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Biomedical subjects

C Nakamura

Publications and source records attributed to C Nakamura.

At least 73 records · Page 4Linked to original sources

[A case of endotracheal tube obstruction caused by pneumoperitoneum during laparoscopic cholecystectomy].

A 56-year-old man with cholecystolithiasis was scheduled for laparoscopic cholecystectomy. Anesthesia was induced with pentazocine and propofol i.v., and the trachea was intubated using vecuronium i.v. Anesthesia was maintained with 70% nitrous oxide and 1-3% sevoflurane in oxygen, and vecuronium was used for muscle relaxation. The lungs were mechanically ventilated with a tidal volume of 600 ml and a respiratory rate of 8 cycles.min-1. Following induction of carbon dioxide pneumoperitoneum, blood pressure, PETCO2 and peak inspiratory pressure gradually increased. PETCO2 increased from 33 mmHg to 48 mmHg despite increase in the respiratory rate to 20 cycles.min-1. By 45 minutes after the beginning of surgery, PETCO2 had increased to 60 mmHg, and ventilation of the lungs was impossible. Bronchofiberscopy revealed obstruction of the endotracheal tube by tracheal mucosa. The endotracheal tube was then drawn out by 2 cm with slight recovery of ventilation. After 1 h 16 min of surgery, it was observed that the patient had developed pneumoscrotum and subcutaneous emphysema extending from femoral area, abdomen, and thorax to the right neck. Chest rentogenography revealed a slight tracheal shift and subcutaneous emphysema. One hour after the end of surgery, PaCO2 was 48.9 mmHg under spontaneous respiration. We speculate that the pneumoperitoneum shifted the tracheal carina cephalad, causing obstruction of the endotracheal tube. Our findings show that displacement of the endotracheal tube must be carefully monitored during laparoscopic cholecystectomy.

Anesthesia, Inhalation↗

Effect of dicetylphosphate or stearic acid on spontaneous transfer of protein from influenza virus-infected cells to dimyristoylphosphatidylcholine liposomes.

Membrane proteins, such as viral spike, were transferred spontaneously from influenza virus-infected cells to various liposomes. The protein transfer was enhanced by the presence of negative charged component dicetylphosphate (DCP) or stearic acid (SA) in dimyristoylphosphatidylcholine (DMPC) liposomes. The lowering of membrane fluidity did not relate to the effect of DCP or SA on protein transfer in this study. We considered that the alteration of membrane properties, such as construction of the surface or stability of transferred protein in liposomes, due to the specific structure of DCP or SA is responsible for the enhancement of spontaneous protein transfer by the presence of the amphiphilic components.

Animals↗

Pyruvate alleviates toxic effects of ethanol on cells in culture.

Cytotoxic effects of ethanol on cultured human hepatocytes and fibroblasts differed with the type of culture medium used. When cytotoxic effects of ethanol were compared between culture systems using either RPMI-1640 or Dulbecco's modified Eagle's medium (DMEM), the cytotoxicity was more prominent with the former medium than with the latter. A reduction of the cytotoxic effects appeared to be due to the pyruvate contained in DMEM. The protective effect of pyruvate against ethanol toxicity may be related to tricarboxylic acid (TCA) cycle activity because addition of malate to the medium also reduced the cytotoxic effects. Our results suggest that drug cytotoxicity testing in vitro must be done using various types of culture medium.

Cell Division↗

Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects.

OBJECTIVE: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. METHODS: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. RESULTS: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Oral formulations of adefovir dipivoxil: in vitro dissolution and in vivo bioavailability in dogs.

The effect of formulation on oral bioavailability of the antiviral nucleotide analogue adefovir from the prodrug adefovir dipivoxil was examined in beagle dogs. A suspension formulation of adefovir dipivoxil granules was administered to five fasted male beagle dogs (250 mg prodrug per dog; 135.7 mg-equiv of adefovir per dog). Tablets prepared from the same granulation (batch B94) were administered at 2 x 125 mg prodrug per dog. In addition, the same tablets were administered to dogs in the fed state or following pentagastrin pretreatment. Two further tablet batches (H94 and D501) with slight formulation changes were also evaluated in pentagastrin pretreated dogs (n = 5). Concentrations of adefovir in plasma were determined by HPLC following fluorescence derivatization. Tablet dissolution was examined at pH 2.0. One batch of adefovir dipivoxil tablets showed a 5-fold slower dissolution rate in vitro (B94 = H94 >> D501). Adefovir dipivoxil was completely converted to adefovir following oral absorption in dogs. The oral bioavailability of adefovir from the suspension was 35.0 +/- 8.9%. The oral bioavailability of adefovir from the tablet formulation was 34.7 +/- 10.3%, 37.2 +/- 4.5%, and 44.9 +/- 5.9% in fasted dogs, fed dogs and fasted dogs pretreated with pentagastrin, respectively. All three tablet batches had equivalent bioavailability in dogs. Oral bioavailability of adefovir from the prodrug in dogs (35-46%) was unaffected by formulation, food, or the acidic pH of the gastrointestinal tract. In vitro dissolution of adefovir dipivoxil tablets did not correlate with oral bioavailability. Oral bioavailability of adefovir dipivoxil appears to be limited by low permeability and biological conversion of the prodrug to adefovir.

