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Biomedical subjects

J Nishikawa

Publications and source records attributed to J Nishikawa.

At least 19 recordsLinked to original sources
PubMed1995

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells.

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.

Acute Disease↗
PubMed1995

Vitamin D receptor contains multiple dimerization interfaces that are functionally different.

The vitamin D receptor mediates the signal of 1 alpha, 25-dihydroxyvitamin D3 by binding to vitamin D responsive elements in DNA as a homodimer or as a heterodimer composed of one vitamin D receptor subunit and one retinoid X receptor subunit. We have mapped the dimerization interfaces of the vitamin D receptor that is involved in homo- or heterodimer formation in the absence of DNA. While deletion of the first zinc finger region of vitamin D receptor diminished homodimerization activity, it did not affect heterodimerization. In contrast, a deletion just beyond the zinc finger region affected heterodimerization with retinoid X receptor, but not homodimerization. The zinc finger region alone could form a homodimer with full-length vitamin D receptor, but not a heterodimer with retinoid X receptor. The carboxy-terminal region was also necessary for heterodimer formation. This region showed only a weak dimerization activity in the absence of ligand, but this was dramatically increased in the presence of ligand for both homo- and heterodimerization. These results suggest that the vitamin D receptor has at least three dimerization interfaces whose functions are apparently distinguishable. These are located in the first zinc finger region, the region just beyond this zinc finger and in the carboxy-terminal region.

Amino Acid Sequence↗
PubMed1995

Rabphilin-3A binds to a M(r) 115,000 polypeptide in a phosphatidylserine- and Ca(2+)-dependent manner.

Rabphilin-3A is a putative target protein for Rab3A/Smg 25A, which is a member of the Ras-related small GTP-binding protein and implicated in neurotransmitter release from the synapse. Rabphilin-3A is composed of two functionally different domains: the N-terminal Rab3A-binding and the C-terminal phosphatidylserine- and Ca(2+)-binding domains. The C-terminal domain has two copies of an internal repeat that are homologous to the C2 domains of protein kinase C, synaptotagmin, and phospholipase A2 and C-gamma 1, which are known to bind phosphatidylserine and Ca2+. In this study, we attempted to identify the Rabphilin-3A-interacting molecule in bovine brain by use of an overlay assay technique. The 32P-labeled C-terminal fragment of Rabphilin-3A (281-704 amino acids) bound to a protein molecule with a M(r) of about 115 kDa which was immobilized on a nitrocellulose sheet. This protein was highly purified and characterized. The binding of the 32P-labeled C-terminal fragment to this protein was dependent on both phosphatidylserine and Ca2+, and inhibited by an excess amount of the C-terminal fragment and the C2 domain fragment (396-704 amino acids) but not by the N-terminal fragment (1-280 amino acids). These results indicate that Rabphilin-3A binds to a protein molecule with a M(r) of 115 kDa through the C2 domain in the presence of phosphatidylserine and Ca2+.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Myocardial glucose metabolism in noninsulin-dependent diabetes mellitus patients evaluated by FDG-PET.

UNLABELLED: Diabetes mellitus (DM) is one of several factors influencing the assessment of myocardial viability using fluorine-18 fluorodeoxyglucose (FDG) PET. METHODS: To compare the myocardial glucose metabolism of normal subjects to patients with DM, we performed a quantitative FDG study during insulin clamp, oral glucose loading and fasting in nine normal volunteers and eight patients with noninsulin-dependent DM (NIDDM). RESULTS: During oral glucose loading, myocardium-to-background (MB) ratio remarkably deteriorated in NIDDM patients compared with normals because of high plasma glucose and low serum insulin. Myocardial glucose utilization (MGU) rates in NIDDM patients were also lower than those in normal volunteers. MB ratio of FDG remarkably improved with insulin clamp in NIDDM patients compared with oral glucose loading. MGU rates during insulin clamp were still slightly lower than in the normal volunteers despite low plasma glucose and adequate plasma insulin. CONCLUSION: The insulin clamp method may be very useful in NIDDM patients for improved myocardial FDG uptake compared to oral glucose loading or fasting, but slight decreases in MGU rates during insulin clamp in NIDDM patients may be because of insulin resistance (GluT4 abnormality).

Adult↗
PubMed1994

Difference and similarity of DNA sequence recognized by VDR homodimer and VDR/RXR heterodimer.

Nuclear receptors for the thyroid hormone and vitamin A and D cooperate with the retinoid X receptor (RXR) in activating the transcription. Although the hormone response elements for these receptors have been proposed in which spacing of the direct repeated motifs determine the specificity (so called 3-4-5 rule), vitamin D response elements (VDREs) in the natural context consist of often imperfect direct repeats. Vitamin D receptor (VDR) alone can bind to the mouse osteopontin (mSPP-1) VDRE, which contains a direct repeat separated by 3 nucleotides, but not to the rat osteocalcin (rOST) VDRE having inexact direct repeat. The presence of RXR not only allows the VDR to bind to the rOST VDRE, but also increases the binding affinity for the mSPP-1 VDRE. The RXR/VDR heterodimer exhibits the similar affinity constants for the mSPP-1 VDRE and the rOST VDRE, in spite of the apparently different affinities for two VDREs of the VDR homodimer. A random oligonucleotide selection procedure revealed that the consensus sequence selected by the RXR homodimer is the direct repeat spaced by one A residue. In contrast, the sequences preferentially selected by the VDR homodimer and the VDR/RXR heterodimer are similar, which are the direct repeats spaced by 3 nucleotides. The difference and similarity of DNA sequence recognition are discussed.

