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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 307 records · Page 17Linked to original sources

Development of an assay for bioactive insulin.

A method to detect the biological activity of serum insulin has been developed. This method, called a bioactive insulin assay, determines the ability of serum insulin to stimulate the autophosphorylation of insulin receptors in an intact cell system. For this, intact Chinese hamster ovary cells which overexpress the human insulin receptor are treated with serum and then lysed. Autophosphorylation of the insulin receptors is then measured by a two-site immunofluorometric assay using monoclonal anti-insulin receptor antibodies and europium-labeled anti-phosphotyrosine antibodies. The detection limit of this assay is 1 microU/ml of insulin. Dilution and recovery test inter- and intraassay coefficient variations are permissible. The amount of insulin determined by this assay correlated well with the amount of insulin detected by a traditional immunological assay for insulin (r = 0.94, P < 0.001). In the case of a mutant insulin, the insulin from a Wakayama subject, the biologically active insulin was found to constitute 9% of the immunologically reactive insulin. Since this assay specifically measures the amount of biologically active insulin present in serum, it should be particularly useful in monitoring active insulin in patients with various mutant insulins.

Animals↗

Soluble Fas in the serum of patients with non-Hodgkin's lymphoma: higher concentrations in angioimmunoblastic T-cell lymphoma.

The soluble form of Fas (sFas) can block apoptosis induced by the Fas ligand in vitro. A recent report demonstrated that mice injected with sFas displayed autoimmune features. Therefore, an elevated serum concentration of sFas may be associated with lymphoproliferation and autoimmune diseases. We measured the serum concentrations of sFas in 77 patients with non-Hodgkin's lymphoma (NHL) [8 angioimmunoblastic T-cell lymphoma (AIL), 12 T-cell NHL, 53 B-cell NHL, and 4 natural killer-cell NHL]. Elevated concentrations of sFas were detected only in AIL, which is frequently accompanied by autoimmune diseases (P < 0.005 compared with age-matched controls). A possible association of sFas and autoimmune features in AIL is discussed.

Aged↗

Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block.

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.

Aged↗

New guiding catheter for transrad PTCA.

A new guiding catheter for PTCA is described. In our department, 302 patients (405 lesions) underwent transradial coronary angioplasty using the 6 Fr Kimny guiding catheter since January 1996. The total engagement rate using the Kimny guiding catheter was 91.3% (370/405). The engagement rate after the modified Kimny guiding catheter was introduced in May 1996 increased to 96.0% (243/253). The stent delivery success rate was 98.4%. We had two dislodged stents. PTCA for both left and right coronary arteries in a single procedure with the Kimny guiding catheter was performed via the radial artery in 27 patients. In 24 of these patients (89%) we engaged both coronaries successfully. In the remaining 3 patients we switched to another catheter. Except for 4 patients with non-Q-wave myocardial infarction, no major cardiac complications were encountered. No major entry site-related complications were seen, and no patient required vascular surgery or blood transfusions. In one patient the Kimny guiding catheter tip caused a minor dissection of the LMT, but no ischemic event occurred as a result. In conclusion, the Kimny device is a useful PTCA guiding catheter for routine angioplasty and stenting.

Aged↗

Expression of an Xist promoter-luciferase construct during spermatogenesis and in preimplantation embryos: regulation by DNA methylation.

Dosage compensation for X-linked genes in mammals is accomplished by inactivating one of the two X chromosomes in females, a process involving a regulatory gene, Xist (X-inactive specific transcript). Xist maps to the X-inactivation centre and is expressed from the inactive X chromosome in female somatic cells and at the time of X inactivation during spermatogenesis in the male. In female preimplantation embryos, Xist demonstrates imprinting in that the paternal allele inherited from the sperm is preferentially expressed. This preferential paternal Xist expression is correlated with paternal X inactivation in the extraembryonic lineages at the blastocyst stage. We have analysed a 233-bp Xist promoter fragment (nt -220 to +13) for its ability to direct appropriate expression and its regulation by DNA methylation. This minimal promoter sequence directs expression of the luciferase reporter gene following injection of the construct into one-cell embryos. In vitro methylation of the construct before injection represses transcription. In six different transgenic lines, expression of the Xist promoter-luciferase transgene occurs only in the testis of the males (as for the endogenous Xist gene). The testis-specific expression is correlated with hypomethylation of the transgene, although to different extents in different lines. Following paternal transmission, expression of the Xist promoter-luciferase construct in preimplantation embryos is correlated with degree of hypomethylation in the testis and the degree of hypomethylation of the transgene in embryos at the morula stage. It is concluded that the patterns of methylation of the transgene in sperm (and in microinjected transgenes) can regulate the activity of the Xist promoter in the preimplantation embryo and thus support the hypothesis that gametic methylation patterns govern imprinted expression of the endogenous Xist gene in development.

