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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 73 records · Page 4Linked to original sources
PubMed2001

Tandem repetition of baculovirus ie1 promoter results in upregulation of transcription.

In order to improve a virus-independent gene expression system in insect cells, the effect of the repetition of the promoter sequence of a baculovirus immediate early gene, BmNPV ie1, on the gene expression activity was examined. Tandem repetition of ie1 promoter resulted in about a 4-fold increase of the reporter gene expression activity. Primer extension analysis revealed that the repetition increased not only the amount of transcripts (4 to 5-times) but also the number of sites of transcription initiation (at least 3 extra initiation sites). A mutational experiment demonstrated the involvement of independent cis-acting elements in these two different promoter-enhancing effects.

Animals↗
PubMed2001

Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism caused by deficiency in the glycine cleavage system (GCS); this system consists of four individual constituents, P-, T-, H-, and L-proteins. Several mutations have been identified in P- and T-protein genes, but not in the H-protein gene (GCSH), despite the presence of case reports of H-protein deficiency. To facilitate the mutational and functional analyses of GCSH, we isolated and characterized a human p1-derived artificial chromosome (PAC) clone encoding GCSH. GCSH spanned 13.5kb and consisted of five exons. Using the PAC clone as a probe, we mapped GCSH to chromosome 16q24 by fluorescence in situ hybridization. The transcription initiation site was determined by the oligonucleotide-cap method, and potential binding sites for several transcriptional factors were found in the 5' upstream region. Direct sequencing analysis revealed five single-nucleotide polymorphisms. The expression profiles of P-, T-, and H-protein mRNAs were studied by dot-blot analysis, using total RNA from various human tissues. GCSH was expressed in all 29 tissues examined, while T-protein mRNA was detected in 27 of the 29 tissues. In contrast, the P-protein gene was expressed in a limited number of tissues, such as liver, kidney, brain, pituitary gland, and thyroid gland, suggesting distinct transcriptional regulation of each GCS constituent.

Alleles↗
PubMed2001

Effect of F-1394, an acyl-CoA:cholesterol acyltransferase inhibitor, on atherosclerosis induced by high cholesterol diet in rabbits.

Cholesterol-fed rabbits were used to study the anti-atherosclerotic effect of (1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane-1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor. To test its effect on the development of atherosclerosis, rabbits were fed a high-cholesterol diet (HCD) for 6 weeks, followed by regular chow (RC) for 12 weeks plus 0 or 100 mg/kg per day F-1394. Serum total cholesterol (TC) rose to approximately 2000 mg/dl on HCD and then declined gradually after the change in diet in both groups. F-1394 significantly reduced the extent of the atherosclerotic lesions and the total and esterified cholesterol contents of the aorta (by 57,38, and 59%, respectively), without affecting the serum TC level. To clarify whether F-1394 accelerates the regression of preexisting atherosclerosis, rabbits were fed HCD for the first 6 weeks and then RC for the next 6 weeks. Then, the rabbits were given 0 or 100 x 2 mg/kg per day F-1394 for another 12 weeks while on RC. F-1394 significantly reduced the extent of the atherosclerotic lesions and the total and esterified cholesterol content in the aorta (by 31, 31, and 43%, respectively), without affecting the serum TC level. These results demonstrate that F-1394 both prevents the formation of atherosclerosis and accelerates its regression without affecting the serum TC level, indicating that F-1394 acts directly on the arterial wall.

Animals↗
PubMed2001

Suppression of fibrous adhesion by proteoglycan decorin.

Small proteoglycan decorin is known to suppress the bioactivity of TGF-beta through a competitive binding with the cell surface receptors for the cytokine. Based on this knowledge, we hypothesized that decorin could reduce the formation of fibrous adhesion, because our previous study showed the neutralizing antibody to TGF-beta1 has that effect. An intra-articular adhesion model in the rabbit knee joint was employed in this study, and decorin was administered into the joint cavity continuously during the 4 weeks of the experiment. The results of the dose-response study demonstrated that decorin suppresses formation of fibrous adhesion in a dose-dependent manner. When the administration of decorin was limited to shorter periods, this effect was considerably impaired and the necessity of long-term administration was demonstrated. On the other hand, when administered together with TGF-beta1, decorin still suppressed adhesion but to a lesser extent, and it was suggested that this proteoglycan could have other significant mechanism(s) to suppress adhesion besides the neutralization of TGF-beta. Thus, the present study showed that decorin could inhibit adhesion formation by both TGF-beta dependent and independent mechanisms. Considering that decorin exists ubiquitously in the body, its administration might be a promising approach to suppress adhesion.

