[Effects of gravity on the gene expression of osteoclast differentiation factor and osteoclastogenesis inhibitory factor].
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Bone Marrow Cells↗
Biomedical subjects
A Sato
Publications and source records attributed to A Sato.
[A case of chorea-ballism with bilateral lesion of the corpus striatum and hyperglycemia].
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Aged↗
Virological and immunological features of long-term human immunodeficiency virus-infected individuals who have remained asymptomatic compared with those who have progressed to acquired immunodeficiency syndrome.
Infection with the human immunodeficiency virus (HIV) leads to a decrease in CD4(+) T cells and disease progression within a decade of seroconversion. However, a small group of infected people, despite being infected by HIV for 10 or more years, remain clinically asymptomatic and have stable CD4(+) cell counts without taking antiretroviral medication. To determine why these individuals, known as long-term survivors (LTS), remain healthy, the hematological profiles, viral load and properties, HIV coreceptor genotype, and anti-HIV immune responses of these people were compared with those of individuals who have progressed to disease (Progressors) over the same time period. Unlike Progressors, LTS have a low circulating viral load and a low number of HIV-infected cells. These differences in the levels of the viral load were not associated with a dominant biologic viral phenotype, varying growth kinetics of the virus, mutation in the cellular CCR5 gene, or the presence of neutralizing antibodies. Importantly, the difference in viral load could be explained by the enhanced ability of CD8(+) cells from LTS to suppress HIV replication.
Acquired Immunodeficiency Syndrome↗
Cancer cells overexpress mRNA of urokinase-type plasminogen activator, its receptor and inhibitors in human non-small-cell lung cancer tissue: analysis by Northern blotting and in situ hybridization.
The transcriptional localizations of urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitors (PAI-1 and PAI-2), which are possibly involved in cancer metastasis, have not been determined in human lung cancer. To identify their regulation in primary non-small-cell lung cancer, we assayed mRNA levels by Northern blot analysis in 25 cases and determined the localizations of mRNA by in situ hybridization in 10 cases. The amounts of uPA and PAI-2 mRNA were significantly higher in cancerous relative to normal lung tissues. However, no significant difference was observed in uPAR and PAI-1 mRNA levels. All transcripts were present in cancer cells and were predominantly located in tumor edges in several cases. In addition, PAI-1 transcripts were more abundant in poorly and moderately differentiated carcinomas relative to well-differentiated carcinomas and PAI-2 transcripts were more abundant in squamous cell carcinomas than in adenocarcinomas. Thus, PAIs may be involved in modulation of malignant potency. Our results indicate that human non-small-cell lung cancer cells can autonomously express the mRNAs of uPA, uPAR and PAIs, which are possibly involved in metastasis.
Adenocarcinoma↗
Regional correspondence between the ventral portion of the lumbar intervertebral disc and the groin mediated by a spinal reflex. A possible basis of discogenic referred pain.
STUDY DESIGN: Lumbar peripheral nerves were examined to determine whether they were responsive to electrical stimulation of the ventral portion of the lumbar disc in anesthetized rats. OBJECTIVES: To confirm by electrophysiologic means the neural correspondence between the ventral portion of the lumbar disc and the groin. SUMMARY OF BACKGROUND DATA: Patients with a degenerated lumbar disc occasionally report groin pain. However, its pathogenesis has not been investigated. The authors of the current study found that chemical stimulation of the ventral portion of rat lumbar disc caused cutaneous plasma extravasation in the groin, and thereby hypothesize the neural relation between the lumbar disc and the groin. METHODS: The ventral portion of rat L5-L6 disc was electrically stimulated, and the elicited action potentials were recorded from the iliohypogastric, genitofemoral, lateral femoral cutaneous, sural, and sciatic nerves. The roles of the lumbar sympathetic trunks and spinal cord in the generation of the action potentials were examined. RESULTS: Action potentials were elicited principally in the genitofemoral nerve; the action potentials of the genitofemoral nerve were not influenced by transection of the cervical spinal cord, whereas they disappeared immediately after death, which indicates that they are induced by a spinal reflex. The action potentials were reduced considerably after destruction of the lumbar sympathetic trunks, suggesting that they comprise an afferent path of the reflex. CONCLUSIONS: The ventral portion of the lumbar disc had spatial relation to the groin area via a spinal reflex. Such a relation suggests that a disorder in the ventral portion of the lumbar disc may be a possible source of groin referred pain.
