Drug-related low responsiveness to recombinant human erythropoietin therapy in three patients with end-stage renal disease.
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Biomedical subjects
Publications and source records attributed to Y Ohtsuka.
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Two total lower lip reconstructions were accomplished by combining a radial forearm free flap and a depressor anguli oris muscle transfer. The radial forearm flap was used to reconstruct the inner surface of the lower lip. The bipedicled musculofascial flap, which includes both depressor anguli oris muscles, the depressor labii inferioris muscles, and the mentalis muscles, was elevated onto the chin and sutured superiorly to the modioli to obtain innervated sphincter function. Good results were obtained both aesthetically and functionally. Electromyography revealed almost normal mobility of the depressor anguli oris muscles 6 months after the operation. No drooling was seen during mastication, and no air leakage was observed during puffing of the cheeks. This is an effective procedure for the reconstruction of the sphincter function of the lower lip.
BACKGROUND: It is believed that the incidence of cystic fibrosis (CF) among Asiatic races, including the Japanese, is very rare. This epidemiological study was carried out to investigate the incidence of CF in Japan. METHODS: We collected literature describing CF cases among pure Japanese and found 124 cases reported as CF during the 43 years from 1951, when the first case was reported, to 1993. Only 104 cases (57 male and 47 female patients) of 124 cases met our diagnostic criteria. RESULTS: A simple calculation based on the number of reported CF cases and of live births after 1980 suggested that the incidence of CF is about 1 in 350,000 in the Japanese population. Twenty-nine (27.9% of the total) of 30 patients diagnosed in the neonatal period presented symptoms of meconium ileus, an incidence higher than that reported for the white population. CONCLUSIONS: Our study results suggest that the incidence of CF in the Japanese population is even rarer than had been estimated before and that there is a genetic difference between northern European and Japanese populations.
The thin calcium-phosphate (Ca-P) coatings produced by the ion-beam-mixing method instead of the plasma-spraying method have been found to be amorphous, resulting in films that easily dissolved in simulated body fluid. These coatings crystalized with conventional heat treatment in an electric furnace but tended to crack easily. Therefore, the purpose of this study was to find a suitable heat treatment that controls the solubility of Ca-P coatings without weakening their adhesion to titanium (Ti) substrate. Thin coatings (approximately 1 microm) were coated onto Ti substrates, followed by heat treatment in a conventional furnace and rapid heating by infrared radiation and laser radiation. X-ray diffraction analysis revealed untreated films to be amorphous but to become crystalline after being heated in a furnace at 500 degrees C, heated rapidly with infrared radiation higher than 600 degrees C and with laser radiation at output power of 10W. We evaluated solubility by estimating the film thickness after immersion in simulated body fluid for 5 weeks: Untreated films dissolved within 1 day. Coatings treated with infrared radiation at 600 degrees C dissolved minimally. Cracks were observed in coatings subjected to infrared radiation at 800 degrees C and furnace-heated at 500 degrees C. Coatings treated with laser radiation tended to dissolve easily, with non-uniform surface degradation. X-ray photoelectron spectroscopy analysis at the interface between the coating and the Ti substrate showed that cracks were the result of decreased Ca-implanted layers and too much growth of Ti-P compounds. No difference was recognized in the Ti-oxidation state among specimens. These data indicate that rapid, homogeneous, and comparatively low-temperature heating, such as defocused infrared radiation, controls Ca-P solubility and ensures the adherence of the coatings to the substrate.
Mucosal damage is commonly observed in food-sensitive enteropathy in infants, and the generation of leukotrienes is involved in the pathogenesis of this enteropathy. Because supplementing n-3 fatty acids is known to modify the production of leukotrienes, we investigated whether a change of dietary fatty acid composition affects leukotriene synthesis and food hypersensitivity reactions in the intestine by using a mouse model of food-sensitive enteropathy. The model was prepared by feeding ovalbumin to BALB/c mice after intraperitoneal injection of cyclophosphamide. Diets were prepared from soybean oil (control), perilla oil, lard, corn oil, and 0.125 volume of corn oil (low fat diet) and given to mice for 4 wk. Villous heights, crypt depths, leukotriene B4 and C4 production in the intestine were measured. Crypt hyperplasia and villous atrophy were severer in the corn oil-fed group than those of control group, whereas mucosal damage in the perilla oil and low fat diet groups was minimal. In the corn oil-fed group, red blood cell membrane levels of n-3 fatty acids were lower than the control, and the synthesis of leukotrienes was highest among all groups. In the perilla oil and low fat diet groups, n-6 fatty acids were lower than those of control group and leukotriene production was significantly suppressed. These results indicate that reducing cell membrane levels of n-6 fatty acids by feeding less n-6 fatty acids or supplementing n-3 fatty acids, is important to suppress leukotriene biosynthesis for prevention from mucosal damage in food-sensitive enteropathy.