Animals↗
PubMed2001

Doxazosin, an alpha1-adrenergic antihypertensive agent, decreases serum oxidized LDL.

Oxidized low-density lipoprotein (ox-LDL) is well known to play an important role in atherogenesis through the recruitment of monocytes into vessel walls and the deposition of cholesterol ester in the macrophages, which leads to the formation of lipid-rich plaque. It was assumed that only trace amounts of ox-LDL were present in plasma because the half-life of ox-LDL was only a few minutes. Recently, through the use of a monoclonal antibody against ox-LDL, a quantitative method to measure serum ox-LDL concentration has been developed. Metabolites of doxazosin, an alpha1-adrenergic antihypertensive agent, have been reported to inhibit oxidation of LDL in vitro. In this study, we investigated the in vivo effect of doxazosin on LDL oxidation using this new method to measure serum ox-LDL concentration. After the administration of doxazosin for 1 to 2 months, serum concentration of ox-LDL decreased significantly (P < .05). Although the reduction of ox-LDL concentration does not strictly indicate doxazosin's antiatherosclerotic effect, it may constitute one of doxazosin's additional weapons beside lowering blood pressure and serum lipid values in the prevention of atherosclerosis.

Adrenergic alpha-Antagonists↗
PubMed2001

Direct effect of an acyl-CoA:cholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice.

The acyl-CoA:cholesterol acyltransferase (ACAT) enzyme is thought to be responsible for foam cell formation and the subsequent progression of atherosclerosis. The apolipoprotein E and low density lipoprotein receptor double knockout (apoE/LDLr-DKO) mouse is an animal model that develops severe hyperlipidaemia and atherosclerosis. Here we have examined the effect of oral administration of an ACAT inhibitor, F-1394, on atherosclerosis in apoE/LDLr-DKO mice fed a regular chow diet. In en face analysis, a dose of 10, 30, or 100 mg kg(-1) day(-1) F-1394 for 10 weeks reduced the extent of lesions visible in the aorta by 24, 28 and 38%, respectively, as detected by staining with oil red O, without affecting serum cholesterol level in these mice. At the highest dose 100 mg kg(-1) day(-1) of F-1394, the reduction was statistically significant. For quantitative analysis of the cellular and non-cellular components comprising the lesions at the aortic sinus, the effects of an oral dose of 100 mg kg(-1) day(-1) F-1394 for 15 weeks were studied. There was a significant reduction (31.9%) in the oil-red O-stained area in cross-sections of the aortic sinus. In addition, the neointimal area, as well as levels of ACAT-1 protein tended to be decreased (15.2 and 25.8%, respectively, not significant). However, the areas containing macrophages, smooth muscle cells, and collagen were not affected by F-1394. In vitro, F-1394 attenuated foam cell formation in mouse peritoneal macrophages. These results indicate that ACAT may be primarily responsible for lipid accumulation in atherosclerotic lesions, and that its inhibition diminishes the lipid deposition via a direct effect on macrophages in the arterial wall.

Animals↗
PubMed2001

Screening of ischemic heart disease with cavernous artery blood flow in erectile dysfunctional patients.

Erection is a hemodynamic event and accordingly, erectile dysfunction (ED) is closely related with ischemic heart disease. We should confirm that the cardiac condition of the ED patient is safe enough to perform sexual intercourse prior to beginning treatment for ED. Asymptomatic ischemic heart disease cannot be diagnosed only in an interview, but it's difficult to perform cardiac exercise tests on all patients complaining of ED. Therefore, screening methods to evaluate patients who should undergo exercise tests are needed. Sixty patients with erectile dysfunction participated in this study. Physical examinations, interviews, and color Doppler examinations were conducted. Chest X-rays and electrocardiograms of all patients in the resting position were obtained, as were electrocardiograms following exercise. Echocardiograms, treadmill test results, thallium exercise scintigrams, and coronary angiograms were obtained as required for diagnosis. Two patients were excluded because they had obvious arteriogenic ED due to perineal injury. Fifty-eight patients underwent Doppler evaluations of their cavernous arteries and heart exercise tests. Fourteen patients (24.1%) were diagnosed with ischemic heart disease. Although six of them had already been diagnosed with ischemic heart disease, eight were newly diagnosed by the exercise tests. Cardiovascular risk factors such as advanced age, hyperlipidemia, diabetes mellitus, hypertension, smoking, and obesity were not sufficient predictive factors. The mean peak systolic velocity of the patients without ischemic heart disease was 34.6 cm/s vs 22.0 cm/s in those with ischemic heart disease. Only 3.7% of patients whose peak systolic velocity in the cavernous artery was equal to or exceeded 35 cm/s had ischemic heart disease. On the other hand, 41.9% of patients with peak systolic velocity of less than 35 cm/s had ischemic heart disease. The sensitivity of peak systolic velocity against ischemic heart disease was 92.9%, and specificity was 59.1%. In ED patients, incidences of complications involving symptomatic or asymptomatic ischemic heart disease were found to be high. The peak systolic velocity in the cavernous artery is thought to be a useful predictive factor of ischemic heart disease in ED patients. When a patient reveals a peak systolic velocity of less than 35 cm/s, he should undergo heart exercise tests prior to treatment of ED.