Action Potentials↗
Preparation of difluoro analogs of CCGs and their pharmacological evaluations.
All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for metabotropic glutamate receptors (mGluRs).
Amino Acids, Dicarboxylic↗
Low carbohydrate intake before oral glucose-tolerance tests.
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Adult↗
A role of myofilament Ca2+ sensitivity in enhanced vascular reactivity in cardiomyopathic hamsters.
We compared the contractile responses to vasoconstrictors in aortas from 20- to 22-week old cardiomyopathic hamsters, BIO 53.58 strain, and age-matched F1b strain controls. Aortas from cardiomyopathic hamsters exhibited greater contractions in response to phenylephrine, angiotensin II, and high K+ than did the controls. Neither endothelium removal nor the presence of indomethacin and N(omega)-nitro-L-arginine (L-NNA) affected the enhanced contractile responses to these vasoconstrictors, indicating no involvement of endogenous prostanoids and nitric oxide from the endothelium. The contractile response to phorbol-12,13-dibutyrate (PDB) was also more markedly increased in cardiomyopathic aortas regardless of whether extracellular Ca2+ was present. The contractile response of cardiomyopathic aorta to phenylephrine was more sensitive to the inhibitory actions of the protein kinase C inhibitors staurosporine and calphostin C than was that of control aorta. These results suggest that activation of protein kinase C is partly involved in the enhanced phenylephrine response of cardiomyopathic aorta. None of nifedipine, ryanodine, and cyclopiazonic acid modified the maximum contractions induced by phenylephrine in either cardiomyopathic aortas or controls. The Ca2+ sensitivity of tension was significantly increased in beta-escin-skinned smooth muscle of mesenteric artery from cardiomyopathic hamsters compared to that of controls. PDB induced Ca2+ sensitization, but significantly only in cardiomyopathic hamsters. We propose that the enhanced vascular reactivity in cardiomyopathic hamsters may primarily result from increased Ca2+ sensitivity of contractile proteins. In addition, protein kinase C-mediated Ca2+ sensitization may further contribute to the enhanced vascular response to agonists.
Actin Cytoskeleton↗
Mutations in the E-domain of RAR portion of the PML/RAR chimeric gene may confer clinical resistance to all-trans retinoic acid in acute promyelocytic leukemia.
The binding of all-trans retinoic acid (ATRA) to the ligand-binding region in the E-domain of retinoic acid receptor-alpha modifies the transcriptional activity of RARalpha protein. ATRA probably induces differentiation of acute promyelocytic leukemia (APL) cells by binding to the E-domain of the RARalpha portion (RARalpha /E-domain) of PML/RARalpha chimeric protein. Therefore, molecular alteration in the RARalpha /E-domain of the chimeric gene is one mechanism by which patients with APL may acquire resistance to ATRA therapy. In this study using reverse transcription-polymerase chain reaction and single-strand conformation polymorphism, DNA segments amplified from the RARalpha /E-domain in fresh APL cells of 23 APL patients (8 males and 15 females from 4 to 76 years of age) were screened for mutations. Of those patients, 3 patients (1 with de novo and 2 with relapse) had clinical resistance to ATRA therapy. We found mutations in the RARalpha /E-domain of PML/RARalpha chimeric gene exclusively in the 2 patients who exhibited ATRA-resistance at relapse, whereas the mutations were not detected at their initial onset. Interestingly, these patients received a prolonged or intermittent administration of ATRA before relapse with ATRA-resistance. The mutations lead to the change of amino acid in the ligand-binding region of RARalpha /E-domain, Arg272Gln, or Met297Leu according to the amino acid sequence of RARalpha, respectively. Further study demonstrated that the in vitro ligand-dependent transcriptional activity of the mutant PML/RARalpha protein was significantly decreased as compared with that of wild-type PML/RARalpha. These findings suggest that mutations in the RARalpha /E-domain of the PML/RARalpha chimeric gene may confer clinical resistance to ATRA therapy in patients with APL.
Adolescent↗
Expression and purification of the extracellular ligand binding region of metabotropic glutamate receptor subtype 1.
