Role of xenoreactive natural antibodies in pig-to-human lung xenotransplantation.
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ABO Blood-Group System↗
Biomedical subjects
H Kato
Publications and source records attributed to H Kato.
MHC restriction in contact hypersensitivity to dicyclohexylcarbodiimide.
Mouse ear swelling tests were performed using different strains of mice with dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), di-p-tolylcarbodiimide (DTC), and positive control chemicals, such as dinitrochlorobenzene (DNCB) and oxazolone (OXA). The chemicals were examined at different doses up to the minimal irritating concentration determined in a irritancy assay. While BALB/c mice exhibited strong responses for the carbodiimide compounds, C3H/HeN mice demonstrated no reactions. Other strains, C57BL/6 and DBA/1, also showed responses to DCC, but CBA/J mice with the same haplotype as C3H/HeN (H-2(k)) did not. Based on our present findings, there may be a specific unresponsiveness to DCC dependent on the H-2(k) haplotype.
Animals↗
Cooperativity between extracellular adenosine 5'-triphosphate and activation of N-methyl-D-aspartate receptors in long-term potentiation induction in hippocampal CA1 neurons.
The mechanism of ATP-induced long-term potentiation (LTP) was studied pharmacologically using guinea-pig hippocampal slices. LTP, induced in CA1 neurons by 10 min application of 10 microM ATP, was blocked by co-application of the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (5 or 50 microM). In ATP-induced LTP, the delivery of test synaptic inputs (once every 20 s) to CA1 neurons could be replaced by co-application of NMDA (100 nM) during ATP perfusion. These results suggest that, in CA1 neurons, a co-operative effect between extracellular ATP and activation of NMDA receptors is required to trigger the process involved in ATP-induced LTP. In addition, ATP-induced LTP was blocked by co-application of an ecto-protein kinase inhibitor, K-252b (40 or 200 nM), whereas a P2X purinoceptor antagonist, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid 4-sodium (50 microM), or a P2Y purinoceptor antagonist, basilen blue (10 microM), had no effect.The results of the present study, therefore, indicate that the mechanisms of ATP-induced LTP involve the modulation of NMDA receptors/Ca(2+) channels and the phosphorylation of extracellular domains of synaptic membrane proteins, one of which could be the NMDA receptor/Ca(2+) channel.
2-Amino-5-phosphonovalerate↗
Enhancement of bonding strength by graded structure at interface between apatite layer and bioactive tantalum metal.
Tantalum metal is a candidate for use as an implant material in high load-bearing bony defects, due to its attractive features such as high fracture toughness and high workability. This metal, however, does not have bone-bonding ability, i.e. bioactivity, and therefore the development of bioactive tantalum metal is highly desirable. It is known that the essential prerequisite for an artificial material to show bioactivity is to form a bonelike apatite layer on its surface in the body environment. The same type of apatite layer is formed in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with 0.5 M-NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously formed the same apatite after a long soaking period. In the present study, the bonding strength of the apatite layer to the substrate was quantitatively evaluated in comparison with that to the untreated tantalum metal. Adhesive strength was measured as an estimation of bonding strength, and the surface microstructure of both the substrates was characterized in order to discuss the difference in the bonding strength in terms of surface structure. The apatite layer formed on the NaOH- and heat-treated tantalum metal shows higher adhesive strength than that formed on the untreated metal. The amorphous sodium tantalate layer formed on the tantalum metal by NaOH and heat treatments, has a smooth graded structure where its concentration gradually changes from the surface into the interior metal. Smooth graded structure with complex of apatite is constructed after soaking in SBF. The higher bonding strength of the apatite layer formed on the treated metal is attributed to its smooth graded structure.
Journal Article↗
Therapeutic effect of neuronal nitric oxide synthase inhibitor (7-nitroindazole) against MPTP neurotoxicity in mice.