Adult↗
PubMed2001

Spring balance evaluation of the ischiocavernosus muscle.

We studied the voluntary contractile activity of the ischiocavernosus muscle (ICM) in 21 sexually potent and 97 erectile dysfunction (ED) subjects using a spring balance. A strap was placed around the coronal grove of the glans penis and tensioned with the spring balance. Subjects were asked and encouraged to contract the ICM against the spring balance. We evaluated the length of stroke, duration of contraction, and maximum contractile force. The length of stroke, duration of contraction, and maximum contractile force showed statistically significant differences between potent and ED subjects. Diagnosed psychogenic ED and arteriogenic ED showed higher contractile activity than cavernous ED and neurogenic ED. Our results corresponded to those of previous studies that have urged consideration of the role of the ICM during the process of erection in animal experiments and in human electrophysiological studies. The spring balance evaluation is a useful, inexpensive method for evaluating the ICM.

Adolescent↗
PubMed2001

Integration of microfabricated needle-type glucose sensor devices with a novel thin-film Ag/AgCl electrode and plasma-polymerized thin film: mass production techniques.

We developed an integrated array of needle-type biosensors employing a novel process of fabrication, comprising conventional semiconductor fabrication and micromachining technology. Amperometric sensing electrodes with plasma-polymerized films and a thin-film Ag/AgCl reference electrode were directly integrated on a glass substrate with thin-film process, e.g., sputtering. An enzyme was immobilized on the electrode via the plasma-polymerized film, which was deposited directly on the substrate using a dry process. The novel thin-film Ag/AgCl reference electrode showed stable potentials in concentrated chloride solutions for a long period. The plasma-polymerized film is considered to play an important role as an interfacial design between the sensing electrode and the immobilized enzyme considering that the film is extremely thin, adheres well to the substrate (electrode) and has a highly cross-linked network structure and functional groups, such as amino groups. The results showed increments of the sensor signal, probably because the plasma-polymerized film allowed a large amount of enzyme to be immobilized. The greatest advantage is that the process can permit the mass production of high-quality biosensors at a low cost.

Biosensing Techniques↗
PubMed2001

A case of successful fetal therapy for congenital chylothorax by intrapleural injection of OK-432.

A 38-year-old multiparous woman was referred at 19 weeks' gestation because of hydrops fetalis. Ultrasonic examination revealed severe pleural effusion, ascites and skin edema. Detailed examination of the amniotic fluid, fetal blood and intrathoracic fluid led to a diagnosis of congenital fetal chylothorax. Repeated thoracocenteses were not effective in improving the hydrops fetalis. We introduced fetal treatment for the pleural effusion by an intrapleural injection of OK-432 at 23, 24 and 25 weeks' gestation. The pleural effusion was reduced by adhesion of the intrathoracic space and resulted in the delivery of a neonate who was healthy except for right renal dysfunction. Pulmonary hypoplasia was successfully prevented by OK-432.

Adult↗
PubMed2001

Comparison of sevoflurane with isoflurane for rapid mask induction in midazolam and butorphanol-sedated dogs.

