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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 469 records · Page 26Linked to original sources
PubMed1997

[Successful pulmonary thromboendarterectomy in a patient with chronic pulmonary thromboembolism].

A 63-year-old patient had been diagnosed with angina pectoris for 5 months and came to us complaining of progressive exertional dyspnea. Echo cardiography showed remarkable pulmonary hypertension and we were prompted to do cardiac catheterization. The catheterization showed the pressure of the main pulmonary artery (PA) as 84/14 (36) mmHg and PA angiography showed a massive embolus in the right main PA. Chest computed tomography and lung perfusion scintigraphy were also compatible with pulmonary embolism. The patient had been treated with anticoagulant for 1 month, but he was not doing well. We decided to remove the embolus surgically. In a median sternotomy, a cardiopulmonary bypass was established with ascending aortic and two caval cannulae. During cooling, the right PA was mobilized within the pericardial reflection. An incision was made in the right PA. An organized thrombus was located at the central PA and extended to the distal segmental PA. Thromboendarterectomy was carried out carefully. To obtain a better operative view, circulatory arrest was introduced intermittently. The left PA was opened and the organized thrombus, located at the bifurcation between the upper and lower branch, was removed. Post-operative PA angiography showed remaining thrombus in the right lower PA, but the pressure of the main PA fell to 27/12 (18) mmHg. Pulmonary thromboendarterectomy by median sternotomy with the aid of deep hypothermia and circulatory arrest was useful to remove the thrombus in the bilateral PA, and to obtain good hemodynamic and symptomatic results.

Endarterectomy↗
PubMed1997

Molecular defects of the coproporphyrinogen oxidase gene in hereditary coproporphyria.

Hereditary coproporphyria (HCP) is an acute hepatic porphyria, and is an autosomal dominant disorder but with a variable degree of clinical expression. Molecular cloning, sequencing and expression of the defective gene for coproporphyrinogen oxidase (CPO) in a patient with HCP were carried out. Enzyme assays revealed that CPO activity in EBV-transformed lymphoblastoid cells from the proband and one of her sisters was approximately 50% of normal. Nucleotide sequence analysis of CPO cDNAs isolated from the proband's cells demonstrated 3 base substitutions which accompanied 3 different amino acid substitutions. An A514-->C transition causing an Asn172-->His substitution occurred in one allele, while two other transitions, G265-->A and G580-->A, caused Gly89-->Ser and Val194-->Ile substitutions, respectively, in the other allele. The A514-->C and the G580-->A transitions were shown to be genetic polymorphisms. Transfection of CPO cDNA into E. coli demonstrated that cDNA with the G265-->A transition produced a protein with less than 5% of normal enzyme activity. These findings indicate that the G265-->A transition, involving the highly conserved glycine residue at the 89th position, is responsible for the CPO defect in the patient and accounts for the partial deficiency of CPO activity in this pedigree. This mutation is different from three other mutations reported in patients with HCP. Molecular defects in the porphyrias including HCP are highly heterogeneous.

Cell Line, Transformed↗
PubMed1997

[Effect of heparin on the increase in intracellular calcium caused by inositol 1,4,5-triphosphate in airway epithelial cells].

We studied the effect of heparin on the inositol 1,4,5-triphosphate (IP3)-dependent increase in intracellular calcium (Ca2+) caused by ATP. The Ca2+ concentration ([Ca2+]i) in cultured epithelial cells from cow tracheas was measured by the fura-2 method. ATP (10(-4) M) stimulated IP3 production and caused a biphasic increase in [Ca2+]i a transient response and a subsequent sustained response. Heparin (l 100 U/ml) dose-dependently inhibited the ATP-induced increase in [Ca2+]i but had no effect on IP3 production. Dextran sulfate, a polysaccharide with negative charge density, had a similar inhibitory effect on the ATP-induced increase in [Ca2+]i. These data suggest that heparin inhibits intracellular Ca2+ mobilization by acting at a site "distal to" IP3 production, and that the mechanism of action of heparin may be related to its negative charge.

