Search PubMed⌕ Search

Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 163 records · Page 9Linked to original sources
PubMed1997

Efferent targets of osseous CGRP-immunoreactive nerve fiber before and after bone destruction in adjuvant arthritic rat: an ultramorphological study on their terminal-target relations.

We report the ultramorphological characterization of the terminal-target relation of sensory peptidergic nerve fibers in healthy and diseased osseous tissues. Bone tissue sections were immunoelectronmicroscopically investigated for calcitonin gene-related peptide (CGRP), a neuropeptide widely distributed in sensory peptidergic fibers. Ultramorphological relation of the osseous CGRP-immunoreactive (ir) nerve terminals and their target cells was comparatively analyzed using healthy, arthritic, and postarthritic bone specimens from control and adjuvant-induced arthritic rats. Terminal-like profiles of the osseous CGRP-ir axons were evidenced in direct contact with the metaphyseal osteoblasts and osteoclasts of the control animals. Terminal-like profiles were also noted in the vicinity of the periosteal lining cells. Nonterminal-like profiles did not make intimate spatial relation to the cells/structures surrounding the nerve. Osseous CGRP-ir terminals and axons, which are either uncovered or thinly ensheathed by the supportive tissues, were extensively degenerated in adjuvant-induced infiltration, whereas larger fibers were relatively resistant. Numerous CGRP-ir axons with distinctive features reinnervated the postarthritic, ossifying periosteum. CGRP-ir axons appeared to reinnervate the eroded surface of metaphyseal bone and cartilage as early as the recruited osteoblasts resume osteogenesis in the postarthritic metaphysis. The observed terminal-target relations in the healthy and diseased bone tissues give an ultramorphological basis for the putative trophic, modulatory actions of CGRP innervation of the bone cells.

Animals↗
PubMed1997

Myocardial contractile reserve as prognostic determinant in patients with idiopathic dilated cardiomyopathy without overt heart failure.

To assess the prognostic significance of myocardial contractile reserve in patients with idiopathic dilated cardiomyopathy (DCM) without overt heart failure (New York Heart Association functional class I or II), seventy-one patients underwent exercise radionuclide angiography in addition to clinical, radiographic, hemodynamic, and echocardiographic evaluations. Myocardial contractile reserve was assessed as left ventricular ejection fraction (LVEF) during peak exercise minus LVEF at rest (delta LVEF). During an average of 49 months, 18 patients died of the disease. Cox's proportional-hazards regression analysis showed that the delta LVEF was the most powerful and independent discriminator for survival (p = 0.0002). Ejection time (p = 0.0029) and cardiothoracic ratio (p = 0.017) were the second and third most predictive variables, respectively. Evaluation of the delta LVEF, which reflects residual myocardial contractile reserve, can provide important information about the prognosis of patients with DCM and mild symptoms.

Adolescent↗
PubMed1997

[Virological studies on Epstein-Barr virus-positive gastric carcinoma].

An increasing number of reports have suggested the association of Epstein-Barr virus (EBV) with a subpopulation of gastric adenocarcinomas, mainly based on the PCR, in situ hybridization and Southern blot studies. Further virological and immunological analyses revealed that latent EBV gene expression in EBV-positive gastric carcinoma is highly selective and thus more closely resembles that in Burkitt's lymphoma than the majority of nasopharyngeal carcinomas, which would be advantageous for the tumor cells to evade effective virus-specific immunity. On the basis of data including ours, the possible EBV infection and oncogenic mechanisms of normal gastric epithelia are also discussed.

Adenocarcinoma↗
PubMed1997

[Clinical, phenotypic and genotypic aspects of nasal T-cell lymphoma and its causal association with Epstein-Barr virus].