Effects of neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole), nonselective NOS inhibitor (N(G)-nitro-L-arginine methyl ester; L-NAME), and monoamine oxidase inhibitor (pargyline) were studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP at 1-h intervals. A significant depletion in dopamine and DOPAC concentration was observed in the striatum from 1 day after MPTP treatment. The pretreatment of 7-nitroindazole and pargyline, but not L-NAME, dose-dependently protected against MPTP-induced depletion in dopamine content 3 days after MPTP treatment. Our histochemical study also showed that 7-nitroindazole and pargyline can prevent a marked decrease in the nigral cells and a marked increase in astrocytes in striatum 7 days after MPTP treatment. The protective effect of 7-nitroindazole against MPTP-induced dopamine and DOPAC depletion in the striatum was not attenuated by intraperitoneal pretreatment with L-arginine. Furthermore, the posttreatment of 7-nitroindazole or pargyline protected against MPTP-induced depletion of dopamine content. These results demonstrate that the protective mechanism by which 7-nitroindazole counteracts MPTP neurotoxicity in mice may be due not only to inhibition of nNOS, but also to MAO-B inhibition. Furthermore, our study suggests that the posttreatment of 7-nitroindazole and pargyline can prevent a significant decrease in dopamine levels in the striatum of MPTP-treated mice. These findings have important implications for the therapeutic time window and choice of nNOS or MAO inhibitors in patients with Parkinson's disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Molecular basis of the alteration in skin collagen metabolism in response to in vivo dexamethasone treatment: effects on the synthesis of collagen type I and III, collagenase, and tissue inhibitors of metalloproteinases.
BACKGROUND: Glucocorticoids are widely used for the treatment of various diseases, despite known side-effects such as skin atrophy. Many studies have shown that the status of collagen fibres in the skin is affected by glucocorticoid treatment. However, the molecular mechanism underlying the alteration of collagen metabolism in the skin by glucocorticoid treatment remains unknown. OBJECTIVES: To characterize the molecular mechanisms related to the deterioration of the dermis in response to glucocorticoids, the status of two major types of collagen, collagenase, and tissue inhibitors of metalloproteinases (TIMPs) in the dorsal skin of rats was studied at the protein and mRNA levels. METHODS: Samples of rat dorsal skin were obtained after daily (1 mg kg-1) subcutaneous injections of dexamethasone (DEX) for 8 days. mRNA levels of two types of collagen and of TIMPs were measured by a lysate RNase protection assay. mRNA levels of collagenase were measured by a quantitative polymerase chain reaction. Protein levels of collagen and collagenase were measured by an immunoblot analysis. RESULTS: Levels of type I tropocollagen and type III tropocollagen were drastically reduced in response to DEX. The effects of DEX treatment were more severe on type III than type I collagen: it also produced a significant decrease in fibril collagen of type III collagen. DEX treatment was found to decrease both active and latent forms of collagenase as well as its mRNA levels. Among TIMPs, mRNA levels of TIMP-1 and TIMP-2 were decreased in response to DEX treatment, whereas those of TIMP-3 were not affected. CONCLUSIONS: These results suggest that DEX treatment strongly interferes with both the synthesis and degradation of type I collagen and, more drastically, type III collagen, the molecule that is known to play a major role in the initiation of wound healing. The present study may provide a molecular basis for the deterioration of skin function, impaired wound healing, and skin atrophy caused by glucocorticoid treatment.
Animals↗
Fetal gastric size in normal and abnormal pregnancies.
OBJECTIVE: The aim of this observational study was to construct an ultrasound index of fetal gastric size for the prenatal detection of congenital digestive tract obstruction. SUBJECTS: A total of 386 fetal measurements were performed in routine ultrasonographic examinations of women with normal singleton pregnancies between 18 and 39 weeks of gestation. Gastric measurements were also performed in 13 fetuses with digestive tract obstruction. METHODS: The ultrasound plane which included the pylorus and which provided the largest stomach area was used for definition and measurement of gastric area and maximal longitudinal dimension. The transverse section at the center of the gastric corpus was used for transverse and anteroposterior dimensions. Gastric volumes were calculated as a prolate ellipsoid. The gastric area ratio was defined as the gastric area divided by the transverse abdominal area. Biparietal diameter (BPD) and abdominal transverse area were also measured. RESULTS: The fetal gastric area was significantly correlated with fetal gastric volume (r = 0.91) and gestational age (r = 0.74). However, the correlation coefficient for gastric area with gestational age was smaller than those of the BPD (r = 0.97) with gestational age and abdominal transverse area with gestational age (r = 0.97). Gastric area ratio decreased slightly towards term. The gastric area ratio was below the 95% confidence intervals for the predicted values in all five fetuses with esophageal atresia, and exceeded the 95% confidence intervals in seven of the eight fetuses with duodenal atresia or intestinal tract obstruction. CONCLUSION: Fetal gastric area correlates with ultrasound-determined gastric volume measurements and appears to be useful in the assessment of digestive tract anomalies.