During development of the ascidian Halocynthia roretzi, the tadpole larva hatched from the tailbud embryo metamorphoses to the adult with a body wall muscle. Although the adult body wall muscle is morphologically nonsarcomeric smooth muscle, it contains a troponin complex consisting of three subunits (T, I, and C) as do vertebrate striated muscles. Different from vertebrate troponins, however, the smooth muscle troponin promotes actin-myosin interaction in the presence of high concentration of Ca2+, and this promoting property is attributable to troponin T. To address whether the embryonic/larval tail striated muscle and the adult smooth muscle utilize identical or different regulatory machinery, we cloned troponin T cDNAs from each cDNA library. The embryonic and the adult troponin Ts were encoded by distinct genes and shared only < 60% identity with each other. These isoforms were specifically expressed in the embryonic/larval tail striated muscle and the adult smooth muscle, respectively. These results may imply that these isoforms regulate actin-myosin interaction in different manners. The adult troponin T under forced expression in mouse fibroblasts was unexpectedly located in the nuclei. However, a truncated protein with a deletion including a cluster of basic amino acids colocalized with tropomyosin on actin filaments. Thus, complex formation with troponin I and C immediately after the synthesis is likely to be essential for the protein to properly localize on the thin filaments.
The activity of mammalian topoisomerase I is inhibited by acidic phospholipids. We investigated the effect of psychotropic drugs and local anesthetics on cardiolipin-inhibited calf thymus DNA topoisomerase I activity. Chlorpromazine, promethazine, and imipramine, which interact with phospholipids, suppressed the inhibitory effect of cardiolipin. The present results suggest that relaxation of DNA supercoiling is involved in the cytotoxic action of these drugs.
We report here the transient relaxation of plasmid DNA by inhibitors of DNA gyrase in Escherichia coli. Relaxation of plasmid DNA in the presence of nalidixic acid, an inhibitor of the A subunit of DNA gyrase, lasted less than 60 min. The effect of nalidixic acid was not observed in a nalA26 mutant, a strain resistant to nalidixic acid due to a mutation in the gyrA gene. Novobiocin, whose target is the B subunit of DNA gyrase, also caused transient DNA relaxation. Resupercoiling of relaxed DNA in the presence of nalidixic acid was inhibited by pretreatment of the cells with chloramphenicol. As mutations of both the rpoH and recA genes did not affect the resupercoiling reaction, this step seems to require protein synthesis that is independent of both heat shock and SOS responses.
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We studied the relationship between the effectiveness of corticosteroid pulse treatment, clinical characteristics and outcomes in 17 patients with acute exacerbatin of idiopathic interstitial pneumonia. Acute exacerbation was defined as a decrease in PaO2 by more than 10 Torr, worsening of chest-radiographic findings, and deterioration of symptoms within 1 month. Effects of corticosteroid pulse treatment were judged 2 weeks and 3 months after the end of treatment. The change in AaD2 was computed and was used to determine whether the treatment had been effective, temporarily effective, or ineffective. The effects at three months were difficult to predict on the basis of those at two weeks. The treatment was often effective in patients who had not previously received steroids and in those with mild disease. Those in whom the treatment was effective at three months lived longer after the exacerbation than did those in whom it was ineffective, but the average lengths of survival through the whole clinical course were not significantly different among the three groups. We suggest that corticosteroid pulse treatment is effective in acute exacerbatins of idiopathic interstitial pneumonia and that effectiveness should be evaluated three months after treatment.
