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Biomedical subjects

Y Kajimoto

Publications and source records attributed to Y Kajimoto.

At least 55 records · Page 3Linked to original sources
PubMed1998

Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report.

BACKGROUND: Fluorescein has been used in the field of neurosurgery; however, fluorescein enhancement or contrast proved to be inadequate because of a lack of appropriate light sources or filters. A new operative microscope system, in which the microscope itself is equipped with excitation and barrier filters, and the application of this system to surgery for malignant glioma are reported. METHODS: BP 450-490, a glass interference filter used as the excitation filter for the light source optical system, and a Kodak Wratten No. 12 filter used as the barrier filter for the microscope optical system, were incorporated in the operative microscope. A switching apparatus was devised so that filters could be inserted instantly when fluorescence was to be observed. Ten cases in which the location of malignant glioma was enhanced by computed tomography (CT) or magnetic resonance imaging (MRI) were selected for this study. After incision of the dura mater, 8 mg/Kg body weight of fluorescein Na was injected intravenously. Tumor removal was begun some 20 min after the injection with the aid of this newly developed fluorescein operative microscope system. RESULTS: Fluorescence enhancement and contrast were remarkable when this system was used. It enabled surgical maneuvering while viewing the fluorescent image of objects. The boundaries between the tumor areas enhanced by CT or MRI and the surrounding brain could be clearly distinguished in the fluorescent image; the tumor was totally removed, except for deep lesions, without any neurological deterioration. When the tumor was relatively hard, the area surrounding the tumor was aspirated with a cavitron ultrasonic surgical aspirator; as a result, the tumor could be removed en bloc; otherwise, the fluorescent tumor was removed piece by piece. CONCLUSIONS: This system provides adequate fluorescent enhancement and contrast and is useful for observing intravenously injected fluorescein during an operation. Though long-term follow-up of such cases is needed, the conditions of our patients immediately after surgery for malignant glioma were satisfactory. These results suggest that our fluorescein operative microscope system is highly effective in surgery for malignant glioma.

Adult↗
PubMed1998

Effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy.

OBJECTIVE: Although some studies have suggested a direct action of troglitazone on vascular cells, its effects on diabetic vascular diseases have not been reported. We therefore investigated the effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 30 patients with type 2 diabetes associated with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] [milligrams per gram creatinine] ranging from 30 to 300 mg/g creatinine) were studied. They were randomly divided into two groups: patients treated with metformin (500 mg/day, n = 13) or with troglitazone (400 mg/day, n = 17) for 12 weeks. ACR, lipid profile, blood pressure, glycated hemoglobin, and plasma glucose during meal-load tests were measured every 4 weeks. RESULTS: Anthropometric indices (BMI and percent fat), lipid profile, and blood pressure did not change with either treatment. Fasting and postmeal glucose levels decreased similarly in the two groups. Decrements in glycated hemoglobin were greater in the metformin group at 4 and 8 weeks after the initiation of treatment (P < 0.05). Troglitazone reduced ACR (median [25-75th percentiles]) from 70 (49-195) to 40 (31-90) mg/g creatinine at 4 weeks (P = 0.021) and maintained these reduced levels throughout the treatment period (8 weeks: 35 [26-68], P = 0.007; 12 weeks: 43 [26-103], P = 0.047). Metformin did not change ACR throughout the 12 weeks. CONCLUSIONS: Troglitazone ameliorated microalbuminuria in diabetic nephropathy. Furthermore, our findings suggest that troglitazone has some effects on vascular cells other than lowering plasma glucose levels. Troglitazone might be useful for diabetic angiopathy, including nephropathy and coronary artery disease.

Aged↗
PubMed1997

Expression of heparin-binding epidermal growth factor-like growth factor during pancreas development. A potential role of PDX-1 in transcriptional activation.