Each metabotropic glutamate receptor possesses a large extracellular domain that consists of a sequence homologous to the bacterial periplasmic binding proteins and a cysteine-rich region. Previous experiments have proposed that the extracellular domain is responsible for ligand binding. However, it is currently unknown whether the extracellular ligand binding site can bind ligands without other domains of the receptor. We began by obtaining a sufficient amount of receptor protein on a baculovirus expression system. In addition to the transfer vector that encodes the entire coding region, transfer vectors that encode portions of the extracellular domain were designed. Here, we report a soluble metabotropic glutamate receptor that encodes only the extracellular domain and retains a ligand binding characteristic similar to that of the full-length receptor. The soluble receptor secreted into culture medium showed a dimerized form. Furthermore, we have succeeded in purifying it to homogeneity. Dose-response curves of agonists for the purified soluble receptor were examined. The effective concentration for half-maximal inhibition (IC50) of quisqualate for the soluble receptor was 3.8 x 10(-8) M, which was comparable to that for the full-length receptor. The rank order of inhibition of the agonists was quisqualate >> ibotenate >/= L-glutamate approximately (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid. These data demonstrate that a ligand binding event in metabotropic glutamate receptors can be dissociated from the membrane domain.
Animals↗
Cilostazol, a selective cAMP phosphodiesterase inhibitor, dilates retinal arterioles and increases retinal and choroidal blood flow in rats.
The effects of cilostazol, a selective cyclic AMP (cAMP) phosphodiesterase inhibitor, on retinal and choroidal blood flow and retinal arteriole diameter were examined in anesthetized rats. The retinal and choroidal blood flow was measured using laser Doppler flowmetry, and the diameter of the retinal arterioles was measured using digital video microscopy. Cilostazol was administered by two routes; systemically via the intravenous route, and directly into the retinal vessels via the intra-arterial route. When administered intravenously, 1 mg/kg of cilostazol produced a biphasic blood flow response, composed of an initial decrease which was dependent on a depressor response of mean arterial pressure, and a subsequent slight but significant increase which was independent of changes in mean arterial pressure. When administered intra-arterially over a 2-min period, 40-55 and 400-440 microg of cilostazol both produced an increase in the blood flow in a dose-dependent manner, while a depressor effect was observed only at the dose of 400-440 microg. The diameter of the retinal arterioles was increased after the intra-arterial injection of cilostazol (400 microg). It is concluded that intra-arterially administered cilostazol induces vasodilation of the retinal arterioles of rats, which results in an increase in blood supply to the retina, independent of changes in mean arterial pressure.
3',5'-Cyclic-AMP Phosphodiesterases↗
The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line: possible implications for the pathogenesis of AIDS.
Although apoptosis is considered one of the major mechanisms of CD4(+) T cell depletion in HIV-infected patients, the virus-infected cells somehow appear to be protected from apoptosis, which generally occurs in bystander cells. Vpr is an auxiliary HIV-1 protein, which, unlike the other regulatory gene products, is present at high copy number in virus particles. We established stable transfectants of CD4+ T Jurkat cells constitutively expressing low levels of vpr. These clones exhibited cell cycle characteristics similar to those of control-transfected cells. Treatment of control clones with apoptotic stimuli (i.e., cycloheximide/tumor necrosis factor alpha (TNF-alpha), anti-Fas antibody, or serum starvation) resulted in a massive cell death by apoptosis. In contrast, all the vpr-expressing clones showed an impressive protection from apoptosis independently of the inducer. Notably, vpr antisense phosphorothioate oligodeoxynucleotides render vpr-expressing cells as susceptible to apoptosis induced by cycloheximide and TNF-alpha as the control clones. Moreover, the constitutive expression of HIV-1 vpr resulted in the upregulation of bcl-2, an oncogene endowed with antiapoptotic activities, and in the downmodulation of bax, a proapoptotic factor of the bcl-2 family. Altogether, these results suggest that low levels of the endogenous vpr protein can interfere with the physiological turnover of T lymphocytes at early stages of virus infection, thus facilitating HIV persistence and, subsequently, viral spread. This might explain why apoptosis mostly occurs in bystander uninfected cells in AIDS patients.
Acquired Immunodeficiency Syndrome↗
Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T-tropic [correction of T cell-tropic] HIV-1 by three different monoclonal antibodies.
