Case report: Mucocele of the tip of the appendix.
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Biomedical subjects
Publications and source records attributed to T Furukawa.
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To clarify the mechanism of cellular injury through the nonenzymatic reaction of glucose with proteins, we studied the cytotoxic effect of glycated bovine serum albumin on cultured smooth muscle cells in the presence of cupric ion. Glycated proteins were prepared by incubating bovine serum albumin with 0.5 M D-glucose in 0.3 M sodium phosphate buffer at 37 degrees C for 2, 4 and 16 weeks (g-BSA-2, g-BSA-4 and g-BSA-16, respectively). Early glycation products, such as fructosamine, were formed more than two weeks after incubation. However, the immunoreactivity of glycated proteins to anti-AGE antibody was 12-fold higher in g-BSA-16 than in g-BSA-2. Both g-BSA-2 and g-BSA-16 showed a concentration-dependent cytotoxicity in smooth muscle cells in the presence of 80 microM cupric ion by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) dye reduction assay and dye exclusion test. Flow cytometry and spectrofluorophotometry using dihydrorhodamine 123 showed that the extracellular generation of oxidants was dose-dependently enhanced with increasing concentrations of g-BSA-2 or g-BSA-16 in the presence of cupric ion. However, no difference was observed in the intracellular generation of oxidants between the presence and absence of glycated proteins by flow cytometry using 2', 7'-dichlorofluorescein diacetate. Cytotoxicity and oxidant generation were prevented by catalase and tiron, but not by superoxide dismutase or mannitol, a hydroxyl radical scavenger. These results indicate that smooth muscle cells may be damaged by reactive oxygen species which are produced extracellularly by the interaction with the early glycation products and cupric ion, and suggest that hydrogen peroxide may be a candidate for reactive oxygen species which contribute to such oxidative damage of smooth muscle cells.
The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is an uncommon neuromuscular disorder caused by mitochondrial dysfunctions that result in headaches, seizures, and progressive dementia. The authors describe a clinical case study of gastrointestinal manifestations in a pedigree with MELAS, in which all three children, ages 11, 8, and 6, demonstrated acute onset of intestinal obstruction. They unexpectedly showed severe abdominal distension and vomiting. Their parents had no clinical manifestation. The first female sibling underwent an emergent laparotomy because she was diagnosed to have intestinal strangulation. She had postoperative complications caused by progressive lactic acidosis and died the next day. The second and third sisters had similar onsets of the disease and were treated with gastrointestinal decompression and intravenous administration of lactate-free fluid and coenzyme Q10. Genetic testing using blood samples showed an A-to-G point mutation at nucleotide position 3243 in the tRNALeu(UUR) region in the mitochondrial DNA. In MELAS children who demonstrate acute onset of gastrointestinal manifestations, a careful review of family history and an elevation of serum lactate and pyruvate levels may enable a differential diagnosis to be made of acute abdomen to avoid unnecessary surgical intervention.
Chromatic aspects of receptive field size in the H1 horizontal cell syncytium of the carp retina were investigated using spectral photostimuli (blue or red) presented in the form of either a pair of a small spot and annulus, or a narrow moving slit. In the light-adapted retina, the receptive field for the blue stimulus was found to be significantly smaller than that for the red, i.e. there was a chromatic difference in the receptive field size. During the course of dark adaptation, the overall receptive field size increased, but the chromatic difference decreased. Immediately after adaptation to bright light, the receptive field sizes were reduced significantly, but the chromatic difference increased, mainly due to a greater reduction in the receptive field for the blue stimulus. Application of dopamine (5 microM) to a dark-adapted retina gradually decreased the receptive field size for both colours, but the chromatic difference became larger, again due to a greater reduction in the receptive field size for the blue stimulus. 2-Amino-4-phosphonobutyrate (APB) applied to light-adapted retinae at a working concentration of 1 mM, greatly expanded the receptive field size and suppressed the chromatic difference due to the effect being greater for the receptive field for the blue stimulus. The effect of APB was slow and cumulative. On the other hand, intracellular injection of cGMP or dibutyryl-cGMP increased the chromatic difference in the receptive field size. It is suggested (i) that the chromatic difference in the receptive field size could be due to a cGMP-coupled, conductance-decreasing receptor mechanism activated by APB; and (ii) that the mechanism is associated with short-wavelength sensitive cone input to the H1 cells and operates in the light-adapted state of the retina.
