothelial functions of autogenous vein grafts. This review focuses on vascular modulation by endothelium-derived relaxing factor in vein grafts.

Adenosine Diphosphate

[A study of bronchoalveolar lavage analysis in patients with diffuse panbronchiolitis--the results of low dose and long term erythromycin treatment].

Cellular analysis including lymphocyte surface markers in BALF in 17 patients with DPB (14 male; 36 female) was performed. The total number of cells increased remarkably, especially the percentage of neutrophils (72.9 +/- 14.1%). On the contrary the percentage of alveolar macrophage decreased (15.4 +/- 8.9%). The CD4/CD8 ratio in DPB was also significantly decreased to 0.73 +/- 0.38% when compared with normal healthy nonsmokers. Five patients with low dose and long term EM treatment were analyzed. Total cell counts as well as the neutrophil percentage (7.3 +/- 4.0%) decreased significantly. On the other hand the percentage of alveolar macrophage increased to 76.6 +/- 0.6%, which was almost similar to those obtained from normal healthy volunteers. Therefore it is concluded that both clinical and BALF findings improved concordantly after EM treatment.

Adult

Increased hepatic insulin proreceptor-to-receptor ratio in diabetes: a possible processing defect.

Hepatic insulin proreceptors and receptors were studied in control and in ketotic diabetic rats 2-4 wk after streptozotocin treatment. Solubilized preparations were partially purified by wheat germ agglutinin-agarose (WGA) and lentil lectin agarose (LLA) chromatography to enrich eluates in insulin receptors and proreceptors, respectively. After phosphorylation with [gamma-32P]ATP, an approximately 190-kDa glycoprotein was identified in LLA eluates as the insulin proreceptor, based on insulin dose-dependent tyrosine autophosphorylation, immunoprecipitation with insulin receptor-specific antibodies, and high-mannose glycosylation. Mature approximately 95 kDa phosphorylated beta-subunits were present in both LLA and WGA eluates. LLA also showed phosphorylated partially processed beta-subunits (approximately 85 kDa) and proreceptors (approximately 190 kDa). Proreceptors comprised less than 1% of the total yield of hepatic insulin receptors. The incorporation of 32P into proreceptors (per gram liver or DNA) was 4.7- or 4.5-fold greater in diabetic vs. control rats, whereas receptor labeling increased only 1.8- or 1.5-fold in diabetic rats. beta-Subunit autophosphorylation per receptor was identical in control and diabetic rats. The phosphorylation data suggested a diabetes-associated 2.6-fold increase in proreceptor-to-receptor ratios. When assessed by cross-linking with 125I-labeled insulin or by immunoblotting, proreceptor-to-receptor ratios were increased 1.5- and 3.1-fold, respectively, in diabetic rats. The data suggest that uncontrolled diabetes may alter insulin receptor processing.

Animals

Diabetes-associated impairment of hepatic insulin receptor tyrosine kinase activity: a study of mechanisms.

Insulin receptor tyrosine kinase activity solubilized from liver of control and streptozotocin diabetic rats was studied using histone H2b and poly-Glu-Tyr (4:1) as phosphoacceptors. Both substrates inhibited autophosphorylation and exogenous kinase activity when added before, but not after, receptor activation with ATP. When H2b was added before ATP, insulin stimulated exogenous kinase activity of diabetic-derived receptors was significantly higher (approximately 50%) than control values at low H2b concentrations, but significantly lower (approximately 50%) than control values at high H2b concentrations, suggesting a decrease in the apparent Km and maximal velocity of the diabetic receptor tyrosine kinase toward H2b. When receptors were allowed to maximally autophosphorylate before the addition of H2b, the maximal H2b kinase activity of diabetic-derived receptors was only approximately 25% lower than that of controls. These effects were not attributable to altered ATP kinetics. Insulin receptor kinase activity toward the substrate poly-Glu-Tyr (4:1) was unaltered by insulinopenic diabetes. Insulin receptor alpha-beta dimers were not detectable in either control or diabetic-derived preparations. We conclude that the impairment of hepatic insulin receptor kinase activity associated with insulinopenic diabetes reflects a decreased ability to maximally activate, which is enhanced when the receptor is activated in the presence of some substrates, e.g. H2b. Impaired signalling by the diabetic-derived receptor appears to be dependent on the type of substrate and its concentration.

Adenosine Triphosphate

Skeletal muscle insulin-receptor kinase. Effects of substrate inhibition and diabetes.