Animals↗

Plasticity of Drosophila paired function.

The Drosophila Paired (Prd) transcription factor has homeodomain (HD) and paired domain (PD) DNA-binding activities required for in vivo function. Correspondingly, Prd activation of late even-skipped (eve) expression occurs through a conserved target sequence (PTE) with HD and PD half sites, both of which are required for activation. To investigate the relationship between the HD and PD, and their roles in conferring specificity to Prd function, we tested altered versions of the Prd protein and of the PTE target site using in vivo assays in embryos. We found that function through PTE was constrained by the targeting specifications of both the HD and PD as well as the spatial relationship between these two domains. PTE function was also constrained by the spacing between the target half sites for the PD and HD, although surprisingly, late eve activation was retained when PTE was replaced by in vitro optimized binding sites for either the PD alone or for an HD dimer. In contrast to late eve regulation, other Prd targets tolerated more changes in the Prd protein, suggesting that their target sequences may be qualitatively different from PTE.

Animals↗

[Near-infrared spectroscopy during hypothermic selective cerebral perfusion--a clinical study of its value].

The purpose of this study is to assess the value of near-infrared spectroscopic oxymetry (NIRO) in monitoring cerebral oxygenation and metabolism during selective cerebral perfusion (SCP) for surgery of the aortic arch. The measurement protocol during SCP comprised oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and total hemoglobin levels in the brain. From March 1994 through March 1997, 14 patients underwent surgical treatment of the aortic arch anomalies with intraoperative monitoring with NIRO. The temporary circulatory arrest was accomplished at a rectal temperature of 22 degrees C and the hypothermic SCP was employed for the cerebral protection. SCP was initiated at a flow rate of 10 ml/kg/min so as to maintain HbO2 at the same level as immediately before the circulatory arrest (baseline). The longitudinal changes of HbO2 level during the process revealed four different patterns and were grouped accordingly. Three of the patients maintained HbO2 level above the baseline during SCP (Group A). HbO2 level reached to the baseline at initial flow rate but decreased gradually thereafter in 4 patients (Group B). Gradual increment of the perfusion flow rate failed to elevate HbO2 level to the baseline in the 5 patients (Group C1). In this group, HbO2 level started to elevate about 60 minutes after the initiation of SCP. HbO2 level of the remaining 2 patients was absolutely resistant to the increment of SCP flow rate and kept low values throughout SCP (Group C2). All the patients recovered uneventfully without any neurological abnormality. Our analyses for the longitudinal behavior of the HbO2 level confirmed the previously reported evidences that the values were affected not only by perfusion flow rate but also by hemodilution, blood transfusion, and perfusion pressure. Furthermore, our present study disclosed another evidence that HbO2 level was strongly affected by subclavian steal phenomenon. Although there were no differences in the clinical outcome among the groups, referring to the theories that HbO2 level is better not to be departed from baseline level, it could be concluded that HbO2 level monitoring in the setting of the determined hematocrit and hypothermia was effective for securing the adequate demand and supply balance of the cerebral oxygenation. Our conclusion may extend further that NIRO is a useful means in determining the optimal perfusion flow rate of SCP during surgery of the aortic arch.

Aged↗

[Surgical repair of isolated congenital tricuspid regurgitation with artificial chordae--a case of two year-follow up].

Isolated congenital tricuspid regurgitation derived from primary dysplasia of the valvular apparatus is a rare cardiac abnormality. A 23-year-old woman was first diagnosed to have an isolated tricuspid regurgitation during infancy and was followed up at our hospital. She developed progressive cardiomegaly at the age of 22 years. The chest roentgenogram at the time of admission revealed marked cardiomegaly with a cardiothoracic ratio of 64%. Despite the severe regurgitation of the tricuspid valve, the catheter examination disclosed v and mean pressures of the right atrium of 9 mmHg and 5 mmHg, respectively. The operative findings revealed a markedly dilated tricuspid annulus of 45 mm in diameter (157% of normal) and fragile and redundant valve leaflets, anterior leaflet in particular. Anterior papillary muscle was absent without any vestige thereof. Chordae tendinae of the anterior and posterior leaflets were absent and those of the septal leaflet were attached to the ventricular septum. Each commissure was tethered to the ventricular wall by thick and short chordal tissue. The chordal abnormalities were repaired by four artificial chordae of 4-0 ePTFE suture and an annuloplasty with Carpentier-Edwards ring (36 mm) was added. She recovered uneventfully and was discharged on postoperative day 30. A follow-up echocardiography at 2 years after surgery showed excellent function and trivial regurgitation of the valve. No evidences of thrombus or calcification of the artificial chordae were detected. This experience draws us to conclude that the artificial chordal replacement is one of the useful surgical options for the repair of isolated congenital tricuspid regurgitation.