Case-Control Studies↗
Prenatal diagnosis of congenital epulis: a case report.
Congenital epulis or congenital granular cell tumor, is a benign tumor that has rarely been diagnosed prenatally. We report a case of a large congenital epulis diagnosed at 26 weeks of gestation that increased in size during gestation. Color and power Doppler ultrasound examination showed marked blood flow in the tumor. The tumor could be resected completely following Cesarean section and histologically examined. We discuss the prenatal diagnosis and histogenesis of congenital epulis.
Adult↗
Analyses of serum lipoprotein(a) and the relation to phenotypes and genotypes of apolipoprotein(a) in type 2 diabetic patients with retinopathy.
To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.
5' Untranslated Regions↗
Intracerebroventricular injection of glucagon-like peptide-1 decreases monoamine concentrations in the hypothalamus of chicks.
1. We measured the concentrations of dopamine (DA), norepinephrine (NE), epinephrine (E) and 5-hydroxytryptamine (5-HT) in the hypothalamus of 21-d-old male brown-egg layer-type chicks after intracerebroventricular injection of glucagon-like peptide-1 (GLP-1). 2. The monoamine concentrations of the whole hypothalamus, paraventricular nucleus and lateral hypothalamic area were not significantly affected by GLP-1. 3. However, concentrations of DA, NE and E, but not 5-HT, in the ventromedial hypothalamic nucleus (VMH) were significantly decreased by GLP-1. 4. These observations suggest that the anorexigenic effect of GLP-1 involves catecholaminergic systems in the VMH in the chick.
Animals↗
Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions.
AIM: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: Thirty-three patients with KD, including group A patients (n = 22) who had no CALs and group B patients (n = 11) who had CALs, as well as age-matched febrile (n = 10) and afebrile controls (n = 11), were studied. RESULTS: Peak plasma E-selectin levels (172.0 +/- 58.6 ng ml(-1)) occurred during the acute phase of KD, while peak plasma P-selectin levels (260.3 +/- 43.2 ng ml(-1)) occurred during the subacute phase of the illness (p<0.05). Plasma L-selectin levels (1757.3 +/- 244.3 ng ml(-1)) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E- (225.1 +/- 46.8 ng ml(-1)) and P-selectin (259.4 +/- 76.2 ng ml(-1)) of patients with CALs (n = 11) were significantly higher than those of patients (n = 22) with no CALs (E-selectin, 131.6 +/- 36.9 ng ml(-1); P-selectin, 184.9 +/- 84.6 ng ml(-1); p < 0.05). When a plasma E-selectin value before immunoglobulin treatment of >184.7 ng ml(-1) was used as the cut-off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis. CONCLUSION: Higher plasma levels of E-selectin may have potential as a predictor of the incidence of coronary artery lesions in Kawasaki disease patients.
Child↗
Quantitative evaluation of the changes in plasma concentrations of cardiac natriuretic peptide before and after transcatheter closure of atrial septal defect.