Adenine↗

Variation in coxII intron in the wild ancestral species of wheat.

To study the maternal lineage and evolution of polyploid species of wheat, variation in mitochondrial DNA was investigated in Triticum and Aegilops by PCR-aided RFLP analysis. A 1.3 kb region containing the intron of coxII was studied using 20 accessions from five species of Sitopsis section of Aegilops, one species of Einkorn wheat, four species of tetraploid wheat, and one species of common wheat. Only three restriction site changes and a single deletion/insertion were found among 884 restriction fragments surveyed. This fact suggests the highly conserved nature of this region within Triticum and Aegilops. Four haplo-types were recognized in coxII intron. A parsimonious relationship indicated that three haplo-types were independently derived from one prototype which was found in wild Einkorn and Aegilops species except for Ae. speltoides. All but one accession of Ae. speltoides possessed a derivative haplo-type, common in Timopheevi wheat. The result supported the hypothesis that Ae. speltoides donated the G genome to Timopheevi wheat; however did not agree with that Ae. speltoides was the B genome donor to the Emmer and common wheat.

Biological Evolution↗

[The basics for establishing a needlestick injury prevention program in hospitals].

Although the risk of occupationally acquired infection is a matter of considerable concern for health care workers, the problem of needlestick injuries has yet to be fully understood in Japan. We investigated 257 cases of needlestick injuries in five Nagoya Municipal Hospitals from 1989 to 1994 using the Japan EPInet. The number of needlestick injuries increased each year of the study. In one of these hospitals, the Higashi Municipal Hospital, a specialist committee began activities in April, 1993, and protective equipment and devices were also introduced during 1994. HCV contamination injuries accounted for 70%-80% of the total number of injuries reported during the 1991-1994 period at the four hospitals and during 1991-1992 period at the Higashi Municipal Hospital. At the Higashi Municipal Hospital, HCV contamination injuries decreased from 22 cases (48%) in 1993, to 15 cases (25%) in 1994. The use of the Japanese EPINet for analytical purposes enabled us to clearly identify the causes and status of needlestick injuries, resulting in the establishment of an effective prevention program.

Female↗

Effects of betamipron on cisplatin nephrotoxicity and its pharmacokinetics in rats.

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) on the nephrotoxicity of cisplatin were examined as indicated by body weight gain, ratio of kidney weight to body weight, blood urea nitrogen and serum creatinine levels in tumor-bearing rats. The results showed clearly that administration of BP 1 h after cisplatin treatment affords protection against the nephrotoxicity of cisplatin. Furthermore, the addition of BP to cisplatin had no apparent effect on the efficacy of cisplatin against Walker 256 carcinosarcoma cells in rats. In addition, no observed significant difference in plasma cisplatin concentration between cisplatin with alkaline solution and cisplatin with BP may be partly attributed to the decrease in the cisplatin exsorption to the intestine and its excretion to bile, and to an increase in cisplatin excretion to the urine.

Alanine↗

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis with membranous nephropathy in remission.

A 47-year-old woman developed pulmonary hemorrhage and an increase in proteinuria during remission of membranous nephropathy. Renal biopsy revealed crescentic glomerulonephritis. She also had a high perinuclear antineutrophil cytoplasmic antibody level, so a diagnosis of myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis was made. After immunosuppressive therapy was started, the pulmonary hemorrhage resolved and her proteinuria decreased. Renal biopsy was repeated after treatment and showed histological improvement. This case suggests that there may be a relationship between membranous nephropathy and myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis.

Anti-Glomerular Basement Membrane Disease↗

Betamipron reduces cisplatin nephrotoxicity in rodents without modifying its antileukemic activity in mice.

Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the damage observed in the kidney is localized to the proximal tubule cells, we investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cisplatin treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity, increase and subsequent decrease in gamma-glutamyl transferase activities, and increase in beta 2-microglobulin level observed after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.

Acetylglucosaminidase↗

Dharmendra antigen but not integral M. leprae is an efficient inducer of immunostimulant cytokine production by human monocytes, and M. leprae lipids inhibit the cytokine production.