Photoreceptors provide an excellent model for studies of vertebrate neuronal differentiation, and many human diseases resulting in blindness primarily affect photoreceptors. There is therefore great interest in studying the cellular and molecular mechanisms of photoreceptor development. This article discusses our current understanding of this process, including the recent discovery of the homeodomain transcription factor Crx and its potential role in diseases affecting human vision.
Ancestral longevity is sometimes thought to contribute to psychosocial well-being in late life. The present paper aims to examine if parental longevity is associated with mental health among the elderly. The age at death of the parents was compared between 68 patients with major depression who were aged 65 or over and 40 subjects of the same age range without any history of psychiatric disorder. Cox regression revealed that the fathers of the elderly men with unipolar depression died at a significantly younger age than those of the control group. Several hypotheses are advanced to explain this unexpected and intriguing association.
AIMS: The present study was performed to evaluate whether echocardiographic assessment of end-diastolic wall thickness and myocardial fatty acid metabolic single-photon emission tomographic imaging with 123I-beta-methyl-iodophenyl pentadecanoic acid could be used to predict the reversibility of dysfunctional left ventricular segments after coronary artery revascularization. METHODS AND RESULTS: Twenty-eight patients with wall motion abnormalities related to stenosed coronary arteries underwent resting two-dimensional echocardiography and 123I-beta-methyl-iodophenyl pentadecanoic acid single photon emission tomography before coronary angioplasty. A dysfunctional segment was considered viable by the presence of either preserved wall thickness (> or = 75% of the thickness of a normal segment) or preserved fatty acid uptake (> or = 50% of that in normal region). Echocardiography was repeated after successful angioplasty. Functional recovery was observed in 32 (74%) of 43 hypokinetic and nine (100%) of nine akinetic segments with preserved wall thickness and in 11 (79%) of 14 thinned akinetic segments with preserved fatty acid uptake. In contrast, no functional recovery was observed in any of the 13 thinned segments with < 50% fatty acid uptake (eight akinetic and five dyskinetic). Using combined evaluation of both methods, positive and negative predictive values for post-revascularization functional outcome were 79% and 100%, respectively, in all dysfunctional segments; and 87% and 100%, respectively, in akinetic/dyskinetic segments. CONCLUSIONS: The present study showed that echocardiographic findings of preserved wall thickness and single-photon emission tomography evaluated preserved fatty acid uptake in thinned segments are reliable predictors of post-revascularization functional recovery and the concordant absence of both accurately predict negative outcome.
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RATIONALE AND OBJECTIVES: Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) was injected intravenously for magnetic resonance imaging in patients with impaired renal function, and the permeabilities of two types of general hemodialysis (HD) membrane to this agent were compared. METHODS: One of the HD membranes, Nipro FB-210-U membrane (U membrane), has a larger pore size than the other, Nipro FB-210-M membrane (M membrane). On the same day as magnetic resonance imaging was performed, the patient underwent a 4-hour HD session. Blood was sampled before and at five points after the start of HD. RESULTS: Mean dialysance of Gd-DTPA was 175.8 to 185.8 mL/min with the U membrane and 120.5 to 130.1 mL/min with the M membrane. The elimination rate was 91.1% with the U membrane and 81.1% with the M membrane 4 hours after the start of HD. The permeability was significantly higher with the U membrane than with the M membrane. CONCLUSION: Although it is more expensive, the U membrane should be chosen rather than the M membrane for HD to remove Gd-DTPA from the body as efficiently as possible.
