Biomedical subjects
Publications and source records attributed to S Kamei.
A patient with clinical features consistent with pulmonary embolism showed no improvement despite therapy with tissue-plasminogen activator and full-dose heparin. Transvenous catheter suction biopsy was successful in establishing an antemortem histologic diagnosis of primary pulmonary artery leiomyosarcoma. Urgent surgical intervention was performed.
Thirty-seven chronically unstable ankles in thirty-six patients were operated on with use of a Watson-Jones tenodesis. Thirty-four ankles (thirty-three patients) were followed for a mean duration of thirteen years and eight months (range, ten to eighteen years) after the operation. There were nine male and twenty-four female patients. The mean age of the patients was thirty-one years (range, fourteen to fifty-seven years) at the time of the operation and forty-four years (range, twenty-eight to seventy years) at the time of the latest follow-up. At the time of the most recent follow-up evaluation, twenty-seven patients (twenty-eight ankles) were examined directly by one of us and twenty-five patients (twenty-six ankles) also were evaluated radiographically. The other six patients were interviewed, with use of a questionnaire, by telephone. Of the thirty-four ankles, nineteen had an excellent result (grade 1), eleven had a good result (grade 2), three had a fair result (grade 3), and one had a poor result (grade 4) according to the rating system of Good et al. The mean score (and standard deviation) on the ankle-hindfoot scale of the American Orthopaedic Foot and Ankle Society for the twenty-eight ankles that were examined directly by one of us was 90 +/- 9.3 points (range, 68 to 100 points). Progression of an exostosis at the edge of the joint was detected in eighteen (69 percent) of the twenty-six ankles that were examined radiographically, but narrowing of the joint space was not seen in any ankle. No relationship was detected between the clinical results and radiographic osteoarthrotic changes or the duration of follow-up. The results did not deteriorate over the long term.
A 55-year-old man had rhabdomyolysis and myocardial damage induced by palytoxin. Weakness and myalgia of four extremities occurred five hours after eating a fish. Rhabdomyolysis developed and the serum creatine phosphokinase (CK) was elevated to 40,000 IU/l on the 3rd day. Gastric lavage with activated charcoal and forced mannitol-alkaline diuresis therapy were performed. The patient recovered with no complication such as renal failure. In this case, palytoxin was suggested to induce myocardial damage which was demonstrated by an elevation of the myosin light chain level and a change in electrocardiogram.
A phosphate-containing polymer was covalently immobilized onto a polyethylene (PE) rod, a poly(ethylene terephthalate) (PET) thread, and a PET film by a surface graft polymerization technique, followed by immersion in calcium phosphate solution to deposit a thin hydroxyapatite (HA) layer on the modified polymer surfaces. The PE rod had a tapered shape, while the PET thread was fixed with clips after implantation, both to minimize the micromovement which may occur in bone. The PE rod was implanted through press-fitting in the femur of rat. Significant enhancement was observed for direct contact of the implant surface with a newly formed bone for both the grafted only and the further HA-deposited PE rods in comparison with the untreated PE at 4, 5, and 6 weeks after implantation. The rats implanted with the modified PET thread in the femur were sacrificed 3 and 6 weeks after implantation. Statistically significant differences were observed for the untreated versus the grafted plus HA-deposited rods at 6 weeks after implantation. To study the resorption of the deposited HA on the methacryloyloxyethylene phosphate-grafted surface, HA-deposited PET films were subcutaneously implanted in the back of rats. The deposited HA was rapidly resorbed within 3 weeks of implantation. These results suggest that the phosphate polymer chains grafted on the PE and PET surfaces effectively induced nucleation and growth of HA crystals. It seems likely that the thin HA layer additionally deposited in vitro onto the grafted PE and PET surfaces was resorbed rapidly and then promoted the growth of HA crystals in vivo.
Recently, we found N1,N8-diacetylspermidine (Ac2Spd) and N1,N12-diacetylspermine (Ac2Spm) in human urine, and noted that their amount increased significantly in patients with urogenital malignancies. Previous findings that simultaneous reference to these diacetylpolyamines is useful in distinguishing cancer patients from healthy persons were confirmed by more recent analytical data on urine samples from several cancer patients. Further examination revealed that urinary Ac2Spm and Ac2Spd tended to decrease when cancer patients were treated and entered partial remission. In cases where the Ac2Spm and Ac2Spd levels were normal or near-normal after treatments, the prognosis of the patients was generally good. In contrast, when their level remained far above the normal limits after apparently effective treatment, the prognosis of the patients was poor. When a patient is in remission for more than 3 years, urinary levels of both Ac2Spm and Ac2Spd are stabilized and stay below the normal limits, with rare exceptions. The recurrence of a cancer as well as the complication of a second one during the period of follow-up examination was accompanied by elevation of urinary diacetylpolyamines. These observations indicate that urinary Ac2Spm and Ac2Spd are useful as prognostic indicators after treatment and during follow-up examination of cancer patients.