UNLABELLED: The purpose of this study was to investigate the changes in plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD) during transcatheter closure of defects. The plasma concentrations of ANP and BNP were obtained from 14 patients with ASD at before closure, and at 5 min, 24 h, 1 mo and 3 mo after transcatheter ASD closure using an Amplatzer septal occluder. Ten healthy children aged 6-18 y were studied as controls. All ASDs were successfully closed. Compared with control values (mean +/- SD, 17 +/- 6.8 ng 1(-1), ANP concentrations before closure were significantly elevated (24 +/- 9.8ng 1(-1), p < 0.05). ANP concentrations increased significantly at 5 min after closure (34 +/- 18 ng 1(-1), p < 0.05) compared with preclosure concentrations. At 24 h after closure, the concentrations decreased to values not different from control values (19 +/- 11 ng 1(-1), p = ns). BNP levels before closure (19 +/- 9.9 ng 1(-1) were also elevated significantly compared with control values (12 +/- 4.9ng 1(-1), p < 0.05). BNP concentrations increased significantly at 5 min after closure (23 +/- 14 ng 1(-1), p < 0.05) compared with preclosure concentrations. ANP values at 24 h were lower than at 5 min after closure, whereas BNP values were higher (32 +/- 11 ng 1(-1), p < 0.05). As with ANP, the concentrations gradually decreased to values not different from control values at 3 mo after the procedure (12 +/- 6.3 ng 1(-1), p = ns). CONCLUSION: Plasma concentrations of ANP and BNP may become effective markers for evaluating changes in cardiac load after transcatheter ASD closure.
Adolescent↗
Gamma-aminobutyric acidA and benzodiazepine receptor alterations in the rat brain after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle.
Gamma-aminobutyric acidA (GABA(A)) and benzodiazepine (BZ) receptors and dopamine uptake sites in 6-hydroxydopamine-treated rat brains were studied by receptor autoradiography using [3H]muscimol, [3H]flunitrazepam and [3H]mazindol binding, respectively. The rats were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks post-lesion. Degeneration of the nigrostriatal pathway after 6-hydroxydopamine treatment caused a significant loss of dopamine uptake sites in the ipsilateral striatum and substantia nigra (SN) in the lesioned animals. In the contralateral side, however, dopamine uptake sites showed no significant changes in the brain throughout the experiments. On the other hand, no significant changes in GABA(A) receptors were observed in the brain of both the ipsilateral and contralateral sides during post-lesion. In contrast, BZ receptors were observed significantly increased in the ventromedial part of striatum of the ipsilateral side from 2 to 4 weeks post-lesion. Furthermore, a transient increase in BZ receptors was found in the ipsilateral SN only at 2 weeks post-lesion. In contralateral side, most regions examined showed no significant changes in BZ receptors throughout the experiments except for a transient increase in the SN at 1 week post-lesion. These results demonstrate that 6-hydroxydopamine can cause severe functional damage in dopamine uptake sites in the nigrostriatal pathway. Our results also suggest that the change in BZ receptors is more pronounced than that in GABA(A) receptors in the brain after 6-hydroxydopamine treatment. Furthermore, our findings suggest that the increase in BZ receptors in the brain of 6-hydroxydopamine-treated model may be due to the additional disruption of the nigrostriatal dopamine system. Thus, investigations into possible changes in neurotransmitter receptors other than dopaminergic receptors appear to be important for the elucidation of pathogenesis of Parkinsons disease.
Animals↗
Role of nitric oxide synthase against MPTP neurotoxicity in mice.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic pathway injury similar to that observed in Parkinson's disease. Many hypotheses have been proposed to explain the mechanisms underlying MPTP neurotoxicity. Previous work showed that the inhibitor of neuronal nitric oxide synthase (nNOS) might produce protection against MPTP-induced dopaminergic toxicity. To exactly test the role of NO in MPTP neurotoxicity, we examined the effect of nNOS inhibitor 7-nitroindazole, in comparison with that of nonselective NOS inhibitor (L-NAME), immunosuppressant (FK-506), monoamine oxidase (MAO) inhibitors (clorgyline and pargyline), N-methyl-D-aspartate receptor antagonist (MK-801) and Ca2+ antagonist (amlodipine). Among seven compounds, 7-nitroindazole produced dose-dependent protection against MPTP-induced depletion of striatal dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in mice. Clorgyline and pargyline also showed a significant effect on MPTP-induced dopamine depletion in the mouse striatum. However, both compounds did not protect against MPTP-induced depletion of striatal DOPAC Our immunohistological study with tyrosine hydroxylase (TH) and microtuble-associated protein 2 (MAP 2) showed that 7-nitroindazole or pargyline can protect against MPTP-induced depletion of TH and MAP 2 immunostained neurons in the substantia nigra. Furthermore, these compounds reduced a marked increase in GFAP-positive astrocytes of the mouse striatum after MPTP treatments. The present study demonstrates that nNOS inhibitor 7-nitroindazole as well as MAO inhibitors clorgyline and pargyline can produce dose-dependent neuroprotection against the dopaminergic neurotoxicity of MPTP. However, nonselective NOS inhibitor L-NAME, immunosuppressant FK-506, NMDA receptor antagonist MK-801 and Ca2+ antagonist amlodipine did not show a beneficial effect on MPTP neurotoxicity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Radial osteotomy for late-stage Kienböck's disease. Wedge osteotomy versus radial shortening.
