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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 361 records · Page 20Linked to original sources

Invasive thymoma with hypogammaglobulinemia spreading within the bronchial lumen.

A case of invasive thymoma with hypogammaglobulinemia showing endobronchial growth is presented. A 63-year-old man was admitted for evaluation of a left hilar mass. A biopsy specimen obtained from the intraluminal mass, which occluded the left upper division bronchus, was highly suggestive of thymoma. The laboratory tests were almost normal except for hypogammaglobulinemia. The tumor was resected with the left upper lobe. Most of the tumor invaded the left upper lobe, and grew into the bronchi. The case was diagnosed histologically as invasive thymoma spreading within the bronchial lumen.

Agammaglobulinemia↗

Eosinophil activation in patients with pulmonary fibrosis.

The eosinophil count and concentrations of eosinophil cationic protein (ECP) were measured in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), sarcoidosis, and healthy controls. The patients with IPF and PF-CVD showed significant increased eosinophil count and ECP levels in BALF compared with the controls. When the patients with IPF and PF-CVD were subclassified into chronic stable, progressive, and acute progressive subgroups in accordance with the observed progression of pulmonary dysfunction during the preceding 3- to 6-month period, those in the acute progressive subgroup showed significantly elevated recovered eosinophil count and ECP level, as well as recovered lymphocyte count and total protein, albumin, and type III procollagen aminoterminal peptide-related antigens (pIIIp) in BALF, compared with either of the other two subgroups. Multivariate stepwise logistic regression analysis revealed that, among these variables, only ECP and pIIIp significantly contributed to discrimination among the three subgroups differing in disease activity. These findings suggest that eosinophils are involved in the inflammatory process in pulmonary fibrosis and that the released ECP and other cytotoxic eosinophil products may contribute to the lung injury and development of fibrosis.

Adult↗

IL-5 predominant in bronchoalveolar lavage fluid and peripheral blood in a patient with acute eosinophilic pneumonia.

We describe an acute eosinophilic pneumonia (AEP) patient with bronchoalveolar lavage fluid (BALF). Eosinophil cell number (47%), content of interleukin (IL)-5 (8.22 x 10(2) pg/ml) and eosinophil cationic protein (9.25 micrograms/ml) were high in BALF. No eosinophilia was seen in peripheral blood on admission; however, content of IL-5 was 9.47 x 10(2) pg/ml. After methylprednisolone pulse therapy, he improved rapidly with a reduction in eosinophil cell number (7%) and the content of IL-5 (< 100 pg/ml) in BALF. However, a high content of IL-5 (6.9 x 10(2) pg/ml) and transient eosinophilia (17.5%) were seen in peripheral blood. It is important to distinguish between AEP and infectious pneumonia, because of the differing treatments. If the diagnosis of AEP is doubtful, BALF should be performed early.

Acute Disease↗

Effects of ranitidine on gastric vesicles containing H+,K(+)-adenosine triphosphatase in rats.

BACKGROUND: To ascertain the mechanism for rebound acid hypersecretion after treatment with an H2-receptor blocker, we investigated the effects of ranitidine on gastric H+,K(+)-adenosine triphosphatase (ATPase) in rats. METHODS: Male Wistar rats received ranitidine (1-50 mg/kg body weight intraperitoneally twice a day for 5 days). The rats were starved for 15 h after the last treatment and then killed, and gastric vesicles containing H+,K(+)-ATPase were prepared. RESULTS: Treatment with ranitidine dose-dependently increased protein content in the gastric vesicular fraction purified from the gastric mucosa without changing total protein content. Ranitidine also increased the content of a 94,000-dalton protein, the catalytic subunit of H+,K(+)-ATPase. On the other hand, ranitidine did not affect the specific activity of the enzyme (mumol/min/mg of the gastric vesicular protein). Since gastric vesicles in the fasting state mainly consist of the tubulovesicular membrane, these results suggest that ranidine administration increases total tubulovesicular H+,K(+)-ATPase content (mumol/min/rat) by increasing the number of tubulovesicles per parietal cell. The ranitidine-induced increase in total tubulovesicular H+,K(+)-ATPase activity was still evident 1 week after treatment and returned to control level 1 month later. CONCLUSIONS: All these findings suggest that the increased content and total activity of tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H2-blocker therapy.