Pulp tissue loss of the fingers was repaired with arterialized venous flaps from the thenar or hypothenar regions in 13 patients. Thirteen of the 15 flaps transferred survived completely. The thenar and hypothenar skin is durable and of appropriate texture for replacement of finger pulp defects. An average flap size of 2 x 3 cm was adequate for repairing the tissue loss of the fingers. These are not sensory flaps. However, they exhibited useful sensory recovery within 6 months of the operation. This method is simple and results in minimal donor-site morbidity. The arterialized venous flap is thus a useful alternative for the repair of finger pulp tissue losses.
Helicobacter pylori (H. pylori) has been shown to stimulate secretion of IL-8, a CXC-chemokine, from gastric epithelial cells, and this process is important in the induction of gastric mucosal inflammation associated with H. pylori infection. However, considering the biological effects and target cells, CC-chemokines may also be playing an important role in H. pylori-associated gastritis. In the present study, we investigated the expression of IL-8 (CXC-chemokine), MCP-1 (CC-chemokine), and RANTES (CC-chemokine) in human gastric mucosa by RT-PCR analysis. The positive rates of IL-8, MCP-1, and RANTES in 35 patients were 68.5%, 80%, and 80% respectively, suggesting the possible importance of CC-chemokines. We next examined the production of MCP-1 by MKN28 gastric epithelial cells. MKN28 cells were found to secrete MCP-1 in response to IL-1 beta or TNFalpha in a dose- and time-dependent manner. Quantitative RT-PCR analysis showed the induction of MCP-1 mRNA by these proinflammatory cytokines. Co-culture with H. pylori also induced the expression of MCP-1 mRNA. These results suggest that gastric epithelial cells secrete CC chemokine MCP-1 in response to proinflammatory cytokines and H. pylori, and this process may also be important in the chronic gastric inflammation associated with H. pylori infection.
A 50-year-old man presented with asymptomatic gross hematuria which he had first noticed 3 months earlier. Clinical examinations revealed a non-papillary, broad-based tumor on the left lateral wall of the urinary bladder with a clinical stage of T3N0M0. The pathological diagnosis of a transurethral biopsy tissue specimen was small cell carcinoma. Neoadjuvant intraarterial infusion chemotherapy using cisplatin and adriamycin was initially administered but proved to be ineffective. Thus, we performed a radical cystectomy. The tumor tissue was apparently homogenous and composed of small cells arranged in sheets and solid patterns, and was staged to be pT3bR1L2V0N0. An electron microscopic study confirmed small cell carcinoma with neurosecretory granules. Postoperatively, 4 courses of adjuvant chemotherapy consisting of cisplatin, etoposide and ifosfamide were administered. The patient is alive without any evidence of tumor recurrence 26 months after the operation.
It is generally accepted that residual renal function remains well-preserved longer with CAPD than with hemodialysis. However, consideration and impact of the contributory effects of residual renal function on the adequacy of renal replacement therapy has not been well defined. In this report, creatinine clearance (Ccr), Kt/V, normalized protein catabolic rate (nPCR) and urinary excretion of uremic solutes were studied in 26 stable CAPD patients with a four-bag exchange. Weekly Ccr, weekly Kt/V and nPCR were 62.3 +/- 20.2 l/week/1.73 m2, 1.77 +/- 0.35, and 0.90 +/- 0.13 g/kg/day, respectively. These parameters correlated significantly with the daily urine volume. The weekly Ccr and Kt/V of anuric patients seemed to be inadequate. Urinary excretion of urea nitrogen, Cr, Na, Cl, Pi and beta 2-microglobulin (beta 2-MG) were dependent upon the daily urine volume. Significant phosphorus and beta 2-MG excretion seemed to have an effect on the prevention of bone and joint complications, because serum iPTH and beta 2-MG levels increased after the patients fell into an anuric state. It was suggested from this study that CAPD should be started before the patient loses residual renal function because four bag exchange as the standard CAPD prescription might not be adequate once the patient loses urine excretion.