The development of the pancreas appears to be regulated by various growth factors. We report here the expression of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in the developing pancreas. Immunostaining of fetal and neonatal rat pancreata, in which endocrine cells are visible as cell clusters often associated with primitive ducts or ductular cells, revealed that most of the cluster-forming cells and primitive ducts or ductular cells express HB-EGF protein. In contrast, the exocrine pancreas lacked HB-EGF expression. Based on findings that the expression pattern was similar to that of the homeodomain-containing transcription factor PDX-1 (IDX-1/STF-1/IPF1) and that the regulatory region of the HB-EGF gene contained sequences similar to the PDX-1-binding A element, we examined whether PDX-1 could be a potential activator of HB-EGF gene expression. The results of reporter gene analyses suggested that the HB-EGF gene promoter is PDX-1-responsive and that the activity of the promoter in pancreatic beta cell-derived betaTC1 cells depends on the PDX-1 binding site-like sequences. Gel-mobility shift analyses using an anti-PDX-1 antibody indicated that PDX-1 is a specific and dominant binding factor for an A element-like sequence in the HB-EGF gene. These observations suggest the possible involvement of HB-EGF in pancreas development. While PDX-1 is essential for pancreas development, HB-EGF may function as a mediator of PDX-1 and thus be involved in the development of the endocrine pancreas.

Animals↗
PubMed1997

Suppression of transcription factor PDX-1/IPF1/STF-1/IDX-1 causes no decrease in insulin mRNA in MIN6 cells.

The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.

Binding Sites↗
PubMed1997

Sensitive, selective gas chromatographic-mass spectrometric analysis with trifluoroacetyl derivatives and a stable isotope for studying tissue sorbitol-producing activity.

One of the major mechanisms involved in diabetic microangiopathy is considered to be an altered polyol pathway. However, clarifying the pathophysiology is difficult due to the lack of a sensitive method for measuring the reduction of glucose to sorbitol in tissue. Here we report a sensitive and selective method for polyol measurement using trifluoroacetyl (TFA) derivatives of polyols and stable isotope-labeled D-sorbitol (U-[13C]sorbitol, 13C6H14O6, 98.7%) as an internal standard. Gas chromatography-mass spectrometry (GC-MS) using an SE-30 capillary column gave elution of TFA derivatives of sugars, polyols and U-[13C]sorbitol within 8 min, with clear separation of sorbitol. In the calibration study, the coefficients of correlation between the amount of sorbitol added and that determined in standard solutions containing 0.1-8.0 nmol sorbitol, erythrocyte mixture and liver cytosol mixture were r = 0.999, r = 0.997 and r = 0.997, respectively. The precision of the GC-MS measurement of standard solution was C.V. = 4.3%. Because glucose is used as a substrate, the method can clarify the polyol pathway under physiological conditions. With this method, Km and Vmax values of the reductase in erythrocytes were 115 +/- 19 mmol/l and 4.42 +/- nmol/min/g of hemoglobin. In human liver, on the other hand, they were 755 +/- 132 mmol/l and 0.773 +/- 0.090 nmol/min/mg of protein, respectively. This difference of Km values suggested that aldehyde reductase rather than aldose reductase is mainly responsible for reducing glucose to sorbitol in the liver. In conclusion, this newly developed method offers a highly sensitive and selective procedure for measuring low concentrations of sorbitol in various tissues and cells and should enable clarification of the kinetics of glucose reduction to sorbitol, which in turn can be used to evaluate the role of an altered polyol pathway in the pathophysiology of diabetic microangiopathy.

Adolescent↗
PubMed1997

Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells.

Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from pancreatic beta cells, accompanied by a decrease in the insulin content of the cells. As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to pancreatic beta cells, we induced glycation in HIT-T15 cells using a sugar with strong deoxidizing activity, D-ribose, and examined the effects on insulin gene transcription. The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter; approximately 50 and 80% of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose, respectively. In agreement with this, decrease in the insulin mRNA and insulin content was observed in the glycation-induced cells. Also, gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor, PDX-1/IPF1/STF-1. These effects of D-ribose seemed almost irreversible but could be prevented by addition of 1 mM aminoguanidine or 10 mM N-acetylcysteine, thus suggesting that glycation and reactive oxygen species, generated through the glycation reaction, serve as mediators of the phenomena. These observations suggest that protein glycation in pancreatic beta cells, which occurs in vivo under chronic hyperglycemia, suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity.

Acetylcysteine↗
PubMed1997

The Arg192 isoform of paraoxonase with low sarin-hydrolyzing activity is dominant in the Japanese.