Adenosine Triphosphate↗
PubMed1997

Recording multifocal electroretinograms with fundus monitoring.

PURPOSE: To record multifocal electroretinograms (ERGs) with simultaneous fundus monitoring. METHODS: An infrared television fundus camera was used to monitor the fundus. A tightly packed array of 19 yellow light-emitting diodes (LEDs) was used as the stimulus source and LEDs were alternated between on and off according to a binary m-sequence at a rate of 75 Hz. The stimulus array subtended approximately 25 degrees of the visual angle. Multifocal ERGs were recorded with a Burian-Allen bipolar contact lens electrode from two normal subjects and a patient with macular dystrophy. RESULTS: When the center of the stimulus was positioned on the fovea, the amplitude of the response was largest at the fovea and decreased toward the peripheral retina; the response pattern corresponded to the spatial distribution of cone cells. When the center of the stimulus was positioned on the optic disc, the response at the optic disc was undetectable. A reliable multifocal ERG was obtained from a patient with macular dystrophy. CONCLUSIONS: This system made it possible to monitor the stimulus on the fundus and to adjust the stimulus to the correct retinal locations with exact focusing. The authors' findings indicate that this method especially can be useful in patients with poor fixation. In addition, the authors' results suggests that the stray light effect in the multifocal stimulus system is minimal if any.

Adult↗
PubMed1997

Altered transcriptional regulation of the insulin-like growth factor 2 gene in human hepatocellular carcinoma.

The insulin-like growth factor 2 (IGF2) gene is regulated in a complex manner, involving developmentally regulated use of four different promoters as well as transcriptional repression of the maternal allele due to genomic imprinting. It has been well documented that liver is an exceptional organ in which overall transcription from the four IGF2 promoters is markedly imbalanced towards preferential paternal expression only in fetal life, this being relaxed during the postnatal period, resulting in biallelic expression thereafter. We previously reported a marked allelic-expression imbalance in the overall transcription of IGF2 in hepatocellular carcinoma (HCC), leading to preferential expression nonrandomly from the paternal allele. The study presented here, using 18 HCC specimens taken directly from patients, showed that this molecular change often reflects promoters switching from the adult P1 promoter to the fetal P2, P3, and P4 promoters. Interestingly, however, we found that restoration of allele-specific expression of the P1 promoter nonrandomly from the paternal allele was also frequent in HCC suggesting retention of an imprint for paternal expression from the P1 promoter of IGF2 in adult normal liver and altered availability of its modifying factor or factors in HCC. Further studies of the molecular mechanisms involved in the fluctuation of promoter usage and genomic imprinting of IGF2 are warranted to gain an insight into the biology of the liver in terms of development and oncogenesis.

Adult↗
PubMed1997

[The effect of age on short-wavelength sensitive cone electroretinograms and long-and middle-wavelength sensitive cone electroretinograms].

We studied the effect of age on short-wavelength sensitive cone electroretinogram (S-cone ERG) and long-and middle-wavelength sensitive cone ERG (LM-cone ERG) using a contact lens electrode with a built-in light-emitting diode. We recorded ERGs in 31 pseudophakic subjects to avoid the effect of yellowing in human crystalline lens. The intensities of our stimuli were on the asymptote of the intensity-response curve. We performed linear regression analysis against age on the S-cone ERG b-wave (S-b), and the LM-cone ERG a-, b- and d-waves (LM-a, LM-b, LM-d). We found significant age-dependent reduction in the amplitude of S-b, LM-a, and LM-d, significant prolongation in the peak time of LM-b and LM-d, and significant increase in the b/a ratio of the LM-cone ERG, but no significant age correlation between the peak time of S-b and LM-a and the amplitude of the b-wave. Our results provide evidence that age-related changes in S- and LM-cone systems begin in the twenties in humans. Furthermore, a significant increase of the b/a ratio suggests that off-bipolar cells are more vulnerable to aging than on-bipolar cells.