Adult↗

Apoptosis and PCNA expression induced by prolactin in structural involution of the rat corpus luteum.

There are two stages of luteal regression. The first stage is functional regression that is characterized by a decreased production of progesterone secretion; the second stage of structural involution is referred to as a structural luteolysis. In rodents, prolactin has a biphasic action on the corpus luteum. It is luteotrophic, but when exposed to functionally regressed corpora lutea it causes luteolysis. The objective of the present studies was to examine mechanisms of prolactin action in structural luteolysis, whether apoptosis is involved in this process, and to examine the possible association of cell proliferation signals as mediators of structural luteolysis. Prolactin-induced structural luteolysis was associated with apoptosis verified by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). Apoptotic cells made up about 3% of the cells 24 hours after the first injection of prolactin, a level that remained constant at all stages of structural luteolysis. Total ovarian weight and DNA content were decreased about 50% in 72 hours after induction of structural luteolysis by prolactin, The finding of about 3% of cells in apoptosis indicates apoptosis is a rapid process. Proliferating cell nuclear antigens (PCNA) of luteal cells were significantly decreased during functional luteal regression, but were conversely increased in structural luteolysis as shown by western blotting and immunohistochemistry. In general PCNA expression is reported to be decreased during structural involution, and there are no reports that have linked excess expression of PCNA with apoptosis and structural luteolysis. We speculate that an excessive increase in expression of PCNA which signals activation of cell proliferation creates a disorder in the signals involved with DNA synthesis. This disorder results in mitotic catastrophe and in the induction of apoptosis. Therefore the disorder of cell cycle signals in luteal cells are associated with prolactin induced apoptosis in structural luteolysis.

Animals↗

Concurrent enchondroma and periosteal chondroma of the humerus mimicking chondrosarcoma.

A case of concurrent enchondroma and periosteal chondroma of the right proximal humerus in a 19-year-old woman is reported. Radiographs and CT scans showed a periosteal lesion with saucerization and spicula-like mineralization of the lateral aspect of the right proximal humerus and an ill-defined irregular lucency with stippled calcifications of the medullary cavity adjacent to it. MRI showed a long intramedullary lesion in addition to the surface lesion. There was no cortical disruption by imaging and gross examination. Histologically, both lesions showed benign cartilaginous tumors; concurrent enchondroma and periosteal chondroma of the humerus was therefore diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Radiographic features may be confused with chondrosarcoma.

Adult↗

Characterization of the cells in the repair tissue of full-thickness articular cartilage defects.

It is well established that a full-thickness articular cartilage defect is repaired with a fibrocartilaginous tissue, cells of which are derived from undifferentiated mesenchymal stem cells in the bone marrow. To characterize the repair cells biochemically, full-thickness defects were created in rabbit knee joints and the repair tissues taken at 3, 6, and 12 weeks after surgery. The repair cells were cultured and examined biochemically to investigate the effects of four exogenous growth factors with regard to the metabolism of type II collagen and proteoglycans. A significant increase of carboxy-terminal type II procollagen peptide production was observed in the conditional medium of the repair cells, especially taken at 6 weeks after surgery, in the presence of each growth factor. Glycosaminoglycan content was also increased and proteoglycan synthesis stimulated. The repair cells taken at the early stage of the repair process could originally have more activity of type II collagen synthesis, and the growth factors used could enhance the differentiation of the repair cells in vitro.

Animals↗

Light- and electron-microscopic study of the distribution of axons containing substance P and the localization of neurokinin-1 receptor in bone.

