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PubMed2006

Exploring and expanding the structural diversity of self-assembling dendrons through combinations of AB, constitutional isomeric AB2, and AB3 biphenyl-4-methyl ether building blocks.

General, efficient and inexpensive methods for the synthesis of dendritic building blocks methyl 3',4'-dihydroxybiphenyl-4-carboxylate, 3',5'-dihydroxybiphenyl-4-carboxylate, and methyl 3',4',5'-trihydroxybiphenyl-4-carboxylate were elaborated. In all syntheses the major step involved an inexpensive Ni(II)-catalyzed Suzuki cross-coupling reaction. These three building blocks were employed together with methyl 4'-hydroxybiphenyl-4-carboxylate in a convergent iterative strategy to synthesize seven libraries containing up to three generations of 3',4'-, 3',5'-, and 3',4',5'-substituted biphenyl-4-methyl ether based amphiphilic dendrons. These dendrons self-assemble into supramolecular dendrimers that self-organize into periodic assemblies. Structural and retrostructural analysis of their assemblies demonstrated that these dendrons self-assemble into hollow and non-hollow supramolecular dendrimers exhibiting dimensions of up to twice those reported for architecturally related dendrons based on benzyl ether repeat units. These new dendrons expand the structural diversity and demonstrate the generality of the concept of self-assembling dendrons based on amphiphilic arylmethyl ethers.

Journal Article↗
PubMed2006

Expression and role of MHC class I-related chain in myeloma cells.

BACKGROUND: The molecular mechanism of natural killer (NK) cell cytotoxicity to myeloma cells remains unclear. We investigated whether MHC class I-related chain (MIC), a ligand of NKG2D that is an activating NK cell receptor, is involved in the cytotoxicity of NK cells toward myeloma cells, and examined the effects of various drugs on the cytotoxicity. METHODS: Two human myeloma cell lines and fresh myeloma cells from 10 patients were used. MIC expression was examined by flow cytometry and reverse transcription (RT)-PCR. NK cell cytotoxicity was examined using a 51Cr-release assay. The effects of various drugs, including thalidomide, all-trans retinoic acid, dexamethasone, IFN-alpha and incadronate, on the MIC expression and NK cell cytotoxicity were examined. RESULTS: MIC was highly expressed on the human myeloma cell lines U266 and RPMI-8226 and in myeloma cells of one of 10 patients examined. MIC expression on these cells was not changed by various drugs except IFN-alpha, by which MIC expression was down-regulated. Although MIC and HLA class I molecules were similarly expressed at high levels on both cell lines, U266 was sensitive to NK cells whereas RPMI-8226 was not. Furthermore, cytolysis by NK cells was not inhibited by the addition of anti-MIC Ab or decreased expression of MIC caused by IFN-alpha. DISCUSSION: MIC plays a role in the cytolysis by NK cells in multiple myeloma.

Angiogenesis Inhibitors↗
PubMed1999

Potential usefulness of 18F-2-fluoro-deoxy-D-glucose positron emission tomography in cervical compressive myelopathy.

STUDY DESIGN: This case study describes the usefulness of high-resolution 18F-2-fluoro-deoxy-D-glucose (18FDG)-positron emission tomography (PET) for metabolic neuroimaging of the cervical spinal cord in patients with compressive myelopathy. OBJECTIVE: To examine whether 18FDG-PET imaging could visualize deterioration of cervical spinal cord function associated with a variable degree of compression and to determine its potential usefulness during assessment of myelopathy. SUMMARY OF BACKGROUND DATA: A few studies have described the use of 18FDG-PET imaging in cervical cord diseases, but visualization of the cervical spinal cord before and after surgical decompression for compressive myelopathy has not been reported. The potential usefulness of 18FDG-PET imaging for assessment of the function of compressed cervical cord has not been discussed previously. METHODS: An 18FDG-PET scan was performed before and after surgery in seven patients with cervical compressive myelopathy. The correlation between the metabolic rate of glucose of the cervical spinal cord and neurologic scores was evaluated. The metabolic rate of glucose in different vertebral levels was also measured. RESULTS: Preoperative metabolic rate of glucose was high in two patients but low in the other five. At the time of the second postoperative examination, metabolic rate of glucose was higher in six of the seven patients, and the increase was associated with neurologic improvement. Use of 18FDG was not related to changes in signal intensities on T2-weighted magnetic resonance images. The metabolic rate of glucose decreased at the affected vertebral level in four patients, increased in two, and did not change in one, relative to the unaffected levels. CONCLUSIONS: High-resolution 18FDG-PET neuroimaging may provide clinically useful qualitative and quantitative estimation of impaired metabolic activity of the compromised cervical spinal cord in compressive myelopathy. 18FDG-PET images may also offer additional information related to neuronal dysfunction induced by mechanical compression.