Adult↗
PubMed1997

[A case report on prosthetic valve dysfunction of the Carpentier-Edwards pericardial bioprosthesis in the tricuspid position associated with remarkable hypoproteinemia].

A 66-year-old woman underwent a second tricuspid valve replacement because of a malfunction of the Carpentier-Edwards pericardial bioprosthesis (CEP) in the tricuspid position 3.5 years after her first mitral and tricuspid valve replacement. The major symptom was lower leg edema and a serum albumin level ranging between 1.5 g/dl and 2.0 g/dl. The remarkable hypoproteinemia might have resulted from impaired albumin synthesis due to liver dysfunction, hemodilution, protein losing gastroenteropathy, and changes in albumin distribution due to edema. Although the explanted CEP showed neither dehiscence nor calcification of the leaflet, fibrous pannus mainly on the ventricular side restricted the mobility of the corresponding leaflet. Patients receiving a CEP in the tricuspid position should receive careful follow-up.

Aged↗
PubMed1997

Effect of the histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-methylamino ) methyl-2-furyl] methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine on acute gastric mucosal injury in rats and its free-radical scavenging activities.

The protective effect of T-593 ((+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H2-receptor antagonist, was investigated in rats with acute gastric mucosal injury. An ischemic injury followed by reperfusion was produced by applying a small vascular clamp to the celiac artery for 30 min and then removing it for 60 min. T-593 significantly reduced the area of the lesion in the stomach in a dose-dependent manner, and doses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hydroxyl radicals generated by the hydrogen peroxide-ferrous iron sulfate system. T-593 also significantly inhibited the increase of lipid peroxides induced by free-radical initiators in gastric mucosal homogenates. Thus, the protective effect of T-593 against acute gastric mucosal injury induced by ischemia and followed by reperfusion may result, in part, from its antioxidant properties.

Animals↗
PubMed1997

[Role of neutrophil elastase in allergen-induced airway microvascular leakage in sensitized guinea pigs].

To determine the role of neutrophil elastase in allergen-induced airway microvascular leakage, we assessed vascular permeability of guinea pig trachea by measuring the extravasation of Evans blue dye in the circulating blood. Inhalation of ovalbumin (OA) to guinea pigs sensitized with OA caused Evans blue extravasation, indicating an increased microvascular permeability. Pretreatment with ONO-5046 a specific inhibitor of neutrophil elastase, inhibited OA-induced vascular leakage in a dose-dependent manner. Tracheal instillation of human neutrophil elastase likewise increased microvascular permeability, and this effect was almost completely abolished by ONO-5046. Challenge with OA increased the number of neutrophils and neutrophil elastase activity in the bronchoalveolar lavage fluid, and these effects were inhibited by ONO-5046. These results suggest that neutrophil accumulation into the airway and the subsequent release of neutrophil elastase may play a role in the airway microvascular leakage produced by antigen challenge.

Animals↗
PubMed1997

[Vitreous surgery for macular hole followed membrane peeling].

We performed vitreous surgery for macular holes following membrane peeling. The cases were five eyes of five females aged 42 to 67 years at the time of membrane peeling, out of 441 eyes of 414 patients who underwent membrane peeling. One eye had secondary epiretinal membrane combined with ocular sarcoidosis, two eyes had idiopathic epiretinal membrane, and two eyes had idiopathic vitreoretinal traction syndrome. The presumed interval from membrane peeling to macular hole formation was 5 to 90 months (average 14 months). For treatment of the macular holes, membrane peeling and SF6 gas tamponade were performed. In four eyes of the five eyes, the macular hole was closed. In the remaining eye, removal of the retinal pigment epithelium from the base of macular hole and application of fibrin glue were used in addition to SF6 gas tamponade, but the macular hole was not closed. The follow-up term was 10-24 months (average 17.6 months). Geometrical mean visual acuity was 0.34 before membrane peeling, 0.94 at maximum after membrane peeling, 0.19 after macular hole formation, 0.51 at maximum after macular hole surgery, and 0.44 at the final visit.