Rapid mask induction can be a useful induction technique for veterinary patients, although it is often accompanied by exaggerated excitement responses in unpremedicated animals (Mutoh et al.: Jpn. J. Vet. Anesth. Surg. 26, 109-116; J. Vet. Med. Sci. 57, 1007-1013; J. Vet. Med. Sci. 57, 1121-1124; 1995). The aim of this study was to compare sevoflurane with isoflurane for rapid mask induction in six dogs sedated by a combination of midazolam (0.1 mg/kg) and butorphanol (0.2 mg/kg). Induction with sevoflurane (5%, 2.4 minimum alveolar concentration [MAC]) in O2 resulted in shorter time to loss of the palpebral reflex, negative tail clamp response, and successful intubation than with isoflurane (3%, 2.4 MAC) in O2. There were no changes in heart rate or mean arterial blood pressure during induction with sevoflurane, whereas an increase in heart rate was observed in dogs induced with isoflurane. A decrease in respiratory rate compared with the pre-induction rate was observed during induction, and associated mild respiratory acidosis, characterized by an increase in arterial PCO2, was measured at the end of the induction period in both induction groups. None of the animals had episodes of induction-related complications. These results suggest that both sevoflurane and isoflurane produce a smooth onset of induction in midazolam and butorphanol-sedated dogs. Sevoflurane is a more suitable for rapid mask induction than isoflurane since it provides faster induction associated with a lower blood/gas partition coefficient.

Anesthesia, Inhalation↗
PubMed2001

Medium-chain fatty acids stimulate interleukin-8 production in Caco-2 cells with different mechanisms from long-chain fatty acids.

BACKGROUND AND AIM: It has been suggested that dietary fat exacerbates intestinal inflammation. We investigated the effect of fatty acids on interleukin (IL)-8 production in a human intestinal epithelial cell line (Caco-2). METHODS: The cells were cultured as monolayers on microporous membranes in culture inserts. Oleic acid (OA), capric acid (CA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were applied to the apical compartment of Caco-2 cell monolayers. The concentration of IL-8 in the basolateral medium was measured by using enzyme-linked immunosorbent assay, and the expression of IL-8 mRNA was measured by using competitive reverse transcription--polymerase chain reaction. Protein kinase C inhibitors (GF109203X and calphostin C) and H-7 (a protein kinase inhibitor) were used to study the mechanisms by which IL-8 production is stimulated. RESULTS: Both OA and CA enhanced IL-8 production (approximately fivefold), whereas DHA and EPA did not. Both OA and CA also enhanced IL-1-induced IL-8 production. The onset of OA-induced IL-8 production was delayed compared with that of CA-induced IL-8 production. Both OA and CA enhanced IL-8 mRNA expression (approximately fivefold) after 6 and 3 h, respectively. The protein kinase inhibitor (H-7) reduced both OA- and CA-induced IL-8 production by 88.0 and 85.9%, respectively. The protein kinase C inhibitors (GF109203X and calphostin C) reduced OA-induced IL-8 production by 29.3 and 54.5%, respectively, but showed no effect on CA-induced IL-8 production. CONCLUSIONS: These findings suggest that not only OA but also CA stimulates IL-8 production in intestinal epithelial cells, and the mechanisms of action differ between OA and CA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

P300 abnormalities in patients with severe sleep apnea syndrome.

We investigated the mechanism of abnormal P300 findings in the patients with severe sleep apnea syndrome (SAS). Compared with controls, SAS patients showed significantly longer latency of P300. Not the mean sleep latency in multiple sleep latency test but the percentage of total periods in which percentage desaturation time fell below 90% to total sleep time correlated with P300 latency in the patients. During nasal CPAP treatment, P300 latency was significantly shortened in the patients under 45 years, while the elderly patients did not show statistical change. We speculated that P300 latencies might be prolonged due to nocturnal hypoxia with SAS and the abnormality might be irreversible, especially in elderly patients.

Adult↗
PubMed2001

Hypothalamically induced emotional behavior and immunological changes in the cat.

Numerous animal studies on the correlation between stress and immunity have been performed but few such studies have been made concerning the relationship between various kinds of stress-related emotional behavior and immunological changes. Electrical stimulation of the hypothalamus in cats elicits various emotional behaviors such as restlessness, defensive attack, defensive retreat and quiet biting attack. We examined changes in the lymphocyte proliferative responses and plasma cortisol level which accompanied such emotional behavior. A significant increase in plasma cortisol was observed in the restlessness, defensive attack and defensive retreat groups, but not in the quiet biting attack or non-response (control) groups. A significant increase in the lymphocyte proliferative responses to phytohemagglutinin (PHA) was observed in the restlessness and defensive attack groups but not in the defensive retreat, quiet biting attack or non-response groups. These results suggest that various kinds of emotional behavior appear to be differentially correlated with the lymphocyte proliferative responses, while also being differentially correlated with the plasma cortisol concentration. Because the changes in lymphocyte responses and plasma cortisol did not always completely correlate with one another, the changes in the lymphocyte responses are not considered to be influenced by plasma cortisol alone.