The authors reviewed the clinical, phenotypic, genotypic, and Epstein-Barr virus (EBV)-findings of 18 patients with nasal T-cell lymphoma(NTL). The clinical features were characterized as prolonged fever, widespread dissemination into distant sites, and poor prognosis with median survival of only 6 months. EBV-encoded small nuclear early region(EBER) transcripts were identified in 16 of 18 patients. Monoclonal EBV genome, EBV-encoded nuclear antigen(EBNA)-1, and latent membrane protein(LMP)-1 were also detected in all EBER-positive cases tested. All EBV-positive NTL showed coexpression of natural killer(NK) cell phenotype CD56 and CD2. Of 9 EBV-positive NTL, seven cases expressed T-cell receptor (TCR)-delta chain with rearranged beta-, gamma- and/or delta- genes. These data suggest that some cases of EBV-positive NTL may be derived from the lineage of NK-like T-cells or gamma delta T-cells, and that EBV may play a role in the lymphomagenesis.

Adult↗
PubMed1997

Time series analysis of the course of Menière's disease.

Subjective symptoms of Menière's disease (vertiginous attacks, nonparoxysmal dizziness, tinnitus, hearing loss, headache, stiff neck, nausea etc.) were graded respectively according to severity (0-3 or 0-5) and were recorded daily by affected patients. These recordings, from 20 cases of Menière's disease, were collected and analysed by an original program of time series analysis including autocorrelation, cross-correlation, daily sum of inner ear related factors and general factors, and their moving average. Cluster occurrence of dizzy spells in the active stage and a marked cross-correlation between inner ear factors and general factors were found to constitute a characteristic pattern in Menière's disease in relation to its pathophysiology. Time series analysis was also useful for clinical decision-making, such as evaluation of the effect of treatment, and estimation of prognosis.

Anti-Inflammatory Agents↗
PubMed1997

Ultrastructure of the synovial sensory peptidergic fibers is distinctively altered in different phases of adjuvant induced arthritis in rats: ultramorphological characterization combined with morphometric and immunohistochemical study for substance P, calcitonin gene related peptide, and protein gene product 9.5.

OBJECTIVE: To characterize sequential ultramorphological changes in synovial sensory peptidergic fibers in different phases of adjuvant induced arthritis. METHODS: Topographically defined regions of the tarsal joints from arthritic rats were evaluated 7, 10, 14, and 21 days after inoculation with Freund's adjuvant. Peptidergic fibers were identified by high resolution video microscope, then fibers containing calcitonin gene related peptide (CGRP) were visualized by electron microscopy. Morphometric quantification of synovial fibers immunohistochemically stained for CGRP, substance P (SP), and protein gene product 9.5 (PGP 9.5) was done at this time. RESULTS: The control synovial lining contained numerous ramified axon terminals, whereas the sublining contained mostly nerve fiber bundles, except for axon terminals visible around the blood vessels. In arthritis, on Day 14, there were few immunoreactive nerve fibers and terminals. Instead, electron microscopy disclosed numerous activated and/or degenerated axons [CGRP: 2973 +/- 345 vs 495 +/- 288; SP: 657 +/- 344 vs 199 +/- 60; PGP 9.5: 4473 +/- 944 vs 886 +/- 299, all p < 0.05 (units: microm/mm2)]. On Day 21 CGRP and PGP 9.5 immunoreactive fibers were numerous again (4892 +/- 551 and 3613 +/- 1350, respectively), but SP immunoreactive nerve fibers did not seem to regenerate (126 +/- 44). Regenerating nerve fibers had a distinctive ultrastructure and they were always seen in association to Schwann cells. CONCLUSION: The healthy synovial lining is innervated by peptidergic nerve terminals. During the inflammatory phase of arthritis neuropeptides are locally released due to stimulation and degeneration of the axons. The apparently unaffected Schwann cells seem to play a pivotal role in subsequent regeneration of peptidergic axons. However, the ultrastructure and the neuropeptide content (and probably the function) of the regenerating axons are different from those of the normal synovial nerve fibers.

Animals↗
PubMed1997

[Quantitative measurements of regional cerebral blood flow using technetium-99m-L,L-ECD SPECT activated with acetazolamide: fundamental study of measurement's accuracy, comparison with 123I-IMP ARG method].