Animals↗

[A trial of antegrade perfusion to the lower half of the body with selective cerebral perfusion for repair of aortic arch aneurysm combined with atherosclerosis obliterance].

A 73-year-old man with aortic arch aneurysm combined with atherosclerosis obliterance underwent aortic arch replacement. As he had bilateral femoral artery obstruction, we instituted ECC with arterial perfusion through the ascending aorta. Then, the left ventricle started dilating due to mild degree of aortic regurgitation. So with selective cerebral perfusion, we perfused the lower half of the body through a Foley balloon catheter which was inserted from the aortic arch antegradely. We could perfuse with the catheter for 20 minutes for core cooling and then during repair until the catheter disturbed the operation. The Foley catheter had given us some difficulties for handling during the procedure. Based on this experience, we have made a catheter which had both a balloon for aortic occlusion and a tube for perfusion and which we could keep away from operative fields, similar to the way we used antegradely insertable aortic occlusion balloon catheter.

Aged↗

[Treatment of patients with chronic dissecting aortic aneurysm (DeBakey type IIIb) presenting with compromised renal perfusion].

We reviewed our experience for 6 patients of chronic dissecting aortic aneurysm (DeBakey type IIIb) with the false lumen extending into the abdominal aorta and the renal arteries being perfused from the false lumen. In three cases, whose abdominal aorta presenting with large aneurysmal lesions, we performed graft replacement of the thoracic descending aorta and abdominal aorta simultaneously. In other three cases, whose abdominal aorta presenting without aneurysmal lesions, and moreover age advanced or perioperative conditions poor, we performed graft replacement of thoracic descending aorta, using double barreled distal anastomosis technique to ensure of enough blood flow into both true and false lumens. All patients survived and there were no early postoperative complications. In 3 cases of thoracic aortic replacement alone, the mean follow-up term was 38 months, postoperative computed tomography showed neither apparent expansion of the false lumen nor compression of the true lumen of the abdominal aorta, and postoperative renal function were maintained. In conclusion, in treatment of chronic dissecting aortic aneurysm (DeBakey type IIIb) presenting with compromised renal perfusion, we considered that replacement of the thoracic descending aorta and abdominal aorta brings patient the most radical improvements. But in the patients, who are elder or in poor perioperative conditions, the replacement of thoracic descending aorta using double barreled distal anastomosis technique is one easier applicable and safer procedure to preserve the renal perfusion.

Adult↗

[A case of chronic pancreatitis with eosinophilic pleural effusion].

A 48-year-old man was admitted for the evaluation of a massive left pleural effusion. Thoracenthesis yielded a bloody excudate with a high percentage of eosinophils (27%) and high values of pancreatic enzymes (amylase 16,000 Somogyi, Elastase 35,000 ng/dl, Lipase 12,800 U/l, Trypsin 77,000 ng/ml). The amylase isozyme of the exudate was 100% pancreatic-type fraction. The blood showed no eosinophilia (4%). A computed tomographic scan and magnetic resonance image of the abdomen revealed a pancreatic pseudocyst in contact with the diaphragm, and thrombi in the inferior vena cava and the splenic vein. After pancreatic cystectomy and splenectomy, the pleural effusion resolved rapidly. Eosinophilic pleural effusion has been reported as a complication of several disorders: pneumonia, lung carcinoma, pulmonary tuberculosis, and pulmonary infarction. However, we know of no previous report of eosinophilic pleural effusion with pancreatitis. In this case, it is interesting that the massive eosinophilic pleural effusion associated with chronic pancreatitis resolved immediately after the operation, and the patient was discharged.

Chronic Disease↗

Application of 198Au grains for carcinoma of oral cavity.