Substance P (SP) is a neuropeptide that is released from axons of sensory neurons and causes signal transduction through the activation of the neurokinin-1 receptor (NK1-R). The present study demonstrates the distribution of SP-like-immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly found near the trabecular bone in the temporal bone marrow, but they were only sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1-Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive products of NK1-Rs were distributed close to the plasma membrane. At the electron-microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole cytoplasm, except for the clear zone of the osteoclasts, and in pit-like structures along the plasma membrane. The NK1-R-immunoreactive structures in the cytoplasm were divided into two types of organelles, consisting of vesicular and vacuolar structures (probably transport vesicles and early endosomes). In the osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was fewer than in the osteoclasts. These results thus suggest that SP secreted by the sensory axons could directly modulate bone metabolism via NK1-Rs.

Animals↗

Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation.

BACKGROUND: Significant mitral regurgitation (MR) is protective against left atrial (LA) spontaneous echo contrast formation that is associated with an increased thromboembolic risk. However, the effects of MR on the risk of stroke in patients with nonrheumatic atrial fibrillation (AF) have been unknown. We studied whether or not MR was associated with a decreased risk of stroke in patients with nonrheumatic AF. METHODS: We performed an observational analysis of retrospectively collected data on 290 patients with nonrheumatic AF. Left atrial diameter (LAD) and the degree of MR were estimated by transthoracic echocardiography. Risk factors for stroke were assessed by univariate and multivariate analyses. The mean follow-up was 7.4 years. RESULTS: Among these patients, 68 had a stroke during the follow-up (rate of stroke per year of follow-up 3.2%). In 95 patients with LAD of > or =48 mm, the incidence of stroke (9%) in the severe MR group (moderate or severe, n=43) was significantly lower than that (25%) of the mild MR group (none, trivial, or mild; n=52) (chi-square=3.95, p=0.047). The relative risk of stroke for increase in MR from mild to severe groups, for every 10 mm increment in LA size, for sex, and for every increase of 10 years of age was 0.45 (95% CI, 0.20 to 0.97), 1.06 (95% CI, 0.75 to 1.49), 0.98 (95% CI, 0.55 to 1.72), and 1.33 (95% CI, 1.04 to 1.71), respectively. CONCLUSIONS: In patients with nonrheumatic AF, age was an independent predictor of an increased risk of stroke, and MR may be protective against stroke, especially in those patients with LA enlargement.

Adult↗

Surgical management of isolated congenital tricuspid regurgitation.

BACKGROUND: Isolated congenital tricuspid regurgitation without downward displacement of the leaflet is a rare clinical entity. Degenerative cusps and lack of chordae may preclude valvuloplasty and require valve replacement. METHODS: Three consecutive patients with isolated congenital tricuspid regurgitation underwent surgical repair between May 1995 and April 1997. Their ages were 23, 15, and 8 years old. Tricuspid valvuloplasty was feasible in all of them, with use of a gathering suture of the anterior leaflet, artificial chordae implantation, and ring annuloplasty. RESULTS: All 3 patients survived and recovered well after the operation. The cardiothoracic ratios on their chest roentgenograms decreased from 0.64 to 0.52 in patient 1, from 0.58 to 0.48 in patient 2, and from 0.60 to 0.44 in patient 3. Postoperative echocardiograms showed competent tricuspid valves and the disappearance of regurgitation in all cases. CONCLUSIONS: Although malformation of the valve is extensive in isolated congenital tricuspid regurgitation, application of artificial chordae with conventional valvuloplasty technique can avoid the use of prosthetic valves by establishing the competence of the tricuspid valve.

Adolescent↗

Substrate specificity of THCA-CoA oxidases from rat liver light mitochondrial fractions on dehydrogenation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid CoA thioester.

The substrate specificity of rat liver peroxisomal 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA (THCA-CoA) oxidases, which catalyze the dehydrogenation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) CoA thioester, having an asymmetric center at C-25, to form (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid (delta 24-THCA) CoA thioester, was studied. The stable isotope labeled substrates, [3,7,12-18O3]-(25R)- and (25S)-THCA CoA thioesters were synthesized by an exchange reaction of carbonyl oxygens on a steroid nucleus of 3,7,12-trioxo-5 beta-cholestanoic acid, followed by metal hydride reduction and condensation reaction with CoA. After incubation of a mixture of unlabeled (25R)- and 18O-labeled (25S)-THCA CoA thioester, or vice versa, with hepatic peroxisomal THCA-CoA oxidases, biotransformed delta 24-THCA was determined by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. The delta 24-THCA was derived only from (25S)-THCA CoA thioester, indicating that the 25S epimer of THCA is a preferential substrate on dehydrogenation by THCA-CoA oxidases.

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