We measured regional cerebral blood flow before and after acetazolamide administration using a serial noninvasive method with 99mTc-ECD developed by Matsuda and Takeuchi et al., and compared the accuracy of measured values with those obtained by the conventional 123I-IMP ARG method. When the regional cerebral blood flow was measured for 80 brain regions in 5 subjects without scatter correction, a differential of 0.5 +/- 8.4% was obtained between values measured before and after physiological saline administration as a placebo. A differential of -0.2 +/- 12.6% was obtained when the same regions were measured with scatter correction. These findings indicated that placebo administration did not affect measured values, regardless of whether scatter correction was performed. When 64 regions in 4 subjects at rest were measured on two successive days, a differential of -1.1 +/- 9.0% was obtained between the values measured on the two days. A differential of -4.0 +/- 11.7% was obtained for the same regions following acetazolamide administration. These findings showed that measurements were reproducible both when subjects were at rest and when they were administered acetazolamide. The above two methods were used for measurement of 80 brain regions in the same 5 subjects for comparison. Measurements of subjects at rest and with acetazolamide administration were performed on separate days. The regression line y = 0.99x + 1.47, r = 0.80, was obtained for the subjects at rest, and y = 0.86x + 7.76, with r = 0.76, for the subjects following acetazolamide administration. These findings demonstrated a good correlation between the values obtained using the two methods. The values obtained using the method of Matsuda and Takeuchi et al., before and after acetazolamide administration were thus consistent with those reported previously using the conventional method, and the former method proved to be both simple and reliable.

Acetazolamide↗
PubMed1997

[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics].

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Adolescent↗
PubMed1996

Cervical myelopathy caused by calcium pyrophosphate dihydrate crystal deposition in facet joints. A case report.

STUDY DESIGN: This report illustrates a case of cervical myelopathy caused by degenerative changes of the facet joints in which calcium pyrophosphate dihydrate crystals were found histologically. OBJECTIVES: To evaluate the treatment of this patient, which involved the principles of laminoplasty and posterolateral fusion, and to analyze surgical specimens and preoperative radiographs taken after the patient's surgery. SUMMARY OF BACKGROUND DATA: Calcium pyrophosphate dihydrate deposition occurs in cartilage, ligaments, tendons, and joint capsules. Radiographic changes of the cervical facet joints caused by such deposition have already been reported in cadaveric studies. Cases with neurologic compromise rarely occur. METHODS: Surgical specimens that were obtained from the cervical facet joints, i.e., capsule and synovium, were analyzed histopathologically. RESULTS: The preoperative radiographic study showed severe degenerative changes of the cervical facet joints, and analysis of the surgical specimens indicated the presence of calcium pyrophosphate dihydrate crystals. CONCLUSIONS: The cervical facet joints can be involved in calcium pyrophosphate dihydrate crystal deposition and this involvement may accelerate the degenerative changes of the facet joints.

Adult↗
PubMed1996

Translocation of diacylglycerol kinase alpha to the nuclear matrix of rat thymocytes and peripheral T-lymphocytes.

The cytosolic alpha-diacylglycerol kinase (DGK) was translocated to and tightly associated with the nuclear matrix when rat thymocytes and peripheral T-lymphocytes were stimulated with concanavalin A or anti-T-cell receptor antibody. This translocation occurred rather slowly and was completed in 3-4 h after cell stimulation. We also detected significant accumulation of nuclear phosphatidic acid interpreted as being formed by the translocated enzyme. The enzyme translocation is not directly linked to phosphoinositide turnover and protein phosphorylation, since phorbol myristate acetate and calcium ionophore did not affect the cellular DGK alpha and since we detected no covalent modification of the enzyme molecule. Although the mechanisms underlying the enzyme translocation remain unknown, our results indicate that DGK alpha participates in nuclear phospholipid metabolism occurring at the intermediate stage of lymphocyte activation.