PURPOSE: The purpose of this study is to analyze the results of the treatment using gold grain implants over the past 9 years and to evaluate the usefulness of this treatment method. PATIENTS AND METHODS: From January 1985 through April 1993, a total of 45 patients with squamous cell carcinomas of the oral cavity and the oropharynx were treated with 198Au grain (gold grain) at the Department of Radiology, Osaka University Medical School. The initial activity of the grains supplied weekly by the Japan Radioisotope Association was usually 5 mCi (185 MBq), and single implants were usual. In case of combined external irradiation, telecobalt gamma-rays or 4 MV X-rays were used for treatment before implant. RESULTS: The local control rate for patients with T1 stages was 80% (20/25) and with T2 stages, 59% (10/17). The local control rate was 71% (10/14) for gold grain alone and 72% (13/18) for external irradiation combined with gold grain implants (combined therapy). In combined therapy, the median of the interval between external irradiation and gold grain implants was 21 days. The treatment interval for patients with recurrent diseases was 22 days, 22, 27, 39 and 46, respectively. The progression rate showed a tendency to increase in the patients with longer interval (more than 21 days), and with partial regression after external irradiation (p = 0.0085). CONCLUSION: Our findings show that the time interval between external irradiation and gold grain implantation is an important factor in combined therapy. Therefore, we emphasize that the time interval should be shorter than 3 weeks.

Adult↗

Continuing immunoglobulin heavy chain gene rearrangements in chronic myeloid leukemia with recurrent B-lymphoid blast crises after bone marrow transplantation.

We sequentially analyzed the immunoglobulin heavy chain variable (IgH V) region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blot analysis using the JH probe showed different rearranged bands at each crisis, although the same rearranged bands of the BCR gene were observed. We amplified and sequenced the IgH V region gene of the leukemia cells by reverse transcriptase polymerase chain reaction (RT-PCR) using the primers corresponding to the consensus 5'VH and mu constant regions. The dominant leukemia clone at each crisis had a unique VH-D-JH rearrangement; VH4A (V79)-DLR2-J5 (clone-1), VH4B (DP70)-DK4-J6 (clone-2) and VH4A (V79)-DN4-J6 (clone-3) at the first, second and third crises, respectively. Further analysis by PCR amplification using the consensus 5'VH and clone-specific primers revealed that clone-1 underwent VH4-->VH3 replacement at the second crisis, and that clone-3 was already in existence at the first crisis. Moreover, the DN4-J6 joining clone, in which the sequence was the same as that of clone-3, was identified at the first and third crises by PCR amplification using primers corresponding to the region upstream of the DN4 segment and DN4-J6 boundary of clone-3. These observations suggest that multiple clones were generated from the progenitor cells of blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny, by continuing rearrangement mechanisms of the IgH genes, and that the dominant clone at each crisis was undergoing change.

Adult↗

[Septic lung caused by methicillin-resistant Staphylococcus epidermidis].

A 55-year-old man was admitted to our department one month after resection of rectal carcinoma, with complaints of fever and general malaise. Shock developed rapidly after admission. The chest X-ray film and computed tomography showed diffuse small nodular shadows and bilateral pleural effusion. Septic lung caused by Methicillin-resistant Staphylococcus epidermidis (MRSE) was diagnosed from the results of a bacteriological study. This bacteria is a Coagulase Negative Staphylococcus (CNS). Chemotherapy with Minocycline and Cefotiam was effective. Characteristic radiologic features of this case may be related to the early stage of adult respiratory distress syndrome (ARDS) and septic pulmonary microembolism.

Anti-Bacterial Agents↗

[Acute lung injury and chemical mediators].

The essential abnormality in acute lung injury is an increase in pulmonary permeability. The mechanisms involved are complex, and may include direct effects on endothelial cells; the actions of neutrophils, macrophages, and lymphocytes; and chemical mediators generated by these cells. Neutrophils are known to be important in acute lung injury, and the mediators they produce, especially protease and oxidants, may be responsible for endothelial cell injury. We studied the roles of neutrophil elastase and oxygen radicals in acute lung injury by Escherichia coli endotoxin in sheep with lung lymph fistulae. The results of these and other studies indicate that these substances are related to the increase in pulmonary permeability during the late phase of injury.

Acute Disease↗

[Diagnostic imagings and embolotherapy for the superior mesenteric vein-inferior vena cava shunt].

Diagnostic imaging and embolization therapy for the uncommon portal and mesenteric vein-inferior vena cava shunt (PV.SMV-IVC shunt) are reported. As the frequency of clinical symptoms such as hematemesis, melena and confusion caused by gastrointestinal varices, or hepatoencephalopathy was about 40%, it was important for this disease entity to be diagnosed with noninvasive diagnostic images. The careful examination of the area around the right renal vein was able to overcome the low diagnostic rate of 20-40% obtained with US and CT images. In cases of simple PV.SMV-IVC shunt without gastrointestinal varices, embolization therapy using steel coils and done by the intravenous approach is easy and noninvasive. On the other hand, in cases of complex PV-SMV-IVC shunt with gastrointestinal varices, dual balloon occluded embolization therapy using a liquid sclerosing agent and done by the intravenous and portal approaches is preferable.