Animals↗
PubMed1994

Characterization of phe B gene encoding catechol 2,3-dioxygenase.

DNA sequence of the phe B gene isolated from a chromosome of the phenol degrading bacterium Pseudomonas putida BH is identical to that of the dmp B gene from the phenol degradative plasmid, pVI150. Catechol 2,3-dioxygenase encoded by phe B showed similar substrate specificity to that of xyl E. However, Phe B has much smaller Km values than Xyl E, indicating that Phe B is useful for treatment of low concentrations of catechol derivatives in waste water.

Biodegradation, Environmental↗
PubMed1993

Two functionally different domains of rabphilin-3A, Rab3A p25/smg p25A-binding and phospholipid- and Ca(2+)-binding domains.

Rabphilin-3A is a putative target molecule for rab3A p25/smg p25A, which is a member of a ras p21-related small GTP-binding protein and implicated in neurotransmitter release from the synapse. Rabphilin-3A has two copies of an internal repeat that are homologous to the C2 domains of protein kinase C, synaptotagmin, and phospholipase A2, which are known to bind to phospholipid in a Ca(2+)-dependent manner. In the current study, we have investigated the functional domains or rabphilin-3A by use of three recombinant proteins as follows: full rabphilin-3A (1-704 amino acids), an N-terminal fragment (1-280 amino acids), and a C-terminal fragment containing the C2 domains (281-704 amino acids). Both rabphilin-3A and the C-terminal fragment bound to phospholipid in the presence of Ca2+, but the N-terminal fragment did not bind to phospholipid. 45Ca2+ bound to rabphilin-3A and the C-terminal fragment only in the presence of phospholipid but did not bind to the N-terminal fragment. The GTP gamma S-bound form of rab3A p25 bound to both rabphilin-3A and the N-terminal fragment but did not bind to the C-terminal fragment. These results indicate that rabphilin-3A has at least two functionally different domains, the N-terminal rab3A p25-binding and C-terminal phospholipid- and Ca(2+)-binding domains.

Adaptor Proteins, Signal Transducing↗
PubMed1993

A measurement process for evaluating clinical teachers in internal medicine.

With input from faculty members and residents in the internal medicine residency training program at McMaster University, Hamilton, Ont., the authors developed a form to evaluate attending physicians in clinical teaching units according to 14 domains of performance. Although brief, the form included all main areas of teacher performance, allowed specification of attending physician behaviour and differentiated areas of strengths and weaknesses between and within attending physicians. The authors describe the new evaluation process and the results for 41 attending physicians.

Canada↗
PubMed1993

Vitamin D receptor zinc finger region binds to a direct repeat as a dimer and discriminates the spacing number between each half-site.

1 alpha,25-Dihydroxyvitamin D3, the most active metabolite of vitamin D3, is a multifunctional agent. The actions of 1 alpha,25-dihydroxyvitamin D3 are mediated through its receptor that activates the specific genes in a ligand-dependent manner. In order to investigate the details of DNA binding properties of vitamin D receptor, we have developed the overexpression and purification system of vitamin D receptor DNA binding domain. The purified peptide could specifically bind to the osteopontin-derived vitamin D responsible element (VDRE) but not to the osteocalcin and the calbindin D-9k-derived VDREs, as determined by bandshift analysis. The osteopontin VDRE contains a direct repeat of GGTTCA motif separated by 3 nucleotides, whereas the osteocalcin and calbindin D-9k VDREs have inadequate direct repeat. Further analyses using synthetic oligonucleotides revealed that vitamin D receptor DNA binding domain could discriminate the spacing number between the consensus steroid-responsible element motif and had different affinities to direct repeats that consisted of various related sequences. These studies give insight into ways in which vitamin D receptor mediates the signal of 1 alpha,25-dihydroxyvitamin D3.

Animals↗
PubMed1993

Relationship between distribution of hypertrophy and electrocardiographic changes in hypertrophic cardiomyopathy.

To assess the relationship between the distribution of hypertrophy and electrocardiographic changes in patients with hypertrophic cardiomyopathy, magnetic resonance imaging and ECG findings were correlated in 25 patients with apical hypertrophy (group I), 15 patients with both apical and basal hypertrophy (group II), and 11 patients with hypertrophy localized to the basal left ventricle (group III). The number of precordial leads with negative T waves (-0.5 mV or more) was greater in group I than in groups II and III (I = 3.0 +/- 1.5, II = 1.7 +/- 1.5, III = 0.3 +/- 0.6; p < 0.01). Giant negative T waves (-1.0 mV or more) in precordial leads were found in 13 patients (52%) in group I and five patients (33%) in group II but were not found in group III. In contrast, tall positive T waves (> or = 1.0 mV) in precordial leads were found in two patients (13%) in group II and five (45%) in group III but were not found in group I. These results suggest that the distribution of hypertrophy in patients with hypertrophic cardiomyopathy produces a particular T wave polarity in precordial leads.