Animals↗
PubMed1996

The C-terminal part of diacylglycerol kinase alpha lacking zinc fingers serves as a catalytic domain.

All mammalian diacylglycerol kinase (DGK) isoenzymes so far cloned consist of four conserved regions, namely, C1, C2 (tandem EF-hand structures), C3 (tandem cysteine-rich zinc finger sequences) and the C-terminal C4 domains. To determine the catalytic domain we expressed in COS-7 cells various truncation mutants of pig DGK alpha and assessed their enzyme activities. We found that the C4 domain lacking the whole N-terminal region including the zinc fingers possessed DGK activity that was dependent on the concentrations of diacylglycerol and ATP very similarly, as did the wild-type DGK alpha. Furthermore the DGK activity of the wild-type DGK and that expressed by the C4 domain were similarly activated by anionic amphiphiles such as phosphatidylserine, phosphatidylinositol and deoxycholate. It was also shown that a DGK mutant consisting of the zinc fingers and the C4 domain has enzymological properties very similar to those expressed by the C4 domain alone. We also confirmed that the intact DGKs alpha, beta and gamma expressed in COS-7 cells displayed no detectable phorbol ester binding. These results show that the C4 domain of DGK is the catalytic region that is responsible for the enzyme activities sensitive to different activators. We cannot exclude the possibility that the N-terminal portion including the zinc fingers can still interact with diacylglycerol and activators without affecting the enzyme activity measured in vitro. However, it is quite likely that the DGK zinc fingers do not serve as diacylglycerol-binding sites, in contrast with those present in other proteins such as protein kinases C and n-chimaerin. Site-directed mutagenesis of all six putative ATP binding sites (Lys248, Lys383, Lys395, Lys483, Lys492, and Lys554) did not significantly affect the enzyme activity. We therefore suggest that DGK does not contain a typical P-loop of ATP binding sites.

Amino Acid Sequence↗
PubMed1996

Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes. Polymerase chain reaction amplification of mouse H2O2-inducible hic53 clone yielded the cDNA encoding phosphatidic acid phosphatase.

We previously described the purification of an 83-kDa phosphatidic acid phosphatase (PAP) from the porcine thymus membranes (Kanoh, H., Imai, S.-i., Yamada, K. and Sakane, F.(1992) J. Biol. Chem. 267, 25309-25314). However, we found that a minor 35-kDa protein could account for the PAP activity when the purified enzyme preparation was further analyzed. We thus determined the N-terminal sequence of the 35-kDa candidate protein and prepared antipeptide antibody against the determined sequence, MFDKTRLPYVALDVL. The antibody almost completely precipitated the purified enzyme activity. Furthermore, the antibody precipitated from the radioiodinated enzyme preparation a single 35-kDa protein, which was converted to a 29-kDa form when treated with N-glycanase. We also found that the immunoprecipitable PAP activity was exclusively associated with the plasma membranes of porcine thymocytes. These results indicated that the 35-kDa glycosylated protein represents the plasma membrane-bound (type 2) PAP. We surprisingly noted that the N-terminal sequence of the porcine PAP was almost completely conserved in the internal sequence encoded by a mouse partial cDNA clone, hic53, reported as a H2O2-inducible gene (Egawa, K., Yoshiwara, M., Shibanuma, M., and Nose, K.(1995) FEBS Lett. 372, 74-77). We thus amplified from the mouse kidney RNA the hic53 clone by polymerase chain reaction, and obtained a cDNA encoding a novel protein of 283 amino acid residues with a calculated Mr of 31,894. Methionine reported as an internal residue was found to serve as an initiator, and the C-terminal 64 residues were lacking in hic53. The protein contains several putative membrane-spanning domains and two N-glycosylation sites. When transfected into 293 cells, the cDNA gave more than 10-fold increase of the membrane-bound PAP activity, which could be precipitated by the antipeptide antibody. In [35S]methionine-labeled cells, the translational product was confirmed to be a 35-kDa protein, which became 30 kDa in cells treated with tunicamycin, an inhibitor of N-glycosylation. We thus succeeded first in identifying the porcine type 2 PAP and subsequently in determining the primary structure of a mouse homolog of the PAP.