Insulin receptor tyrosine kinase activity solubilized from hind limb muscle of control and streptozocin-induced diabetic (STZ-D) rats (2-3 wk) was studied with the substrates histone H2B and poly glutamic acid-tyrosine (glu-tyr) (4:1). Basal and insulin-stimulated kinase activities were inhibited when high concentrations of either substrate were added before initiation of phosphorylation with ATP. Under these conditions, insulin-stimulated activities of diabetic- and control-derived receptor kinase toward H2B were similar at 0.008 mg/ml H2B. However, higher concentrations of H2B (0.04-1 mg/ml) progressively reduced the ratios of diabetic-derived to control-derived receptor kinase activities to approximately 0.5. When inhibition of receptor kinase activities was prevented by allowing maximal autophosphorylation of insulin receptors before addition of H2B, kinase activity of diabetic- and control-derived receptors was similar at all H2B concentrations. Diabetic-derived insulin-receptor tyrosine kinase activity toward poly glu-tyr (4:1) was not significantly different from that of control rats. Under conditions of substrate inhibition (0.4 mg/ml H2B), insulin receptor H2B kinase activity from muscles of rats with severe diabetes (85 mg/kg STZ, 7 days) was significantly decreased, whereas the same activity from rats with moderate diabetes (50 mg/kg STZ, 7 days) was not significantly different from control rats. Insulin receptor alpha,beta dimers were not detectable in muscle preparations from control or diabetic rats. The data suggest that the impairment of muscle-derived insulin-receptor tyrosine kinase activity associated with insulinopenic diabetes reflects, in part, enhanced inhibition by some substrates. If solubilized insulin receptors and the exogenous substrates studied model in vivo events, impaired signaling of the muscle insulin receptor in insulinopenic diabetes may depend on the type and concentration of intracellular tyrosine kinase substrates and the severity of the metabolic derangements.

Animals

The impairment of endothelium-dependent relaxations in reversed vein grafts is associated with a reduced production of cyclic guanosine monophosphate.

The present study investigated the underlying mechanisms associated with the loss of responsiveness of veins grafted into the arterial circulation. In particular, the possibility that the altered response is related to modifications of the biologic properties of the vascular smooth muscle, of the endothelial cells or both was tested. Segments of jugular veins were grafted in the reverse position into the carotid arteries in rabbits. After 4 weeks the patent vein grafts and unoperated veins were removed, and endothelium-dependent (acetylcholine) and endothelium-independent (nitric oxide, SIN-1 [the active metabolite of molsidomine32]) relaxations were studied in vitro. In unoperated veins, acetylcholine, nitric oxide, and SIN-1 induced a concentration-dependent relaxation in the presence and absence of the endothelium, respectively. These relaxations were associated with a time-dependent accumulation of guanosine 3':5'-cyclic monophosphate (cyclic GMP). Both relaxation and production of cyclic GMP were inhibited by methylene blue and hemoglobin. Unstimulated veins with endothelium had a significantly higher content of cyclic GMP than did preparations without endothelial cells. This difference was abolished by hemoglobin and methylene blue. In vein grafts acetylcholine induced only minor endothelium-dependent relaxations, whereas nitric oxide and SIN-1 evoked concentration-dependent relaxations in preparations without endothelium, which were shifted significantly to the right compared to unoperated veins. In vein grafts the endothelium-mediated production of cyclic GMP (basal and stimulated by acetylcholine) was significantly reduced when compared to that in unoperated veins, and that evoked by SIN-1 was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

[Two cases of interstitial pneumonitis with marked increase of tumor-associated carbohydrate antigens in serum].

Tumor-associated carbohydrate antigens, CA19-9 and SLEX have been used clinically as markers for malignancy. However, it is also known that these antigens are frequently elevated in the serum of patients with benign lung diseases. We have experienced two cases of interstitial pneumonitis with marked increase of carbohydrate antigens in serum, the level of which changed according to their clinical course. Case 1. A 64-year-old woman was admitted because of a cough and exertional dyspnea. Despite treatment with various antibiotics and prednisolone, she died of respiratory failure approximately two months after admission. Her CA19-9 and SLEX in serum elevated from 500 U/ml to 5506 U/ml and 167 U/ml to 1187 U/ml respectively in accordance with clinical deterioration. Autopsy revealed no malignancy. Case 2. A 57-year-old woman, who had been suffering from interstitial pneumonitis associated with rheumatoid arthritis, was admitted with a cough and fever. She responded to prednisolone therapy, however two years later she readmitted because of exacerbation and died of respiratory failure. The initial CA19-9 level in serum was 876 U/ml and dropped to 42 U/ml with prednisolone therapy. The serum antigen level again increased during the period of exacerbation, and showed 133 U/ml immediately before death. An immunohistochemical study of CA19-9 and SLEX in various tissues obtained by autopsy was performed in case 1. The distribution of these antigens in tissue was similar to that of normal individuals. The exceptions were the expression of these antigens on epithelial cells of microscopic honeycombing and on mucinous exudates in air spaces.

Antigens, Tumor-Associated, Carbohydrate