In current psychiatric therapy, two or more kinds of antipsychotic drugs are usually prescribed in Japan. However, there are few data on the therapeutic plasma concentrations of antipsychotic drugs or on the correlation between the daily dose and the plasma concentration, in cases where several antipsychotic drugs had been prescribed for each patient. We measured the therapeutic plasma concentrations of 9 antipsychotic drugs in 24 psychiatric inpatients during a 6-month period. They were treated with fixed dosages of antipsychotic drugs. Plasma samples were collected early in the morning once a month, and the concentrations of antipsychotic drugs were determined by gas chromatography with nitrogen phosphorus detection, high-performance liquid chromatography (HPLC) with fluorescence detection and HPLC with UV detection. The plasma levels of chlorpromazine, levomepromazine, thioridazine, haloperidol, bromperidol, zotepine, oxypertine, sulpiride and sultopride were 21.8-92.4, 31.7-156, 101-203, 16.4-56.2, 2.72-11.7, 13.6-84.0, 29.9-80.4, 70.1-1,120 and 35.7-2,990 ng/ml, respectively. A linear correlation between the daily dose and the plasma concentration was noted for sultopride, levomepromazine, sulpiride, haloperidol, chlorpromazine and zotepine.
We report here that in Escherichia coli, the anti-bacterial agent nalidixic acid induces transient stabilization and increased synthesis of sigma 32, accompanied by the induction of heat shock proteins (Dnak and GroEL proteins). The induction of heat shock proteins, increased synthesis of sigma 32, and stabilization of sigma 32 observed on treatment of wild-type cells with nalidixic acid were not observed in a nalA26 mutant, a strain that is resistant to nalidixic acid as the result of a mutation in the gyrA gene. Not only oxolinic acid, but also novobiocin, whose targets are the A and B subunits of DNA gyrase, respectively, also induced stabilization and increased synthesis of sigma 32. Thus, inhibition of the activity of DNA gyrase may cause stabilization and increased synthesis of sigma 32, resulting in turn in induction of heat shock proteins.
During development of the ascidian Halocynthia roretzi, the tadpole larva hatched from the tailbud embryo metamorphoses to the sessile adult with a body wall muscle. Although the adult body wall muscle is morphologically nonsarcomeric smooth muscle, it contains troponin complex consisting of three subunits (T, I, and C) as do vertebrate striated muscles. Different from vertebrate troponins, however, the smooth muscle troponin promotes actomyosin Mg2+-ATPase activity in the presence of high concentration of Ca2+, and this promoting property is attributable to troponin T. To address whether the embryonic/larval tail striated muscle and the adult smooth muscle utilize identical or different regulatory machinery, we cloned troponin T cDNAs from each cDNA library. The embryonic and the adult troponin Ts were encoded by distinct genes and shared only <60% identity with each other. Northern blotting and whole mount in situ hybridization revealed that these isoforms were specifically expressed in the embryonic/larval tail striated muscle and the adult smooth muscle, respectively. These results may imply that these isoforms regulate actin-myosin interaction in different manners. The adult troponin T under forced expression in mouse fibroblasts was unexpectedly located in the nuclei. However, a truncated protein with a deletion including a cluster of basic amino acids colocalized with tropomyosin on actin filaments. Thus, complex formation with troponin I and C immediately after the synthesis is likely to be essential for the protein to properly localize on the thin filaments.
We examined the influence of overexpression of LetD (CcdB) protein, an inhibitor of DNA gyrase encoded by the F factor of Escherichia coli, on DNA supercoiling and induction of heat shock proteins. Cells were transformed with a plasmid carrying the structural gene for LetD protein under control of the tac promoter, and LetD protein was induced by adding isopropyl beta-D-thiogalactopyranoside (IPTG) to the culture medium. Analysis by agarose gel electrophoresis in the presence of chloroquine revealed relaxation of plasmid DNA in cells depending on the concentration of IPTG employed for induction. Protein pulse-labeling experiments with [35S]methionine and cysteine revealed that synthesis of DnaK and GroEL proteins was also induced by IPTG, and concentrations necessary for DNA relaxation and induction of the heat shock proteins were much the same. Expression of mutant LetD protein lacking two amino acid residues at the C-terminus induced neither DNA relaxation nor the synthesis of DnaK and GroEL proteins. Induction of wild-type LetD protein but not mutant LetD protein markedly enhanced synthesis of sigma32. We interpret these results to mean that DNA relaxation in cells caused by the expression of LetD protein induces heat shock proteins via increased synthesis of sigma32.