A chemokine receptor, CXCR-4, has been identified as an entry cofactor for T cell line-tropic (T-tropic) HIV-1. To detect expression of CXCR-4 at the single cell level and dissect postbinding events of HIV-1 infection, we generated three mAbs against human CXCR-4. These mAbs inhibited SDF-1-induced intracellular Ca2+ mobilization, and one of the mAbs immunoprecipitated a specific 47-kDa component from CXCR-4+ cells. Flow cytometric analysis showed that most human cell lines examined expressed CXCR-4. A fraction of normal PBMC expressed CXCR-4, but neutrophils were negative. Two-color analysis revealed that the majority of T cells, virtually all B cells, and all monocytes expressed CXCR-4, while it was only weakly present on NK cells. Thus, expression of CXCR-4 is not ubiquitous but cell type specific in hemopoietic cells. The three mAbs were shown to suppress cell fusion mediated by envelope proteins of a T-tropic NL432 virus but not by those of an M-tropic JRCSF virus Likewise, they suppressed infection of NL432 but not that of an M-tropic NL162 virus. In both cases it was noted that the suppressive activity varied considerably among the mAbs. These data confirmed that CXCR-4 is directly involved in env-mediated entry and fusion of T-tropic HIV-1 and suggest that the epitopes on CXCR-4 recognized by the three mAbs may have different roles in interaction with the envelope proteins of T-tropic HIV-1.
Animals↗
Topographical distribution of cells in the rat submandibular gland duct system with special reference to dark cells and tuft cells.
The duct system of the rat submandibular gland consists of the intercalated duct, the granular convoluted tubule, the striated duct, the excretory duct, the main excretory duct, and the salivary bladder. The duct system contains special cell types, such as dark cells and tuft cells, in addition to principal cells. However, little is known about cell distribution in the duct system. The purpose of the present study was to examine cell distribution and to perform a morphometric analysis of the duct system. Transmission and scanning electron microscopy were used to examine the duct system of the rat submandibular gland. Six regions in the duct system, the striated duct, the interlobular excretory duct, the 5-mm proximal excretory duct from the hilus, the main excretory duct at the hilus, the 10-mm distal main excretory duct from the hilus, and the salivary bladder, were investigated. Morphometric and statistical analyses of the data were then performed. The epithelium of the duct system consisted of a heterogeneous cell population. Dark cells and tuft cells were present throughout the duct system. The principal, dark, and tuft cells were distinguished by their different microvilli by using a scanning electron microscope. The frequency of these cells in the total epithelial cell population was as follows: The percentage of principal cells in the six regions of the duct system varied from 87.5% to 94.4%, that of dark cells varied from 4.1% to 7.2%, and that of tuft cells varied from 1.8% to 7.2%. The number of principal and tuft cells was significantly different between the striated duct and the main excretory duct at the hilus (P < 0.01). However, no significant difference in number of dark cells throughout the duct system was observed (P > 0.05). The abundance of the principal, dark, and tuft cells in the duct system of the rat submandibular gland was determined. Few tuft cells were distributed in the striated duct, and most were found at the hilus. Dark cells were distributed equally throughout the duct system.
Animals↗
Increasing frequency of occurrence of tuft cells in the main excretory duct during postnatal development of the rat submandibular gland.
Tuft cells, a widespread cell type that is present in the mucosal epithelia of hollow organs, including the main excretory duct (MED) epithelia of the rat salivary gland, are well documented morphologically. However, studies of their development are few. The purpose of the present study was to examine the perinatal and postnatal development of tuft cells in the main excretory duct of the rat submandibular gland. Main excretory ducts of the submandibular gland were obtained from five male Wistar rats at the ages of 0, 1, 7, 14, 17, 21, 23, 28, and 56 postnatal days and were prepared for scanning and transmission electron microscopy. The tuft cells, which are distinguished easily by their long microvilli protruding into the lumen, were recognizable first at 17 postnatal days. They showed a remarkable increase in number between 3 and 4 postnatal weeks. The percentages of tuft cells were 0.4% at 17 postnatal days and 0.8% at 3 postnatal weeks. The number of tuft cells represented approximately 5% of the total epithelial cells by 4 postnatal weeks. There was a significant difference between 3 and 4 postnatal weeks (P < 0.01). The microvilli of the tuft cells at the time of weaning had almost the same width as in the adult, but they were shorter. Microfilaments extending from the tips of the microvilli and microtubules and many electron-lucent vesicles in the supranuclear cytoplasm also were observed. These results indicate that tuft cells appeared in the MED of the submandibular gland during weaning and had abundant vesicles in their apical cytoplasm.
Animals↗
[A mitral valve reconstruction of infective endocarditis with brain abscess and intracranial mycotic aneurysm].