We have applied non-radioactive polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) to the detection of gene mutations causing Fabry disease. Nineteen of 22 known mutations were detected as electrophoretic mobility shifts on PCR-SSCP analysis. Then, DNA from newly diagnosed Japanese patients with the classical form of Fabry disease was subjected to PCR-SSCP analysis, and 4 novel mutations (1 small deletion, 1 nonsense mutation and 2 missense mutations) and 1 neutral polymorphism were identified. Furthermore, identification of an asymptomatic heterozygote and a hemizygote with moderate clinical manifestations was successfully achieved by application of this method to a family with the variant form of Fabry disease. PCR-SSCP is useful for the gene diagnosis of etiologically heterogeneous Fabry disease.
N8-Acetylspermidine was coupled to mercaptosuccinylated BSA using a bifunctional cross-linker, N-(4-maleimidobutyryloxy)succinimide, and the resulting conjugate was used to raise N1,N8-diacetylspermidine (DiAcSpd)-specific antibodies in rabbits. DiAcSpd-specific antibodies were enriched from crude sera through a series of affinity-based fractionations using ligands with structures mimicking those of DiAcSpd and monoacetylspermidines. With the N8-acetylspermidine-BSA conjugate as a solid phase antigen in a competitive ELISA system, the selectivity for DiAcSpd over other polyamine species was high, but competition by DiAcSpd added to the fluid phase was too weak for the system to be applicable to measurement of the concentration of DiAcSpd in human urine. In contrast, with the N1-acetylspermidine-BSA conjugate adsorbed on the ELISA plate, DiAcSpd efficiently competed for the same antibody, thus yielding a sensitive competitive ELISA system for measuring DiAcSpd. The Ki value for DiAcSpd with the latter competitive ELISA system was 54 nM, and the cross-reactivity with DiAcSpd, N1,N12-diacetylspermine, N8-acetylspermidine, N1-acetylspermidine, and acetylputrescine was 100, 1.2, 0.74, 0.12, and 0.08%, respectively. The DiAcSpd-specific antibodies and the competitive ELISA system developed in this study will prove to be useful for analyzing the urinary level of DiAcSpd, that was recently shown to be a promising diagnostic and prognostic indicator of malignant disorders.
To evaluate the annual incidence of viral CNS infections in Japan, a questionnaire was delivered to the related departments of hospitals and an answer was given from 377 departments (30.2%). Etiological analysis of patients with viral meningoencephalitis indicates that the most (64%) among those with encephalitis diagnosed, is herpes simplex virus (HSV) encephalitis, and the most (89%) among those with viral meningitis diagnosed is non-polio enterovirus (EV) meningitis, followed by mumps virus (MV) meningitis (9%). Epidemiological findings of CNS infections with three viruses, HSV, EV, and MV, are different from each another in age distribution or in seasonal and epidemic incidence, similar to European and American findings, except that with Japanese encephalitis virus (JEV). Infections with JEV decrease recently to 2-39 cases/year by control measures for many years in Japan, though the infections with JEV continue to occur in continental Asian countries. In addition to JE, Japanese travellers abroad should be treated to be protected from infectious diseases absent in Japan, such as rabies.
The very rapid clearance of human recombinant tissue factor pathway inhibitor (h-rTFPI) may result from its binding to vascular proteogly can and LDL receptor-related protein (LRP). To investigate the effect of factor Xa on the clearance of h-rTFPI, we developed a specific ELISA for h-rTFPI/factor Xa complex, and compared the pharmacokinetic parameters of h-rTFPI/factor Xa complex and the clearance rate of the cellular proteogly can-associated h-rTFPI/factor Xa complex with those of h-rTFPI by itself in rabbits. We found that the h-rTFPI/factor Xa complex disappeared from circulation at a rapid rate of clearance, having pharmacokinetic parameters similar to those of non-complexed h-rTFPI. After the rapid disappearance of the h-rTFPI complex from plasma, an intravenous injection of heparin resulted in a release of h-rTFPI/factor Xa complex into plasma. However, the recovery of heparin-releasable h-rTFPI/factor Xa decreased significantly in a time-dependent manner. Therefore, we examined the half-life of proteogly can-associated h-rTFPI/factor Xa and determined it to be 51 min, which was significantly shorter than that of h-rTFPI by itself (107 min). These results suggest that a complex formation of h-rTFPI with factor Xa promotes a clearance of proteogly can-associated h-rTFPI existing in the liver and kidney.