The high-density-lipoprotein-associated enzyme paraoxonase, which has a role in the detoxification of organophosphorus compounds, is known to be polymorphic in humans. The Arg192 isoform of paraoxonase hydrolyzes paraoxon more rapidly than the Gln192 isoform. However, with respect to the hydrolysis of toxic nerve agents, such as diazoxon, soman, and sarin, the Arg192 isoform displays a lower activity than the other isoform. To evaluate the possibility that the genetic polymorphism was involved in the aggravated extent of human injury in the sarin gas poisoning incident in the Tokyo subway in March 1995, we investigated the prevalance of this polymorphism in the Japanese population. We found that the Arg192 allele is more common in the Japanese (allele frequency: 0.66) than in people of other races (ranging 0.24-0.31). In the Japanese, 135 out of the 326 subjects (41.4%) investigated were homozygous for the Arg192 allele, which shows a very low hydrolysis activity for sarin. Thus, there seems to be a racial difference in vulnerability to toxic nerve agents, such as sarin. The dominance of the Arg192 allele in the Japanese population probably worsened the tragedy of March 1995 in the Tokyo subway.

Alleles↗
PubMed1997

Comparison of epidural morphine and oxycodone for pain after abdominal surgery.

STUDY OBJECTIVE: To compare the efficacy and side effects of epidural morphine and oxycodone for pain following major abdominal surgery. DESIGN: Randomized, double-blind study. SETTING: 4th Department of Surgery, Helsinki University Central Hospital. PATIENTS: 44 adult ASA physical status I, II, and III patients scheduled for elective major abdominal surgery. INTERVENTIONS: Thirty-three patients were allocated randomly to one of two epidural groups and 11 patients received oxycodone intravenously (IV). The two epidural groups received either morphine (bolus 0.015 mg/kg followed by an infusion 0.003 mg/kg/hr) or oxycodone (bolus 0.15 mg/kg followed by an infusion 0.03 mg/kg/hr) before induction of standardized anesthesia and for 24 hours thereafter. A third group of patients was given the same dose of IV oxycodone as in the epidural group, serving as an open control group for epidural oxycodone. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn for plasma opioid concentrations. Postoperatively, pain (at rest and during coughing), nausea, pruritus, sedation, respiratory rate, and hemodynamics were recorded until the end of the infusions. The epidural dose ratio between morphine and oxycodone was 1:8.4 to 9.8 to provide similar analgesia. Side effects occurred similarly in the three groups. Mild respiratory depression was seen in all groups, especially in the IV oxycodone group. In all groups, hemodynamic variables remained within normal limits. CONCLUSIONS: In the dosages reported, oxycodone can be used epidurally for acute post-operative pain. The analgesic effect was as good as that of epidural morphine.

Abdomen↗
PubMed1997

Comparison of intrathecally administered urokinase, tissue-type plasminogen activator, and combination of urokinase and lysine-plasminogen for clot lysis after experimental subarachnoid hemorrhage in dogs.

OBJECTIVE: The purpose of this study was to compare the fibrinolytic effect of urokinase (UK) with that of tissue plasminogen activator (tPA) on subarachnoid clots and to investigate the effect of lysine-plasminogen (Lys-plg) on fibrinolytic therapy. METHODS: We measured subarachnoid clot lysis rate chronologically for 24 hours during continuous intrathecal irrigation with tPA or UK alone in a canine subarachnoid hemorrhage model. Also, we measured the clot lysis rate for 24 hours during continuous irrigation with UK and Lys-plg or with UK after preadministration of Lys-plg in the same model. RESULTS: The rate of clot lysis caused by UK and tPA dose-dependently increased up to 3,000 IU/ml and 125,000 IU/ml, respectively. With the same molar concentrations, the lytic effect of tPA was significantly higher than that of UK. The slope of the dose-response curve, however, was almost the same with both agents, and the slope of the dose-response curve of UK and tPA for a 24-hour irrigation was 25 and 23% per log 10 concentration, respectively. On the other hand, clot lysis with the combined use of UK and Lys-plg was higher than that with the single use of UK. Particularly, the preadministration of Lys-plg markedly enhanced clot lysis by UK at the early stage of irrigation. CONCLUSION: Subarachnoid clot lysis can be accelerated by administration of Lys-plg before UK administration and by use of high concentrations of UK or tPA.

Animals↗
PubMed1997

A new ventriculoperitoneal shunt with a telemetric intracranial pressure sensor: clinical experience in 94 patients with hydrocephalus.