Adult↗
PubMed1997

[Influence of preanesthetic medication on the effect of a local anesthetic tape].

We investigated the influence of preanesthetic medication on the pain relieving effect of the lidocaine tape during needle insertion for venous cannulation. Ninety patients scheduled for elective surgery were randomly divided into three groups of 30 each; patients without preanesthetic medication (group N), patients who received 0.1 mg.kg-1 of diazepam (group D) and 5 micrograms.kg-1 of clonidine (group C) as a preanesthetic medication. Ninety minutes before the induction of anesthesia, we applied a lidocaine tape to each patient. The grade of pain at the pinprick test and at the venous puncture was evaluated in the operating room. No significant difference of the pain score was seen between the groups. We concluded that the effect of lidocaine tape was not influenced by the preanesthetic medication.

Adjuvants, Anesthesia↗
PubMed1997

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

Antigens, CD↗
PubMed1997

Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin.

In the present study, we developed an antitumor immunoconjugate that appears to be promising as a novel curative antitumor agent against a variety of human solid tumors. We generated a new antihuman endoglin (EDG) monoclonal antibody (mAb) K4-2C10 (or termed SN6f) that cross-reacts with mouse endothelial cells. Such cross-reactive anti-EDG mAbs have not been reported previously. This mAb was used to target tumor-associated vasculature in SCID mice inoculated with human tumors. No anti-EDG mAb or its immunoconjugates have previously been successfully used for targeting vasculature in vivo. In this study, MCF-7 human breast cancer cells were inoculated s.c. into SCID mice. K4-2C10 did not react with the MCF-7 cells but showed a weak reactivity with mouse endothelial cells. The mAb reacted with the proliferating endothelial cells more strongly than with the quiescent endothelial cells. The mAb exhibited much stronger reactivity (>10-fold) with human endothelial cells than with mouse endothelial cells and reacted strongly with vascular endothelium of tumor-associated blood vessels in a variety of human malignant tissues. Conjugates of K4-2C10 with ricin A chain (RA) and deglycosylated ricin A chain (dgRA) showed a weak but specific cytotoxic activity against murine endothelial cells in vitro; the 50% inhibitory dose of the RA and dgRA conjugates was 54 nm and 29 nm, respectively. Remarkable antitumor efficacy was observed when a small amount (a total of 60 microgram corresponding to 24% of the LD50 dose) of the dgRA conjugate was administered i.v. into SCID mice that had been inoculated s.c. with MCF-7. Unconjugated mAb K4-2C10 was not significantly effective in the inhibition of the tumor growth. The immunotoxin (IT) completely inhibited growth of the tumor in all of the treated mice (n = 8). Furthermore, similar antitumor efficacy was observed when the IT was administered i.v. into the tumor-inoculated SCID mice that had been pretreated with unconjugated K4-2C10 to block the potentially available weak binding sites of normal tissues. The strong therapeutic effects of the IT were reproduced in another set of therapeutic experiments. No significant side effects were observed in the mice. The differences in the tumor growth between the control group and the IT-treated groups were statistically significant. The IT showed antiangiogenic activity in the dorsal air sac method. The results indicate that K4-2C10 IT effectively treated the tumor-bearing mice by selectively inhibiting the tumor-associated blood vessels and by disrupting tumor-associated angiogenesis. The strong antitumor efficacy of the K4-2C10 IT is remarkable in view of the fact that K4-2C10 and its IT showed only a weak reactivity with mouse endothelial cells, and a relatively small amount of the IT was administered i.v. to treat s.c. tumors. We anticipate that the K4-2C10 IT will show much stronger antitumor efficacy and antiangiogenic activity in patients with solid tumors and other angiogenesis-associated diseases. The present results demonstrate for the first time that an anti-EDG mAb or its immunoconjugate can effectively target tumor-associated vasculature in vivo.

Animals↗