Although MS-551 is classified as a class III antiarrhythmic agent (K+ channel blocker), its effect on the Na+ channel has not been fully characterized. We investigated the effect of MS-551 on the Na+ current (I(Na)) in isolated guinea pig ventricular myocytes. MS-551 blocked I(Na) in a concentration-dependent manner at a holding potential of -140 mV. The concentration-response curve revealed that the median inhibitory concentration (IC50) for the block of resting channel was 292 +/- 20 microM with a Hill coefficient of 1 (n = 11). Although MS-551, 300 microM, did not show a use-dependent block, it shifted the steady-state inactivation curve in a hyperpolarizing direction by 6.3 +/- 0.8 mV and delayed the recovery process from long depolarization. This delay was considered to be related to the drug unbinding and was expressed by a triple exponential function. The slowest component had a time constant of 409 +/- 35 ms, and the proportion of the amplitude of this component to the total current amplitude was 14 +/- 3% (n = 6). The IC50 for the inactivated Na+ channel was thus estimated to be 169 microM at maximum. These results suggest that MS-551 has a low affinity for both the resting and inactivated Na+ channel.
To pursue the pathogenesis of endometrial carcinogenesis, we investigated microsatellite instability, mutations in the PTEN, TGF beta RII, IGFIIR, and BAX genes, and LOHs on 10q in 18 putative endometrial premalignant lesions (11 endometrial atypical hyperplasias (ATHs), 2 complex hyperplasias, and 5 simple hyperplasias) as well as 8 endometrial cancers (ECs). In the ATH cases, MSIs as well as LOHs at 10q were observed at frequencies similar to those in ECs. Mutations in PTEN, BAX, and IGFIIR were observed only in ATHs and ECs. These results suggest that (1) PTEN, BAX, and IGFIIR are already mutated in ATHs, and (2) ATH is one of the precursor lesions which could lead to EC.
Intraductal ultrasonography (IDUS) was performed on 22 patients with extrahepatic bile duct cancer, using the percutaneous transhepatic approach. Intraductal ultrasonography images of the proximal invasion of the bile duct cancer were defined. In addition, three patients were examined through the peroral approach, to try to diagnose whether or not the cancer invaded to the bifurcation of the hepatic duct. Intraductal ultrasonography images obtained through the percutaneous approach could be classified into three patterns, types 1, 2 and 3, according to the features of the interior surface of the bile duct and the thickness of the bile duct wall. Type 1 images, which did not show protrusions into the bile duct lumen and had a bile duct wall of even thickness, were not likely to show bile duct cancer. Type 2 images showed protrusions of the tumour into the bile duct lumen and the surfaces of the protrusions were irregular. Type 3 images showed single or multiple low echoic papillary masses in the bile duct. Using the peroral technique, we considered all three cases to be type 1 and could diagnose that cancer had not invaded to the bifurcation of the hepatic ducts. From the results of this study, we suggest that proximal invasion of extrahepatic bile duct cancer can be diagnosed using IDUS.
We describe a 27-month-old boy who was first admitted to our hospital on 7 January 1995 with nasal bleeding. From 6 months of age he has had lymphadenopathy, low levels of serum uric acid, increased levels of serum lactate dehydrogenase and hyper gamma-globulinemia. From the age of 18 months he has had persistent Epstein-Barr virus (EBV) infection (target cells; B cells), recurrent episodes of thrombocytopenia, anemia and hepatosplenomegaly. Dysmobility of the left leg and arm from a central nervous system complication during a relapse with pancytopenia on March 1995, was also observed. Relapses of thrombocytopenia with increases of platelet-associated immunoglobulin G and hepatosplenomegaly have been observed approximately every 2 months, and two relapses of pancytopenia were accompanied with weak positivity of Coombs test and low level of haptoglobin. These recurrent episodes were improved with prednisolone. However, now in June 1997 we have not been able to diagnose what underlies the above clinical symptoms, except that the patient has a persistent EBV infection.