Amino Acid Sequence↗
PubMed1996

Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success.

BACKGROUND: Typical atrial flutter (AFL) results from right atrial reentry by propagation through an isthmus between the inferior vena cava (IVC) and tricuspid annulus (TA). We postulated that the eustachian valve and ridge (EVR) forms a line of conduction block between the IVC and coronary sinus (CS) ostium and forms a second isthmus (septal isthmus) between the TA and CS ostium. METHODS AND RESULTS: Endocardial mapping in 30 patients with AFL demonstrated atrial activation around the TA in the counter-clockwise direction (left anterior oblique projection). Double atrial potentials were recorded along the EVR in all patients during AFL. Pacing either side of the EVR during sinus rhythm also produced double potentials, which indicated fixed anatomic block across EVR. Entrainment pacing at the septal isthmus and multiple sites around the TA produced a delta return interval < or = 8 ms in 14 of 15 patients tested. Catheter ablation eliminated AFL in all patients by ablation of the septal isthmus in 26 patients and the posterior isthmus in 4. AFL recurred in 2 of 12 patients (mean follow-up, 33.9 +/- 16.3 months) in whom ablation success was defined by the inability to reinduce AFL, compared with none of 18 patients (mean follow-up, 10.3 +/- 8.3 months) in whom success required formation of a complete line of conduction block between the TA and the EVR, identified by CS pacing that produced atrial activation around the TA only in the counterclockwise direction and by pacing the posterior TA with only clockwise atrial activation. CONCLUSIONS: (1) The EVR forms a line of fixed conduction block between the IVC and the CS; (2) the EVR and the TA provide boundaries for the AFL reentrant circuit; and (3) verification of a complete line of block between the TA and the EVR is a more reliable criterion for long-term ablation success.

Adult↗
PubMed1996

Nasal T-cell lymphoma causally associated with Epstein-Barr virus: clinicopathologic, phenotypic, and genotypic studies.

BACKGROUND: The authors have previously demonstrated nasal T-cell lymphoma (NTL) associated with Epstein-Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified. METHODS: The study group consisted of 18 patients with NTL. The phenotype was determined by immunoperoxidase staining with various monoclonal antibodies. Genotypic study was done using Southern blot hybridization. The presence of EBV-encoded small nuclear early region (EBER) RNA and EBV DNA were determined by in situ hybridization. The expression of EBV-encoded nuclear antigen (EBNA) and latent membrane protein (LMP1) were identified by immunohistologic methods. Clonotypic analysis of EBV genomes was performed by Southern blot hybridization with EBV termini fragment probe. RESULTS: The clinical features of NTL were characterized as prolonged fever (16 patients), widespread dissemination into distant sites (13 patients), and poor prognosis with a median survival of only 6 months. EBER transcripts were identified in 16 of 18 patients. Monoclonal EBV genomes EBNA1 and LMP1 were also detected in all EBER-positive cases tested. All 18 patients expressed pan-T antigens such as MT1, CD45RO, and/or CD2. The rearrangements of T-cell receptor (TCR)-beta, -gamma, and/or -delta genes were shown in all 11 patients tested. The natural killer (NK) cell phenotype CD56 was expressed in all EBV-positive cases tested, and was not detected in EBV-negative cases. Seven EBV-positive cases expressed a TCR-delta chain with rearranged TCR-gamma or -delta genes whereas both EBV-negative cases corresponded to alpha beta T-cell lymphoma, which expressed a TCR-beta chain with a rearranged TCR-beta gene. CONCLUSIONS: These data suggest that EBV-positive NTL may be derived from the lineage of NK-like T-cells or gamma delta T-cells, and that EBV may play a role in lymphomagenesis. Therefore, we propose that NTL which has peculiar clinical and histologic features could be classified as a new lymphoma entity.