We have reviewed 20 patients with stage-IIIB and stage-IV Kienböck's disease in order to examine the efficacy of two forms of radial osteotomy, namely radial wedge osteotomy and radial shortening. Lateral closing wedge osteotomies and radial shortenings were carried out on 11 and nine patients, respectively. There were no preoperative differences with respect to age, gender, and radiological stage. After a mean follow-up of 29 months, all patients, in both groups, had either a good or an excellent outcome. After the lateral closing wedge osteotomy, the radioscaphoid angle significantly increased and the Ståhl index significantly decreased. Progression of the degenerative changes at the radioscaphoid joint was found in two patients in this group. By contrast, there were no significant changes in any radiological parameters after radial shortening. Both procedures gave acceptable clinical results in stage-IIIB and stage-IV Kienböck's disease.
Adolescent↗
Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy.
Immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), was performed on human endometrium obtained from patients with normal menstrual cycles, patients given oestrogen and progesterone, and women in early pregnancy. Intense immunostaining of VEGF was observed in both glandular epithelial and stromal cells during the mid-secretory phase; the immunostaining intensity was increased by administration of oestrogen plus progesterone and strong immunostaining was observed in decidual cells of early pregnancy. In addition to the immunostaining in vascular endothelial cells, strong KDR immunostaining was observed in glandular epithelial cells and in decidualized stromal cells induced by administration of oestrogen plus progesterone, whereas flt-1 immunostaining was negligible. Strong immunostaining for flt-1 and KDR was found in both vascular endothelial cells and decidual cells in early pregnancy. Endometrial stromal cells isolated from proliferative phase endometrium were incubated with oestrogen (10(-8) mol l-1) and medroxyprogesterone acetate (MPA; 10(-6) mol l-1) for 18 days to study the regulation of VEGF, flt-1 and KDR in endometrial stromal cells by oestrogen and progesterone. Expression of VEGF and KDR mRNAs was increased significantly by oestrogen and MPA, accompanied by decidualization, whereas flt-1 mRNA expression was not affected. In conclusion, VEGF and its receptors may play important roles in implantation and maintenance of pregnancy.
Adult↗
[Maintaining safety management in the field of surgery].
Due to an increase in the number of medical accidents and medical conflicts, the administration of medical safety has recently introduced the following measures to cope with this situation; the process and the structure (reason) of error is analyzed based upon evidential facts, the origin of the errors is analyzed mainly in terms of teamwork and specialized medicine and structures rather than in terms of the ability of the individual, and the strategy against medical errors has been converted from aspects of management to prevention. The comprehensive strategy pursued now covers the field of social medical systems in addition to medical institutions. However, the judicial decisions in 90% of medical conflicts ruled that these were caused by the lack of knowledge and skills of the medical doctor, and a survey performed by the Japan Medical Association based on medical insurance research has reported incidences of repeated medical errors by the same physician. This has led to some criticism from the victim's viewpoint that insufficient administration of medical quality result in increased numbers of accidents which are due to repeated medical errors, under "legal" medical practice by "incompetent" doctors who should have been systematically reeducated or dismissed. In recent years, several societies and research groups of the Ministry of Health, Labour and Welfare have constructed medical guidelines based on evidence-based medicine techniques. The introduction of the clinical pathway offers the medical team access to information, directed to the appropriate roles, which may be helpful in performing constant safety checks. This medical check method that involves the patient's input will also contribute to the prevention of medical errors and promotion of safety.
Critical Pathways↗
Cystic adventitial disease of the popliteal artery. Etiologic considerations.
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Cysts↗