Adult↗

Glial extracellular matrix modulates gamma-glutamyl transpeptidase activity in cultured bovine brain capillary and bovine aortic endothelial cells.

Glial extracellular matrix (ECM) elevated gamma-glutamyl transpeptidase (gamma-GTP) activity in cultured bovine brain capillary and aortic endothelial cells (BBCEC, BAEC). In particular, the ECM of glial cells cultured with the conditioned medium of BAEC (BAEC CM) dramatically elevated gamma-GTP activity in BBCEC and BAEC. The ECM of glial cells cultured with BBCEC CM also had a marked effect. The ECM of 3T3 cells cultured with BAEC CM, and the ECM of glial cells cultured with 3T3 CM had no effect. Glial CM had no effect on gamma-GTP activity in BBCEC and BAEC. These findings indicate that gamma-GTP activity in endothelial cells (EC) is modulated by glial ECM, and that the factor of ECM that affects gamma-GTP activity in EC arises from the interaction between glial cells and EC.

Animals↗

Results of combined external irradiation and chemotherapy of bleomycin or peplomycin for squamous cell carcinomas of the lower gingiva.

PURPOSE: In Japan, the role of radiotherapy for gingival carcinomas has not been considered as a radical treatment, but only a pre and/or postoperative treatment. This study was aimed to discuss a possibility of radiotherapy for a radical treatment. In this study, radiotherapy was given as an initial treatment for squamous cell carcinomas of the lower gingiva in simultaneous combination with chemotherapy of bleomycin or peplomycin (Tokyo, Japan). METHODS AND MATERIALS: When complete regression of the tumor was obtained, subsequent surgery was postponed with or without a booster of radiotherapy of about 30 Gy until a recurrent lesion was confirmed. RESULTS: Sixty-seven percent of 100 patients with T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or T4 had complete regression. The 5-year local control rate by T classification, including the results of secondary treatments (surgery and/or radiotherapy and/or chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and 61% for T4. The 5-year local control rate according to treatment methods was 95% in the group without surgery and 86% in the group with surgery for T1 and T2 patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage II, 71% for Stage III, 51% for Stage IV and 70% overall. CONCLUSION: The combination of radiotherapy and chemotherapy could be a conservative radical treatment for T1 and T2 patients with lower gingival carcinoma.

Bleomycin↗

Cyclic hexapeptide endothelin receptor antagonists highly potent for both receptor subtypes ETA and ETB.

A cyclic hexapeptide, cyclo(-D-Asp-Trp-Asp-D-Leu-Leu-D-Trp-), designed from cyclo(-D-Glu-Ala-D-alloisoleucyl-Leu-D-Trp-), an ETA receptor-selective antagonist, possessed not only affinity similar to that of BQ-123 for ETA but also higher affinity for ETB than BQ-123. Further modification led to the discovery of cyclo(-D-Asp-Asp(Php)-Asp-D-Thg-Leu-D-Trp-) (Asp(Php): 1-beta-aspartyl-4-phenylpiperazine; Thg: 2-(2-thienyl)glycine) that inhibited [125I]ET-1 binding to the ETA and ETB receptors with IC50 values of 0.082 nM and 120 nM, respectively. Although this compound possesses 1470-fold less affinity for ETB than for ETA, it behaves as a non-selective antagonist that equipotently inhibits vasoconstriction mediated by both receptor subtypes ETA and ETB.

Amino Acid Sequence↗

Inhibitors of acyl-CoA:cholesterol acyltransferase. 1. Synthesis and hypocholesterolemic activity of dibenz[b,e]oxepin-11-carboxanilides.