Adult↗
PubMed1996

Isolation and characterization of vascular smooth muscle inositol 1,4,5-trisphosphate receptor.

myo-Inositol 1,4,5-trisphosphate (InsP3) receptor of porcine aorta was purified to near homogeneity and its biochemical properties were compared with those of cerebellar InsP3 receptor of the same animal species. The aortic InsP3 receptor consisted of equal amounts of two polypeptides with slightly differing molecular masses of around 240 kDa and was found to possess a single population of InsP3-binding site (Kd of 1.2 nM). The InsP3 receptor purified from porcine cerebellum was also comprised of two polypeptides. However, the molecular mass was slightly but definitely larger, being 250 kDa, and the amounts of the two polypeptides were not equal. The aortic InsP3 receptor cross-reacted with polyclonal antibody specific to type 1 InsP3 receptor as did the cerebellar InsP3 receptor. The aortic InsP3 receptor bound to calmodulin-Sepharose in a Ca(2+)-dependent manner, while the cerebellar InsP3 receptor did not. Reverse transcriptase-PCR analysis revealed two splicing variants of the type 1 InsP3 receptor in porcine aortic smooth muscle distinct from those of the type 1 InsP3 receptor of porcine cerebellum. The possible relevance of this difference to difference in calmodulin-binding property was discussed.

Amino Acid Sequence↗
PubMed1996

Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-beta.

We studied a cell-cell interaction via transforming growth factor-beta (TGF-beta ) between liver stellate cells (SCs) and parenchymal cells (PCs) using co-cultures of rat primary SCs and PCs. Both TGF-beta added exogenously to the culture medium, and TGF-beta produced endogenously from SCs after stimulation with retinoic acid (RA), suppressed the production and secretion of albumin from PCs. This effect occurred at the translational level, but not at the transcriptional level; TGF-beta, as well as SC culture medium conditioned by RA, did not affect the albumin mRNA levels, but decreased the biosynthesis of [35-S]methionine-labeled albumin without altering its post-translational degradation rate. These results suggest that TGF-beta generated from SCs facilitates the development of liver cirrhosis not only by inducing the production of fibrotic components from SCs, but also by impairing the function of the surrounding PCs.

Albumins↗
PubMed1996

Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases.

A fourth member of the diacylglycerol kinase (DGK) gene family termed DGK delta was cloned from the human testis cDNA library. The cDNA sequence contains an open reading frame of 3,507 nucleotides encoding a putative DGK protein of 130,006 Da. Interestingly, the new DGK isozyme contains a pleckstrin homology domain found in a number of proteins involved in signal transduction. Furthermore, the C-terminal tail of this isozyme is very similar to those of the EPH family of receptor tyrosine kinases. The primary structure of the delta-isozyme also has two cysteine-rich zinc finger-like structures (C3 region) and the C-terminal C4 region, both of which have been commonly found in the three isozymes previously cloned (DGKs alpha, beta and gamma). However, DGK delta lacks the EF-hand motifs (C2) and contains a long Glu- and Ser-rich insertion (317 residues), which divides the C4 region into two portions. Taken together, these structural features of DGK delta indicate that this isozyme belongs to a DGK subfamily distinct from that consisting of DGKs alpha, beta, and gamma. Increased DGK activity without marked preference to arachidonoyl type of diacylglycerol was detected in the particulate fraction of COS-7 cells expressing the transfected DGKdelta cDNA. The enzyme activity was independent of phosphatidylserine, which is a common activator for the previously sequenced DGKs. Northern blot analysis showed that the DGK delta mRNA (approximately 6.3 kilobases) is most abundant in human skeletal muscle but undetectable in the brain, thymus, and retina. This expression pattern is different from those of the previously cloned DGKs. Our results show that the DGK gene family consists of at least two subfamilies consisting of enzymes with distinct structural characteristics and that each cell type probably expresses its own characteristic repertoire of DGKs whose functions may be regulated through different signal transduction pathways.

Amino Acid Sequence↗