Bilateral striatal necrosis in acute encephalopathy has been reported in a small number of adults with methanol or cyanide intoxication, hypoxic encephalopathy or haemolytic-uraemic syndrome. Acute encephalopathy with bilateral striatal necrosis has been reported in infants and children. However, the pathogenesis of the necrosis remains unclear. This is the first report of serial imaging from the very early to chronic stage in two acute encephalopathic adults with bilateral striatal necrosis. A clinicoradiological study is presented for clarification of the pathological process and pathogenesis. Striatal lesions were not detected in the very early stages, but only thereafter. Serial studies suggested that the lesions were caused by delayed neuronal death. These patients had severe lactic acidosis, near the limit for survival. There have been few reports of adults with acute encephalopathy and bilateral striatal necrosis in whom arterial pH was described; all these exhibited marked acidosis. The common pathophysiological condition among these encephalopathies with bilateral striatal necrosis could be lactic acidosis elicited by impairment of ATP generation through the Krebs cycle. The striatum might represent one of the target areas of Krebs-cycle blockade.
Four alpha-galactosidase gene mutations were identified in Japanese male patients with Fabry disease who had no detectable alpha-galactosidase activity. Two of them were novel mutations, an 11-bp deletion in exon 2 and a g-1 to t substitution at the 3' end of the splice acceptor site in intron 1. The former caused a frameshift and led to the creation of a new stop codon at codon 118. The latter was predicted to provoke aberrant mRNA splicing followed by accelerated degradation of the mRNA. A nonsense mutation, R301X, and a 2-bp deletion starting at nucleotide position 718, which were reported previously, were also identified in unrelated patients.
This is the first report on the evaluation of treatment with fasudil hydrochloride, a novel intracellular calcium antagonist, for wandering symptoms in patients with cerebrovascular dementia by using 31P-magnetic resonance spectroscopy (MRS) and Xe-computed tomography (CT). The subjects studied were two patients with cerebrovascular dementia who had had frequent wandering episodes. The clinical diagnosis was Binswanger-type cerebral infarction in patient 1 and sequelae of cerebral bleeding and multiple lacunar infarctions in patient 2. Treatment with fasudil at 30 or 60 mg/day was given orally for 8 weeks. The wandering symptoms disappeared in both patients during the treatment and reappeared a few days after discontinuation of the treatment. Mental tests indicated that memory was mildly improved during the treatment. Pretreatment 31P-MRS findings revealed decreases in relative signal intensities of phosphomonoester and phosphodiesters and an increase in that of mean adenosine triphosphates. After treatment, these findings disappeared. The regional cerebral blood flow values by Xe-CT in both patients did not show significant changes from before treatment to the values after treatment. These results suggest that the efficacy of fasudil for the wandering symptoms and mental function observed in our patients may have been related to a direct effect on intracellular energy metabolism.
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We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.
Reconstruction of the mobile tongue needs soft and thin tissue not to disturb tongue movement, and therefore a free forearm flap has usually been used for this kind of reconstruction. However, it entails a cosmetic problem, especially for young people. We have detained good results with tongue reconstructions using free dorsalis pedis flaps. The donor site of the dorsalis pedis flap is inconspicuous. The dorsalis pedis flap is thin (even among obese persons), has a long vessel pedicle, and stable blood supply. In cases of head and neck reconstruction, two teams can easily operate simultaneously. This flap is not as large as a forearm flap but it is large enough for hemitongue reconstruction. We measured the thickness of the soft tissue of both the dorsalis pedis and the forearm among obese volunteers. Dorsalis pedis was not as thick as the forearm.
Case 1 had undergone surgery for antrum stenosis 20 years earlier as well as subsequent surgery with reconstruction by Billroth II for carcinoma occurring at the anastmotic site. Case 2 had undergone partial resection of the jejunum for injury of the intestine. Case 3 had undergone reconstruction of the thoracic esophagus using the stomach following excision of carcinoma. For these 3 cases, reconstruction using a free jejunal flap was performed and no disturbance was observed at the donor site. These results strongly suggest that reconstruction using a free jejunal graft be used in patients with a history of previous gastro-intestinal surgeries, with careful observation before and during surgery.
The photosynthetic reaction center (RC) complex that forms a homodimer of core and cytochrome c subunits was isolated from Chlorobium limicola f. thiosulfatophilum, strain Larsen. The complex showed only two subunit bands at 68 (PscA core) and 21 kDa (cytochrome c551) on SDS-PAGE analysis, indicating the complete deletion of the light-harvesting bacteriochlorophyll a (BChl a) protein as well as the iron-sulfur protein. It contained 27 +/- 3 molecules of BChl a, 7 +/- 1 Chl-670, 3 +/- 1 carotenoids, and 1.6 +/- 0.1 c-type hemes per the primary electron donor P840. The complex showed a light-induced charge separation and recombination between P840 and the acceptor Chl-670 at 77 K as follows: P840*Chl-670-->P840+Chl-670(-)-->P840TChl-670-->P84 0 Chl-670. Pigment compositions and their function in the (PscA/cytochrome c551)2 complex were studied by absorption, circular dichroism, and fluorescence spectroscopy.
The effect of galactose on alpha-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the alpha-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose.