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Biomedical subjects

H Nakajima

Publications and source records attributed to H Nakajima.

At least 55 records · Page 3Linked to original sources
PubMed2003

Costimulatory signals distinctively affect CD20- and B-cell-antigen-receptor-mediated apoptosis in Burkitt's lymphoma/leukemia cells.

CD20 is a B-cell differentiation antigen and known to induce apoptosis in Burkitt's lymphoma/leukemia (BL) cells upon antibody-mediated crosslinking. We examined the biological effect of CD20 crosslinking on BL cell lines and observed that apoptosis induction is accompanied by activation of multiple caspases, including caspase-8, -9, -3, -2, and -7. Further investigation revealed a clear synergism between apoptosis mediated by CD20 and by B-cell antigen receptor (BCR). Examination of the effect of simultaneous crosslinking of other cell surface molecules with crosslinking of CD20 or BCR on apoptosis induction showed that these molecules had either a synergistic or inhibitory effect on induction of apoptosis. It is worth noting that some molecules had a different effect on CD20- and BCR-mediated apoptosis. Simultaneous crosslinking of the molecules CD10, CD22, CD72, and CD80 inhibited BCR-mediated apoptosis, but enhanced CD20-mediated apoptosis. Further studies revealed that regulation of CD20-induced apoptosis by other costimulatory molecules is achieved by modification of caspase activation. CD20-mediated apoptosis in BL cells may provide not only a model for understanding the mechanism regulating clonal selection of B cells but a new therapeutic strategy for BL patients.

Annexin A5↗
PubMed2003

Nonmyeloablative stem cell transplantation with fludarabine and cyclophosphamide for patients with hematologic malignancies.

We conducted a multi-center phase I/II trial of nonmyeloablative stem cell transplantation for patients with hematologic malignancies. The aim of this trial was to assess the safety and feasibility of this treatment modality for older or younger patients with significant organ dysfunction, who could not be treated with conventional high dose chemoradiotherapy. Twelve patients were treated with a conditioning regimen consisting of fludarabine and cyclophosphamide, followed by peripheral blood stem cell transplantation from human leukocyte antigen (HLA) identical siblings. Nonhematologic toxicities were mild. Median time to absolute neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved in all patients, with or without donor leukocyte infusion. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%, respectively. Only one patient experienced early death within 100 days, caused by acute GVHD complicated by fungal infection. All patients except one achieved complete remission. With a median follow-up of 330 days, expected progression-free survival is 75%. Overall survival is 76%. Our study confirms that nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine conditioning is a safe and promising treatment for elderly patients with hematologic malignancies. A further study in large-scale setting is warranted.

Age Factors↗
PubMed2003

Effect of milrinone on vecuronium-induced neuromuscular block.

We examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 microg x kg-1x min-1 for 10 min, followed by an infusion at a rate of 0.5 microg x kg-1x min-1. Subjects in the control group received normal saline at a rate of 0.1 ml x kg-1 x h-1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg x kg-1 and fentanyl 2 microg x kg-1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg-1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train-of-four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train-of-four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train-of-four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train-of-four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.

Adult↗
PubMed2003

Cleavage line patterns in beagle dogs: as a guideline for use in dermatoplasty.

We prepared a map of the cleavage lines for beagle dogs, as a guideline for use of cleavage lines in dermatoplasty. The cleavage lines at the head resembled the orientation of the underlying muscles. Although the cleavage lines in the trunk were perpendicular to the body axis, those in the thoraco-abdominal region were parallel to the body axis. The cleavage lines at the limbs were parallel to the long axis of the limb on the cranial surface, but were perpendicular to the long axis of the limb on the lateral and caudal surfaces. Also, we recorded in detail the cleavage lines in the distal regions of the limbs.

Abdomen↗
PubMed2003

Identification of a novel variant in the phosphoenolpyruvate carboxykinase gene promoter in Japanese patients with type 2 diabetes.

Phospho enolpyruvate carboxykinase (PEPCK) plays an important role in gluconeogenesis and hepatic glucose production. To test the hypothesis that mutations of the PEPCK gene promoter contribute to the increased hepatic glucose production that leads to diabetes, we screened for polymorphisms of the PEPCK promoter region in 252 Japanese type 2 diabetic patients and 188 non-diabetic control subjects. A novel variant at position - 232 (C to G) was found at a similar frequency in type 2 diabetes patients (32 %) and control subjects (35 %) (p = 0.26). However, patients with the - 232 G/G genotype had an earlier age of onset than those with the - 232 C/C or - 232 C/G genotypes (p = 0.028). As the variant might well otherwise influence hormonal action, we transfected PEPCK-luciferase fusion gene constructs with the variant into human hepatoma cells and examined the response to dexamethasone, insulin, and cAMP. The reporter assay showed no significant difference in hormonal responses with the fusion gene containing the variant. Accordingly, the single-base variant at position - 232 of the PEPCK gene promoter is most probably not a major contributor to the pathogenesis of type 2 diabetes. However, this variation may be useful as a genetic marker for other metabolic disorders, especially in Japanese.

Aged↗
PubMed2003

Monitoring of neuromuscular block after administration of vecuronium in patients with diabetes mellitus.

BACKGROUND: We studied the supramaximal current for ulnar nerve stimulation during electromyographic monitoring of onset and recovery of neuromuscular block using a neuromuscular transmission module (M-NMT Module, Datex-Ohmeda) in patients with Type 2 diabetes undergoing anaesthesia with nitrous oxide, oxygen, isoflurane and fentanyl. METHODS: Thirty-six diabetic patients were randomly assigned to a post-tetanic count (PTC) group (n=17) or train-of-four (TOF) group (n=19). In addition, 30 non-diabetic patients were divided into control PTC (n=15) and TOF groups (n=15). RESULTS: In the diabetic patients (diabetes PTC and diabetes TOF groups), the mean supramaximal stimulating current was significantly higher than in the non-diabetic patients (control PTC and TOF groups) (50.5 (SD 14.1) vs 33.4 (6.1) mA, P<0.01). Onset of neuromuscular block (time to disappearance of T1) after vecuronium 0.1 mg kg(-1) in the diabetic patients did not differ significantly from that in the non-diabetic patients (276 (77) vs 244 (44) s, P=0.055). Time to return of PTC1 did not differ significantly between the diabetes and control PTC groups (21.0 (12.1) vs 15.7 (5.0) min, P=0.126). Times to return of T1 and T4 in the diabetes TOF group were significantly longer than in the control TOF group (T1: 37.5 (15.2) vs 25.7 (7.6) min, P=0.01; T4: 61.4 (23.7) vs 43.5 (11.4) min, P=0.01). During recovery, PTC and T4/T1 in the diabetes PTC and TOF groups were similar to those in the control PTC and TOF groups, respectively. T1/T0 in the diabetes TOF group was significantly less than in the control TOF group, 80-120 min after vecuronium (P<0.05). CONCLUSIONS: In diabetic patients, supramaximal current is higher than in non-diabetic patients. After vecuronium, onset of neuromuscular block and recovery of PTC or T4/T1 are not altered, but time to return of T1 or T4, and recovery of T1/T0 are delayed in diabetic patients.

Adult↗
PubMed2003

Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.

BACKGROUND: Autoimmune pancreatitis is a unique clinical entity proposed recently, and is sometimes associated with inflammation of other organs. AIMS: To examine the pathophysiology of the pancreas and other organs in patients with autoimmune pancreatitis. PATIENTS AND METHODS: We evaluated clinicopathological findings in six resected and one autopsied patient with autoimmune pancreatitis. The pancreas, peripancreatic tissue, bile duct, and gall bladder were examined histologically and immunohistochemically. Biopsied salivary gland and cervical lymph node of one patient were also examined. We also performed similar immunohistochemical examinations in pancreatectomy specimens from 10 patients with alcoholic chronic pancreatitis and biopsied salivary glands from five patients with Sjögren's syndrome. RESULTS: Stenosis of the extrahepatic bile duct was detected in all patients. Histological findings were characterised by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Immunohistochemically, diffusely infiltrating cells consisted predominantly of CD4 or CD8 positive T lymphocytes and IgG4 positive plasma cells. Similar inflammatory processes also involved the peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland. Lymph nodes were swollen with infiltration of IgG4 positive plasma cells. None of these findings was seen in alcoholic chronic pancreatitis or Sjögren's syndrome. CONCLUSIONS: The development of the specific inflammations in extensive organs as well as the pancreas in patients with autoimmune pancreatitis strongly suggests a close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.

Aged↗
PubMed2002

Effects of N-methyl-N'-nitro-N-nitrosoguanidine on the human colorectal polyps consecutively maintained in SCID mice.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatments for a long period induced morphological and molecular alterations in the benign human colorectal polyps which were maintained in the severe combined immunodeficient C.B17/N-scid/scid mice. Thirty four xenografts of colorectal polyps from five solitary polyp and three familial polyposis patients were examined for K-ras and p53 mutations. Six K-ras mutations were induced in 16 grafts treated with MNNG more than five times, while no K-ras mutations were detected in 14 untreated grafts (P<0.05). Additional and new K-ras mutations were also induced in two polyps in which K-ras mutation had pre-existed. p53 mutations were not observed in both MNNG-treated and untreated groups. The mutations in K-ras gene were induced at codon 12 (GGT-->GAT) except one at codon 13 (GGC-->GGT). The results indicate that K-ras mutation plays an important role in human colorectal carcinogenesis as is the case in experimental animals.

Animals↗
PubMed2002

Video-assisted total glandectomy and immediate reconstruction for breast cancer.

This paper describes a new surgical technique and our clinical experience with video-assisted endoscopic total glandectomy via a middle axillary incision followed by immediate reconstruction with latissimus dorsi muscle flap (LDMF) performed in 17 patients with bigger, multiple tumors or extensive ductal spread of breast cancer. The novel techniques in this procedure are as follows: (1) By securing patients in a semi-lateral position and suspending the upper extremity, either supine or semi-lateral position can be easily achieved by simply rotating the operating table, resulting in a wider working space from the axillary to hip area. (2) By applying a retractor for skin flap traction, endoscopic glandectomy and reconstruction become safe and reliable. As a result, the mean number and size of tumors were 1.2 and 4.12 cm, respectively. Surgical margins of all the cases were pathologically negative and there were no recurrences observed during 14 months follow-up to date. Esthetic results have been satisfactory and the surgical wounds were not visible from the front in any case. Compared to mastectomy, this procedure shows the same therapeutic results, but offers a greater esthetic and psychological advantage to all the patients.

Breast Neoplasms↗
PubMed2002

Laparoscopic features of primary biliary cirrhosis in AMA-positive and AMA-negative patients.

BACKGROUND AND STUDY AIMS: Antimitochondrial antibody (AMA)-negative primary biliary cirrhosis (PBC) has been difficult to diagnose. Laparoscopic features of AMA-negative PBC were evaluated in comparison with those of AMA-positive PBC and autoimmune hepatitis. PATIENTS AND METHODS: 71 patients who fulfilled the diagnostic criteria for PBC were enrolled in the study; 48 were AMA-positive and 23 were AMA-negative. As a disease control, 46 autoimmune hepatitis patients were included. Both the frequency and specificity of each laparoscopic finding were evaluated. A laparoscopic scoring system was introduced, which used, common and uncommon laparoscopic findings, and was evaluated for the diagnosis of AMA-negative PBC. RESULTS: The characteristic laparoscopic findings for AMA-positive PBC were yellowish-white marking (92 %), dark-brown discoloration (73 %), gentle undulation (67 %), reddish patch (38 %), and yellowish-white nodules (32 %). On the other hand, laparoscopic findings such as trench-like depression, reddish markings, and wide and small depressions were uncommon in PBC compared with autoimmune hepatitis. The frequencies of characteristic and uncommon laparoscopic findings did not differ statistically between AMA-positive and AMA-negative PBC, but were different between AMA-positive or AMA-negative PBC and autoimmune hepatitis. Scores based on common and uncommon laparoscopic findings were 5.5 +/- 1.5 (mean +/- SD) in AMA-positive PBC, 5.6 +/- 2.0 in AMA-negative PBC, and - 0.30 +/- 0.5 in autoimmune hepatitis. CONCLUSION: The laparoscopic findings in AMA-negative PBC did not differ from those of AMA-positive PBC. A laparoscopic scoring system may be helpful in the diagnosis of AMA-negative PBC.

Adult↗
PubMed2002

Studies on the metabolic fate of M17055, a novel diuretic (6). Assessment for drug-drug interactions of M17055 in metabolism, distribution and excretion.

1. The potential of M17055, a novel diuretic candidate, to affect the activities of human CYP enzymes, alter the plasma unbound fraction and compete with concomitant drugs in renal secretion as part of an assessment for drug-drug interactions in metabolism, distribution and excretion was investigated. 2. The effects of M17055 on the activities of human CYP1A2, CYP2E1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were considered negligible at clinically relevant concentrations. 3. The majority of M17055 (99%) was bound to human plasma proteins, but it is unlikely to alter the binding of other clinically relevant drugs. 4. The renal clearance of M17055 (corrected for the plasma unbound fraction in male rats) substantially exceeded the glomerular filtration rate and was markedly reduced by treatment with probenecid, suggesting that the renal excretion of M17055 is controlled predominantly by an active secretion mechanism. 5. The results show that M17055 is unlikely to cause or undergo significant pharmacokinetic interactions with concomitant drugs in metabolism and distribution. However, when it is administered simultaneously with certain organic anions, drug-drug interactions during kidney excretion may be possible.

Animals↗
PubMed2002

[A case of ischemic dilated cardiomyopathy, mitral regurgitation and congestive heart failure successfully treated by Batista operation, coronary artery bypass grafting and mitral valve replacement; usefulness of myocardial scintigraphy].

A 75-year-old man diagnosed as having ischemic dilated cardiomyopathy, congestive heart failure and mitral regurgitation underwent left ventricle volume reduction operation (Batista), coronary bypass grafting and mitral valve replacement because myocardial infarction had developed at lateral, inferior and small area of apex wall, not at interventricular septum. Left ventricular endodiastolic volume index and left ventricular endosystolic volume index decreased from pre-operative values of 155, and 128 ml/m2 to post-operative values of 113, and 82 ml/m2, respectively. Left ventricular ejection fraction increased from a pre-operative value of 17% to a post-operative value of 27%. This evaluation was performed by myocardial scintigraphy (quantitative gated spect: QGS). This method was bloodless and useful for determination of indication of left ventricle volume reduction surgery including Batista operation and pre- and post-operative evaluation of this type of surgery. Today, Batista operation is, generally speaking, performed for non-ischemic dilated cardiomyopathy. In this case, however, Batista operation was applied to ischemic dilated cardiomyopathy and was very effective.

Aged↗
PubMed2002

Phosphate removal and recovery by a novel electrolytic process.

The possibility of removing and recovering phosphate from wastewater by a novel electrolytic process was investigated experimentally. In the process, ion electrodes are immersed in synthetic wastewater and direct current (DC) is applied to coagulate phosphate on the surface of the anode. Experimental results demonstrated that at electric current densities ranged from 0.001 to 0.1 mA/cm2, phosphate was removed and recovered as phosphate-rich aggregates formed on the anode surface. Decreases in phosphate concentration at bulk liquid were in fairly good agreement with the amounts of phosphate in the aggregates. Moreover, the removal rate of phosphate was increased with increasing electric current. In addition, as heavy metal anions such as Cu2+ deposit on the counter electrode (cathode), it was thought that relatively pure phosphate could be obtained by the present process.

Conservation of Natural Resources↗
PubMed2001

Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: implications in negative regulation of STAT5-dependent transcription.

Signal transducers and activators of transcription (STATs) play a central role in cytokine signaling. Activating and repressing gene transcription is a dynamic process involving chromatin remodeling by histone acetylases and deacetylases, yet the role of this process in STAT-dependent transcription remains largely unknown. In a search for STAT5-interacting proteins by yeast two-hybrid screening, we identified the nuclear receptor co-repressor SMRT (silencing mediator for retinoic acid receptor and thyroid hormone receptor) as a potential STAT5-binding partner. SMRT binds to both STAT5A and 5B, and strongly repressed STAT5-dependent transcription in vitro. SMRT binds to the N-terminal coiled-coil domain of STAT5 and a mutation within this region previously found to render STAT5 hyperactive in response to cytokines abolished the interaction with SMRT. Overexpression of SMRT suppressed the induction of STAT5 target genes by interleukin-3, whereas the histone deacetylase inhibitor trichostatin A effectively enhanced and prolonged their expression. Together, these findings illuminate the potential role of SMRT in down-regulating STAT5 activity, with a consequent reduction of STAT5 target gene expression.