OBJECTIVE: We have developed a telemetric intracranial pressure sensor (OSAKA telesensor; Nagano Keiki Seisakusyo Co. Ltd., Tokyo, Japan) and investigated the clinical usefulness of new ventriculoperitoneal shunting with an OSAKA telesensor, an on-off valve, and a programmable valve. METHODS: The OSAKA telesensor was applied in 94 patients at Osaka Medical College between March 1986 and December 1995. Postoperative management, postoperative course, postural change of intracranial pressure (ICP), and zero drift of the OSAKA telesensor were investigated. RESULTS: ICP was measured easily in all patients with no inconvenience. The setting of the programmable valve was adjusted postoperatively 38 times in 25 patients. Postoperative ICP in the upright position was -14.9 +/- 4.5 mm Hg, and the difference in ICP between the supine and the upright position was about 20 mm Hg. The slope of the decrease in ICP with continuous postural changes from the supine to the upright position was steep until about 30 to 45 degrees but became incrementally less or even rose slightly about this angle. The initial slope was steeper when the shunt was open than when the shunt was closed; it was also steeper postoperatively than preoperatively. This initial slope, therefore, may indicate the intracranial compliance. Seven cases of shunt malfunction were diagnosed correctly by ICP measurements. Zero drift of the OSAKA telesensor was easily corrected by comparing the ICP reading from the telesensor with the puncture pressure in the on-off valve. CONCLUSION: The OSAKA telesensor is very useful in the postoperative care and pathophysiological evaluation of patients with hydrocephalus.

Equipment Design↗
PubMed1997

Demonstration of two different processes of beta-cell regeneration in a new diabetic mouse model induced by selective perfusion of alloxan.

To clarify the regeneration process of pancreatic beta-cells, we established a new mouse model of diabetes induced by selective perfusion of alloxan after clamping the superior mesenteric artery. In this model, diabetes could be induced by the destruction of beta-cells in alloxan-perfused segments, while beta-cells in nonperfused segments were spared. Intraperitoneal glucose tolerance tests showed glucose intolerance, which gradually ameliorated and was completely normalized in 1 year with a concomitant increase of insulin content in the pancreas. Histological examination showed neo-islet formation in the alloxan-perfused segment and the proliferation of spared beta-cells in the nonperfused segment. In the alloxan-perfused segment, despite a marked reduction of islets in size and number at an early stage, both the number of islets, including islet-like cell clusters (ICCs), and the relative islet area significantly increased at a later stage. Increased single beta-cells and ICCs were located in close contact with duct cell lining, suggesting that they differentiated from duct cells and that such extra-islet precursor cells may be important for beta-cell regeneration in beta-cell-depleted segment. In addition to beta-cells, some nonhormone cells in ICCs were positive for nuclear insulin promoter factor 1, which indicated that most, if not all, nonhormone cells positive for this factor were beta-cell precursors. In the nonperfused segment, the islet area increased significantly, and the highest 5-bromo-2-deoxyuridine-labeling index in beta-cells was observed at day 5, while the number of islets did not increase significantly. This indicated that the regeneration of islet endocrine cells occurs mostly through the proliferation of preexisting intra-islet beta-cells in the nonperfused segment. In conclusion, the regeneration process of beta-cells varied by circumstance. Our mouse model is useful for studying the mechanism of regeneration, since differentiation and proliferation could be analyzed separately in one pancreas.

Alloxan↗
PubMed1996

Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription.

The AT-rich cis-motif A elements of the insulin gene promoter contribute to directing the gene's expression to pancreatic beta-cells, bound by a homeodomain-containing transcription factor, PDX-1/IPF1/STF-1/IDX-1. The islet amyloid polypeptide (IAPP; amylin) gene, which is also expressed in limited tissues such as pancreatic beta- and delta-cells, contained similar AT-rich sequences in its regulatory sequences. To understand the molecular basis of IAPP gene regulation, we evaluated the possible physiological significance of the motif in human IAPP gene regulation. All of the three typical A element-like sequences that matched the CT-box consensus (AT-1, -207/-202; AT-2, -154/-142; and AT-3, -88/-83) were shown to bind specifically to a nuclear factor in the beta-cell-derived MIN6 cells, which was subsequently identified immunologically as the insulin gene transcription factor PDX-1. When the promoter activity was examined in MIN6 cells, the disruption of AT-1 or AT-3 but not of AT-2 caused a marked reduction in the IAPP gene promoter. Thus, despite the observation that all the three A element-like regions could bind to PDX-1, the AT-2 site may not be involved in mediating the PDX-1 action in vivo. These observations suggest the involvement of PDX-1 in human IAPP gene regulation, which seems to be mediated through at least two A element-like cis-motifs in the gene promoter.

Amyloid↗