Adult↗
PubMed1993

A proposal for enhancing the quality of clinical teaching: results of a department of medicine's educational retreat.

New challenges for clinical teachers include incorporating a deeper appreciation of the use of the published literature in day-to-day practice and teaching, responding to the profusion of diagnostic tests and treatments, and dealing with changing practical difficulties. We report a summary of a retreat conducted by our Department of Medicine in which our faculty presented and refined strategies they had developed to deal with these challenges. Areas of discussion include developing an effective medical team managing time on a busy clinical service, teaching pathophysiology, teaching clinical skills, and teaching critical appraisal. Our observations are likely to be useful to clinicians involved in patient-centred teaching in wards and clinics, particularly those interacting with groups of undergraduate and post-graduate trainees.

Clinical Clerkship↗
PubMed1993

[Clinical application of 11C-NMSP to the patients with pituitary adenoma other than prolactinoma].

The existence of dopamine D2 receptors in the pituitary adenoma is an important factor for bromocriptine therapy. In order to evaluate the D2 receptors in the pituitary adenoma, 11C-N-methylspiperone (NMSP) and positron emission tomography was performed in a variety of pituitary adenomas other than prolactinoma. Eight patients with pituitary adenoma including four non-functioning adenomas, two growth hormone (GH) secreting adenomas, one ACTH secreting adenoma and one TSH secreting adenoma and ten normal healthy volunteers were examined. 740 MBq of 11C-NMSP was injected and dynamic scan was performed from the time of injection to 80 min postinjection. The time dependent regional radioactivity in the striatum (st) and in the tumor tissue (tm) was measured and the binding rate, alpha, was calculated according to the following equation: Cst, tm/Ccbl = alpha x integral of t0 Ccbl dt/Ccbl + 1. The ratio of total radioactivity in the striatum or tumor over total activity in the cerebellum was plotted versus "normalized time", which was obtained by dividing integrated cerebellar radioactivity by actual cerebellar radioactivity for each timepoint. In three patients with pituitary adenoma, two scans were performed before and three hours after oral intake of 2.5 mg of bromocriptine. The alpha values for pituitary adenoma and normal striatum were 0.031 +/- 0.023 (0.017-0.088) and 0.042 +/- 0.006 (0.034-0.049), respectively. Bromocriptine reduced alpha value to various degree in pituitary adenoma (13-56%) but not in striatum (-3.7-3.3%). Our data suggests that in some of pituitary adenoma other than prolactinoma, dopamine D2 receptors existed but that nonspecific binding also contributed to the radioactivity in the tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1993

[Evaluation of the safety and clinical usefulness of a new myocardial imaging agent, 99mTc-PPN1011--multicenter phase II clinical trial report].

A new myocardial perfusion imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl phosphino]ethane (99mTc-PPN1011) was administered to 52 patients with various heart diseases each at rest and peak exercise on different days (Method A) and on the same day (Method B). The safety, optimal dosage, imaging procedures and the clinical usefulness were evaluated. No drug related adverse reactions were found. Image quality was considered adequate for diagnosis with as little as 185 MBq per injection, though the optimal dose range was 370-740 MBq. SPECT images were obtainable as early as 10 min, also until 3 hours after injection. There were no significant differences in clinical efficacy between method A and B, as well as sequential tests at rest and exercise. 99mTc-PPN1011 and 201T1 images in the same patient were compared segment by segment. Image quality of 99mTc-PPN1011 was significantly superior to that of 201T1. Analysis of images indicated that both agent were similar in diagnostic efficacy. It was concluded that 99mTc-PPN1011 is useful for myocardial perfusion imaging.

Adult↗
PubMed1992

[Gd-DTPA-enhanced MR imaging of the normal facial nerve].

We performed a prospective imaging study of the normal facial nerve within the temporal bone before and after injection of Gd-DTPA. The study included 29 patients using a 1.5T superconducting unit and 40 nerves (right: 21; left: 19) were available for analysis. There was no enhancement of the facial nerve within the internal auditory canal in the entire series. However, the enhancement at the labyrinthine segment was observed in one nerve (3%); at the geniculate ganglion in seven (18%); at the tympanic segment in 18 (45%) and at the mastoid segment in 28 nerves (70%). Our results indicate that enhancement of the facial nerve in normal subjects is not a rare condition.

Adolescent↗
PubMed1992

Pseudomyxoma peritonei with progressive calcifications: CT findings.

Development of abdominal calcifications due to pseudomyxoma peritonei is rare. The authors present three cases whereby computed tomographic (CT) studies during or after chemotherapy for pseudomyxoma peritonei demonstrated development and progression of punctate calcifications in the abdomen. The clinical and CT findings of these cases are presented together with a brief review of the pertinent literature.

Adult↗