Blotting, Northern↗
PubMed2001

Essential role of Stat5 for IL-5-dependent IgH switch recombination in mouse B cells.

IL-5 stimulation of CD38-activated murine splenic B cells induces mu-gamma1 CSR at the DNA level leading to a high level of IgG1 production. Further addition of IL-4 in the system enhances IL-5-dependent mu-gamma1 CSR. Although some of the postreceptor signaling events initiated by IL-5 in activated B cells have been characterized, the involvement of Stat in IL-5 signaling has not been thoroughly evaluated. In this study, we examined the activation of Stat5 and activation-induced cytidine deaminase (AID) in CD38-activated murine splenic B cells by IL-5. The role of Stat5a and Stat5b in IL-5-induced mu-gamma1 CSR and also IgG1 and IgM production was documented, as IL-5 does not act on CD38-stimulated splenic B cells from Stat5a(-/-) and Stat5b(-/-) mice. Expression levels of CD38-induced germline gamma1 transcripts and AID in Stat5a(-/-) and Stat5b(-/-) B cells upon IL-5 stimulation were comparable to those of wild-type B cells. The impaired mu-gamma1 CSR by Stat5b(-/-) B cells, but not by Stat5a(-/-) B cells, was rescued in part by IL-4, as the addition of IL-4 to the culture of CD38- and IL-5-stimulated B cells induced mu-gamma1 CSR leading to IgG1 production. Analysis of cell division cycle number of wild-type B cells revealed that mu-gamma1 CSR was observed after five or six cell divisions. Stat5a(-/-) and Stat5b(-/-) B cells showed similar cell division cycles, but they did not undergo mu-gamma1 CSR. Our data support the notion that both Stat5a and Stat5b are essential for IL-5-dependent mu;-gamma1 CSR and Ig secretion; however, their major target may not be AID. Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

ADP-ribosyl Cyclase↗
PubMed2001

Conformational dynamics of the transcriptional regulator CooA protein studied by subpicosecond mid-infrared vibrational spectroscopy.

CooA, which is a transcriptional regulator heme protein allosterically triggered by CO, is studied by femtosecond visible-pump mid-IR-probe spectroscopy. Transient bleaching upon excitation of the heme in the Soret band is detected at approximately 1979 cm(-1), which is the absorption region of the CO bound to the heme. The bleach signal shows a nonexponential decay with time constants of 56 and 290 ps, caused by the rebinding of the CO to the heme. About 98% of dissociated CO recombines geminately. The geminate recombination rate in CooA is significantly faster than those in myoglobin and hemoglobin. The angle of the bound CO with respect to the porphyrin plane is calculated to be about 78 degrees on the basis of the anisotropy measurements. A shift of the bleached mid-IR spectrum of the bound CO is detected and has a characteristic time of 160 ps. It is suggested that the spectral shift is caused by a difference in the frequency of the bound CO in different protein conformations, particularly in an active conformation and in an intermediate one, which is on the way toward an inactive conformation. Thus, the biologically relevant conformation change in CooA was traced. Possible assignment of the observed conformation change is discussed.

Bacterial Proteins↗
PubMed2001

Cloning and sequence analysis of cnaA gene encoding the catalytic subunit of calcineurin from Aspergillus oryzae.

Calcineurin has been implicated in ion-homeostasis, stress adaptation in yeast and for hyphal growth in filamentous fungi. Genomic DNA and cDNA encoding the catalytic subunit of calcineurin (cnaA) were isolated from Aspergillus oryzae. The cnaA open reading frame extended to 1727 bp and encoded a putative protein of 514 amino acids. Comparative analysis of the nucleotide sequence of cnaA genomic DNA and cDNA confirmed the presence of three introns and a highly conserved calmodulin binding domain. The deduced amino acid sequence was homologous to calcineurin A from Aspergillus nidulans (92%), Neurospora crassa (84%), human (67%), Saccharomyces cerevisiae (58%) and Schizosaccharomyces pombe (54%). Further, A. oryzae cnaA cDNA complemented S. cerevisiae calcineurin disruptant strain (Deltacmp1 Deltacmp2), which was not viable in the presence of high concentrations of NaCl (1.2 M) and at alkaline pH 8.5.

Amino Acid Sequence↗