A series of N-phenyl-6,11-dihydrodibenz[b,e]oxepin-11-carboxamides and related derivatives were prepared on the basis of structures of the reported inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). These compounds were tested for their ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters in vivo. The structure-activity relationships in vitro were as follows. Substitution at positions 2 and 6 in the anilide resulted in potent inhibitory activity, and the potency increased with increasing size of the substituents, with maximum potency being obtained with a 2,6-diisopropyl substitution. The position of the substituent on the dibenz[b,e]oxepin ring system influenced the activity, and substitution at position 2 was critical for potent activity. The electronic effect of the substituent at position 2 does not influence activity, but bulkiness seems to be a significant factor. The lipophilicity of the compounds also plays an important role in determining ACAT inhibitory activity. Among the compounds tested, 2-bromo-N-(2,6-diisopropylphenyl)-6,11-dihydrodibenz-[b,e]++ +oxepin-11- carboxamide (33, KF17828) showed significant in vitro activity (rabbit liver microsomes IC50 = 23 nM) and the most potent in vivo activity (complete reduction in elevated serum total cholesterol levels at a dose of 10 mg/kg in hamsters).

Animals↗

The loop sequence plays crucial roles for isomerization of intramolecular DNA triplexes in supercoiled plasmids.

The effect of base composition in the central region of polypurine.polypyrimidine (Pur.Pyr) tracts on the formation of intramolecular DNA triplexes in plasmids was examined using chemical probes (diethyl pyrocarbonate and OsO4), and two-dimensional (2-D) agarose gel electrophoresis. Two isomers exist for an intramolecular triplex: one with the 3'-half of the Pyr strand as the third strand (H-y3) and the other with the 5'-half of the Pyr strand as the third strand (H-y5). It was shown that the content and position of G + C residues in the triplex loop region (the center of Pur.Pyr tracts) are primary determinants for the isomerization between the H-y3 and H-y5 triplexes. Divalent metal ions such as Mg2+ and negative supercoiling also modulate the isomerization: the H-y5 conformation is stabilized by the divalent metal ions and/or under relatively lower negative supercoiling. 2-D gel analyses revealed that two isomers, H-y3 and H-y5, are topologically non-equivalent: the H-y3 formation relaxes one more supercoil turn than H-y5. As the G + C content in the center of Pur.Pyr tracts increases, the triplex requires more supercoil energy for formation. Therefore, the base-pair opening in the center of Pur.Pyr tracts is the initial and critical step in the pathway for the formation of triplex as well as the isomerization. The role of the triplex loop sequence is explained by a model in which the nucleation process of H-y3 formation requires a wide range of base-pair opening compared to that of H-y5: such unwinding would not be favored for the central region of the duplex with high G + C content and so it would be in the presence of Mg2+, and thereby the H-y5 formation is promoted.

Base Composition↗

Effects of a new endothelin antagonist, TAK-044, on post-ischemic acute renal failure in rats.

Protective effects of a new endothelin (ET) receptor antagonist, TAK-044, were studied in a model of acute renal failure (ARF) in rats. ARF was induced by clamping the left renal pedicle for 45 minutes with contralateral nephrectomy and subsequent reperfusion of the left kidney. Plasma creatinine concentration (Pcr) increased to 2.28 mg/dl 24 hours after reperfusion of the ischemic kidney. Intravenous administration of TAK-044 (1-10mg/kg) prior to renal occlusion dose-dependently but partially attenuated the increase in Pcr and the morphological damages of the kidney. ET-1 and ET-3 increased perfusion pressure in isolated kidney preparations with similar potency, indicating that the renal vasoconstriction evoked by these ET isomers is mainly via ETB receptors, and TAK-044 (10nM) shifted the ET-1 dose-response curve to the right by a factor about 10. In a rat renal membrane fraction, ET-1 showed competitive inhibition of specific [125I]ET-1 binding with an IC50 value of 0.34nM and a Hill slope of 1.10. ET-3 did so with a higher IC50 value (3.3nM) and a lower Hill slope (0.56), suggesting that rat kidney contains both ETA and another receptor subtype, probably ETB. TAK-044 inhibited ET-1 binding with an IC50 value of 6.6nM and a Hill slope of 0.41. Plasma concentrations of immunoreactive TAK-044 were maintained over 7nM for 8 hours following i.v. injection of 10mg/kg TAK-044. These results suggest that endogenous ET is involved in the pathogenesis of post-ischemic ARF, at least, in part and that TAK-044 provided protective effects against ARF by blocking ET receptors, possibly both ETA and ETB receptors in renal vasculature and parenchymal cells.

Acute Kidney Injury↗