Killed integral Mycobacterium leprae, Mitsuda antigen, and chloroform-treated M. leprae, Dharmendra antigen (Dh-Ag), have been used for the classification of leprosy patients based on cell-mediated immunity. Heat-killed M. leprae also were used as a component of the Convit vaccine. Human blood monocytes were stimulated with M. leprae or Dh-Ag and their cytokine-inducing ability was compared. Monocytes were cultured in the presence of fresh human serum because of the efficiency of cytokine induction and the phagocytosis of M. leprae have been shown to be optimal in the presence of fresh serum. M. leprae and Dh-Ag were equally phagocytosed by monocytes. Dh-Ag was more potent than M. leprae in the induction of immunostimulatory/proinflammatory cytokines, interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF). In contrast, a comparable level of IL-1ra, an immunosuppressive cytokine, was induced by M. leprae and Dh-Ag. The lipids extracted from M. leprae induced none of these cytokines by monocytes. Nevertheless, when monocytes were pretreated with the lipids followed by stimulation with Dh-Ag, productions of IL-1, IL-6 and TNF were all inhibited in a dose-dependent manner. However, the lipids did not inhibit the cytokine production induced by other stimuli including BCG and lipopolysaccharide. Moreover the lipids did not affect the production of IL-1ra. These results suggest that the lipids from M. leprae are responsible for the poor cytokine-inducing ability of M. leprae, thus favoring their infection. These results also suggest that Dh-Ag rather than integral M. leprae may be useful as a vaccine candidate because Dh-Ag is able to induce a large amount of cytokines from monocytes.

Antigens, Bacterial↗

[A case of saphenous vein graft donor site dermatitis].

A 65-year-old male, underwent coronary artery bypass grafting, was seen for a saphenous vein graft donor site dermatitis, at 3 weeks after the surgery. He complained pruritic erythema on the lesion identical to those with numbness. The lesion was controlled with topical steroid for 10 days. Saphenous vein graft donor site dermatitis has not been recognized well by surgeon in Japan and the etiology is still unclear.

Aged↗

Myeloperoxidase antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in a very elderly patient with generalized vasculitis at autopsy.

An 86-year-old woman was admitted with hemoptysis and rapid deterioration of renal function. Renal biopsy disclosed necrotizing crescentic glomerulonephritis. Based on positivity for serum myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA), MPO-ANCA-associated glomerulonephritis was diagnosed. Steroid pulse therapy was performed, but the patient died after the second course. Autopsy revealed renal vasculitis with fibrinoid necrosis extending to the level of the arcuate arteries. Vasculitis was also observed in the liver, adrenal gland, uterus, and spleen, suggesting the presence of microscopic polyarteritis. This case demonstrates the broad spectrum of MPO-ANCA-positive vasculitis and suggests the need for a more effective therapy suitable for very elderly patients.

Aged↗

[Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position].

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Björk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Björk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Björk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Björk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.

Aged↗

Intra-articular calcifying synovial sarcoma mimicking synovial chondromatosis.

A case of intra-articular calcifying synovial sarcoma of the right knee joint in a 27-year-old man is reported. Prior to admission the patient had been suffering pain in the right knee for 5 years. Plain radiographs showed multiple calcified densities in the anterior aspect of the right knee closely mimicking synovial chondromatosis. Histological examination revealed that the lesion was a synovial sarcoma with extensive calcification subjacent to the synovial surface. Although intra-articular calcifying synovial sarcoma is very rare, it is important to be aware of the fact that synovial sarcoma, as well as synovial chondromatosis, can be present as a calcified lesion in the joint cavity.

Adult↗

Determination of R(+)- and S(-)-lansoprazole using chiral stationary-phase liquid chromatography and their enantioselective pharmacokinetics in humans.

PURPOSE: Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects. METHODS: Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-phenylcarbamate)), OF (cellulose tris(4-chlorophenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamate)) were investigated. RESULTS: Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean Cmax and the AUC values of R(+)-enantiomer were 3-5 times greater than those of S(-)-enantiomer following oral administration of 30 mg of racemic lansoprazole. The CLtot values of R(+)-enantiomer were significantly smaller than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human serum proteins was significantly greater than that of S(-)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(-)-enantiomer was significantly greater than that of R(+)-enantiomer. CONCLUSIONS: The stereoselective pharmacokinetics of lansoprazole enantiomers is likely due to its stereoselective protein binding and/or metabolism.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Protective effects of N-benzoyl amino acids on cisplatin nephrotoxicity in rats.

The protective effects of N-benzoyl amino acids (NAAs) and piperacillin (PIP), anionic transport inhibitors, against the nephrotoxicity of cisplatin were examined in rats. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with i.p. NAAs or PIP. Rats were sacrificed on day 5 after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Treatments with NAAs were an effective means of protection against cisplatin-induced nephrotoxicity. The combination of cisplatin with NAAs containing a short and straight chain significantly suppressed (p < 0.05) the changes in body, kidney and liver weights, BUN and serum Cr. Further, betamipron (BP) at a 2000 mg/kg dose showed no apparent effect on the body, kidney and liver weights, BUN and serum Cr levels in rats. The combination of cisplatin with PIP caused a loss in body weight. The protective effects of PIP against cisplatin toxicity are inferior to those of BP when compared at 250 mg/kg doses.

Alanine↗