There have been many studies in the literature examining childhood parental loss as a risk factor for adult psychiatric disorders such as depression, schizophrenia or anxiety disorders. However, with regard to alcohol dependence, only a limited number of such studies exists, and these have reported inconsistent findings. The present paper aims to examine the relationship between early parental loss and subsequent development of alcohol dependence among Japanese men. We directly interviewed 75 men with alcohol dependence (according to DSM-III-R), who were visiting 23 psychiatric hospitals and clinics all over Japan, and 52 healthy controls without any lifetime psychiatric diagnosis, drawn from a general population. When stratified for sex and age, there was no statistically significant difference between the patients and the controls in the rates of maternal or paternal death or separation before the age of 16 years. These findings and the review of the literature suggest that the relationship between childhood parental loss and alcohol dependence is not a straightforward one.
The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with RBP-J. Differential splicing gave rise to two transcripts of the KyoT gene, KyoT1 and KyoT2, that encoded proteins with four and two LIM domains, respectively. With differential splicing resulting in deletion of an exon, KyoT2 lacked two LIM domains from the C terminus and had a frameshift in the last exon, creating the RBP-J-binding region in the C terminus. KyoT1 had a negligible level of interaction with RBP-J. Strong expression of KyoT mRNAs was detected in skeletal muscle and lung, with a predominance of KyoT1 mRNA. When expressed in F9 embryonal carcinoma cells, KyoT1 and KyoT2 were localized in the cytoplasm and the nucleus, respectively. The binding site of KyoT2 on RBP-J overlaps those of EBNA2 and Notchl but is distinct from that of Hairless, the negative regulator of RBP-J-mediated transcription in Drosophila. KyoT2 but not KyoT1 repressed the RBP-J-mediated transcriptional activation by EBNA2 and Notch1 by competing with them for binding to RBP-J and by dislocating RBP-J from DNA. KyoT2 is a novel negative regulatory molecule for RBP-J-mediated transcription in mammalian systems.
In the Xenopus oocyte heterologous expression system, the electrophysiological characteristics of rabbit ClC-2 current and its contribution to volume regulation were examined. Expressed currents on oocytes were recorded with a two-electrode voltage-clamp technique. Oocyte volume was assessed by taking pictures of oocytes with a magnification of x 40. Rabbit ClC-2 currents exhibited inward rectification and had a halide anion permeability sequence of Cl- > or = Br- >> I- > or = F-. ClC-2 currents were inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), diphenylamine-2-carboxylic acid (DPC), and anthracene-9-carboxylic acid (9-AC), with a potency order of NPPB > DPC = 9-AC, but were resistant to stilbene disulfonates. These characteristics are similar to those of rat ClC-2, suggesting rabbit ClC-2 as a counterpart of rat ClC-2. During a 30-min perfusion with hyposmolar solution, current amplitude at -160 mV and oocyte diameter were compared among three groups: oocytes injected with distilled water, oocytes injected with ClC-2 cRNA, and oocytes injected with ClC-2 delta NT cRNA (an open channel mutant with NH2-terminal truncation). Maximum inward current was largest in ClC-2 delta NT-injected oocytes (-5.9 +/- 0.4 microA), followed by ClC-2-injected oocytes (-4.3 +/- 0.6 microA), and smallest in water-injected oocytes (-0.2 +/- 0.2 microA), whereas the order of increase in oocyte diameter was as follows: water-injected oocytes (9.0 +/- 0.2%) > ClC-2-injected oocytes (5.3 +/- 0.5%) > ClC-2 delta NT-injected oocytes (1.1 +/- 0.2%). The findings that oocyte swelling was smallest in oocytes with the largest expressed currents suggest that ClC-2 currents expressed in Xenopus oocytes appear to act for volume regulation when exposed to a hyposmolar environment.
DUSP6 (alias PYST1), one of the dual-specificity tyrosine phosphatases, is localized on 12q21, one of the regions of frequent allelic loss in pancreatic cancer. This gene is composed of three exons, and two forms of alternatively spliced transcripts are ubiquitously expressed. Although no mutations were observed in 26 pancreatic cancer cell lines, reduced expressions of the full-length transcripts were observed in some cell lines, which may suggest some role for DUSP6 in pancreatic carcinogenesis.