Animals↗
PubMed2001

Effect of radical retropubic prostatectomy on erectile function, evaluated before and after surgery using colour Doppler ultrasonography and nocturnal penile tumescence monitoring.

OBJECTIVE: To assess the effect of radical retropubic prostatectomy on erectile function, by evaluating objectively patients' erectile function before and after surgery. PATIENTS AND METHODS: The study comprised 126 patients with clinically localized prostate cancer who were scheduled to undergo radical retropubic prostatectomy. After giving informed consent for the study, 123 patients underwent intracavernosal injection tests, colour Doppler ultrasonography and nocturnal penile tumescence monitoring before and after surgery. RESULTS: From the intracavernosal injection tests and nocturnal penile tumescence monitoring, 21 patients (17%) were evaluated as having normal erectile function before surgery. After radical retropubic prostatectomy, nine (43%) of these 21 potent men had preserved erectile function. In eight patients whose neurovascular bundles were preserved, five were potent after surgery. The cause of erectile function after surgery was a neurogenic disorder in seven and a related vascular disorder in five. CONCLUSION: From objective tests of erectile function on patients scheduled to undergo radical prostatectomy, 17% had normal erectile function. However, even after nerve-sparing radical retropubic prostatectomy, the proportion retaining potency was unsatisfactory. Although a neurological disorder was the main cause of erectile dysfunction after surgery, vascular disorders were also important.

Aged↗
PubMed2001

Feasibility of multi-slice computed tomography in the diagnosis of arteriogenic erectile dysfunction.

OBJECTIVE: To compare computed tomography (CT) angiography (CTA) obtained by multi-slice CT (a new minimally invasive method) with the current standard of arterial imaging, digital subtraction angiography (DSA), in diagnosing arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS: Twenty-one patients with suspected arteriogenic ED underwent DSA and CTA after providing informed consent. Prostaglandin E1 was injected into the penile cavernosal body and then non-ionic contrast medium was rapidly infused into the antecubital vein. The DSA and CTA images were diagnosed as showing a normal or abnormal status by three reviewers independently. CTA was undertaken on an outpatient basis but DSA required hospitalization. RESULTS: In the 42 internal pudendal arteries, DSA showed 28 normal and 14 impaired arteries; CTA showed 21 normal arteries and 21 occlusions. The CTA image correlated closely with the diagnosis of stenosis or occlusion in internal pudendal arteries, with a sensitivity of 93%, a specificity of 71% and an accuracy of 79%. In the cavernosal arteries, DSA depicted 14 normal and 28 impaired arteries; CTA showed seven normal arteries and 35 occlusions. The CTA image agreed closely with the diagnosis of stenosis or occlusion in cavernosal arteries, with a sensitivity of 96%, a specificity of 43% and an accuracy of 79%. Of the 42 inferior epigastric arteries, DSA could not depict 11 arteries but CTA showed all 42 inferior epigastric arteries. CONCLUSIONS: CTA images correlated with DSA images; at present DSA is better than CTA in visualizing stenosis in fine arteries. However, CTA is less invasive and relatively inexpensive, and in future will probably provide even greater improvements in graphic quality. CTA would be an adequate replacement for DSA in evaluating internal pudendal arterial stenosis.

Adult↗
PubMed2001

The index of motor current amplitude has feasibility in control for continuous flow pumps and evaluation of left ventricular function.

The index of motor current amplitude (ICA) has feasibility in continuous-flow ventricular assist device control. It can demonstrate the safe range of pump speed, which exists between the starting point of total assistance (t-point) and the starting point of sucking (s-point). The objective of this study was to investigate how the ICA characteristic curve changes with each condition of contractility, preload, and afterload changes. We changed preload, afterload, and contractility of closed-mock circulation and plotted the change of the ICA value against pump speed. Then the shift of ICA characteristic curve against the change of each condition was considered. When preload increased, ICA characteristic curves showed the expansion of a safe range. When afterload increased, ICA characteristic curves were shifted to the high rotation side, slightly narrowing a safe range. When contractility increased, ICA characteristic curves showed the shift of a convex above to narrowing of a safe range. As these shift patterns were observed even when the driving conditions of a circuit changed, reproducibility was checked. Understanding the feature of a shift pattern of ICA characteristic curves correctly, a possibility that change of the heart function could be predicted by change of ICA value and a possibility for a flexible control method based on ICA, according to hemodynamic state, were suggested.

Blood Flow Velocity↗