A case is reported of a brain abscess and an intracranial mycotic aneurysm associated with infective endocarditis caused by streptococcus intermedius. A 60-year-old man with a history of fever presented aphasia and right hemiparesis. A computed tomographic scan of the head revealed a low-density area with ring enhancement in the left parietal lobe consistent with a brain abscess. An angiography demonstrated an aneurysm on the distal branch of the middle cerebral artery compatible with a mycotic aneurysm. Doppler echo cardiography showed severe mitral regurgitation by chordal ruptures. The brain abscess and intracranial mycotic aneurysm were resolved under appropriate antibiotic therapy for eight weeks. Then, the mitral valve was reconstructed by replacement of the chordae tendineae with expanded polytetrafloroethylene suture and annuloplasty. The patient had no neurologic deficit except for paresthesia in the right hand, and had no mitral regurgitation at discharge.
Aneurysm, Infected↗
Fibroblasts as target and effector cells in Japanese patients with sarcoidosis.
Fibroblasts play a crucial role in progressive lung fibrosis, acting not only as target cells but also as effector cells. To clarify these functions in sarcoidosis, lung fibroblasts from Japanese sarcoid patients were studied for their proliferative capacity and cytokine productivity. Fibroblasts were cultured from transbronchial lung biopsy specimens from seven patients with sarcoidosis. As a comparison, fibroblasts from open lung biopsy specimens of four patients with idiopathic pulmonary fibrosis (IPF) were studied. For controls, fibroblasts were cultured from specimens of normal resected lung tissue of five patients with localized lung cancer. The proliferative activity of cultured fibroblasts from patients with sarcoidosis was highest among the three groups (p < 0.05). However, the proliferative capacity in all groups was suppressed when fibroblasts were cultured with interleukin-1beta (IL-1beta). No significant differences were noted in the degree of inhibition among the three groups. Addition of interferon-gamma (IFN-gamma) also resulted in inhibition of fibroblast growth in all groups, but the degree of inhibition was significantly greater in both the sarcoid and IPF groups than in controls (p < 0.05). The amount of interleukin-6 (IL-6) in the culture supernatants from sarcoid fibroblasts cocultured with IL-1beta was significantly higher than in controls. Sarcoid fibroblasts are not only proliferatively active but also possess effector cell function to produce cytokines. IL-6 may enhance the immunologic reaction to sarcoidosis and cause the disease to become chronic. IFN-gamma suppresses proliferation of sarcoid fibroblasts and may prevent fibrotic changes of the lungs in the Japanese sarcoid patients.
Adult↗
Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats.
In cats the global (gCBF) as well as the regional cerebral blood flow (rCBF) and blood pressure were measured before, during, and after noxious inward and outward rotations of normal and inflamed elbow joints. The animals were anesthetized with halothane and immobilized by gallamine triethiodide. The gCBF as well as the rCBF were measured using positron emission tomography (PET) with a camera specifically designed for use in small animals. Slow intravenous bolus injections of 15O-labeled water were followed by 3-min acquisition of regional radioactivity starting at the time of injection. In all experiments the gCBF as well as the blood pressure were increased by noxious inward-outward rotations of the normal and of the inflamed joint, whereas the blood pressure and the rCBF remained unchanged during bolus injections under control conditions (without any joint movement). Movements of the inflamed joint evoked significantly greater increases in blood pressure and gCBF than corresponding ones of the normal joint. These increases in gCBF were paralleled by increases in rCBF along the complete anterior to posterior axis of the brain. Again, the increases in rCBF were larger, more extensive and more uniform following the stimulation of the inflamed joint relative to the results obtained with stimulation of the normal joint. No significant laterality was seen, but when an atlas-based region of interest (ROI) analysis was carried out and when the individual variations in rCBF were removed with two-way ANOVA, significant differences were disclosed in rCBF between the stimulated condition and the resting condition in a large number of brain regions. In particular, noxious rotation of the normal (right) elbow joint induced a significant increase in rCBF over the cerebral cortex and in the right thalamus and hippocampus. The same stimulation of the (left) inflamed joint induced a significant increase in rCBF throughout the brain; the biggest increase being over the right posterior cortex. It is concluded that under the conditions of the present experiments the generally accepted autoregulation of the cerebral blood flow is not fully functioning, and various factors that may be responsible for this failure (which obscures rCBF differences) are discussed. The more pronounced increases in rCBF when moving inflamed joints instead of normal ones is thought to be a direct consequence of the peripheral sensitization of the articular nociceptors and the consequent central hyperexcitability induced in the articular nociceptive pathways.
Anesthesia↗