Adult↗
PubMed2007

Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.

OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

Angina Pectoris↗
PubMed2004

Preoperative stellate ganglion blockade prevents tourniquet-induced hypertension during general anesthesia.

BACKGROUND: Prolonged and excessive inflation of pneumatic tourniquets leads to a hyperdynamic circulatory response. Sympathomimetic activity is an important factor in tourniquet-induced hypertension. Stellate ganglion block specifically blunts sympathetic efferent nerves and prevents hypertension induced by sympathomimetic stimulation. The present study was performed to investigate the effects of stellate ganglion block (SGB) on arterial pressure and heart rate during prolonged tourniquet use under general anesthesia. METHODS: Twenty patients scheduled for knee arthroscopy were either treated with 10 ml of 1% lidocaine for SGB (SGB group; n = 10), or intramuscular injection (IM group; n = 10) before tourniquet inflation. Comparisons of systolic and diastolic arterial pressure and heart rate were made before and after the induction of anesthesia, 10 min after the lidocaine treatment, every 5 min during the first 60 min after tourniquet inflation, and immediately before and 5 min following deflation. The maximum values of the circulatory variables were compared. RESULTS: Tourniquet inflation caused increases in the circulatory variables in both groups. Systolic arterial pressure in the SGB group was significantly lower than that in the IM group after 55 min of tourniquet inflation. Diastolic arterial pressure also was significantly lower in the SGB group immediately before the deflation. The maximum values of the three hemodynamic variables were significantly lower in the SGB group. Arterial pressure significantly decreased after tourniquet deflation in the IM group. CONCLUSION: Ipsilateral SGB attenuated the hyperdynamic response mediated by prolonged tourniquet inflation during knee arthroscopy.

Adult↗
PubMed2006

Prevalence of osteoarthritis, osteoporotic vertebral fractures, and spondylolisthesis among the elderly in a Japanese village.

PURPOSE: To study the prevalence of osteoarthritis, osteoporotic vertebral fractures, and spondylolisthesis among elderly residents of a Japanese village and to examine the correlation between radiographic evidence of abnormality and lower back pain. METHODS: 205 men (mean age, 70.7 years) and 323 women (mean age, 70.5 years) in a Japanese village participated in this cross-sectional study. Plain lateral radiographs were taken from the lower thoracic spine to the sacral spine. They were evaluated by 3 independent orthopaedic surgeons for degree of osteoarthritis (using Weiner grading system) and the presence of osteoporotic vertebral fractures and spondylolisthesis. RESULTS: The prevalence of osteoarthritis in elderly Japanese villagers was 38.3%, whereas that of osteoporotic vertebral fractures and spondylolisthesis was 17.8% and 8.9%, respectively. There was no significant difference in osteoarthritis between men and women, but osteoporotic vertebral fractures and spondylolisthesis were significantly more common in females (p<0.01). No significant correlation was observed between lower back pain and radiographic evidence of degenerative spinal disease. CONCLUSION: The prevalence of spondylolisthesis in elderly Japanese was much lower than that in whites or African Americans. The prevalence of osteoarthritis or osteoporotic vertebral fractures was comparable with other English or US studies. Radiographic evidence of osteoarthritis, osteoporotic vertebral fractures, and spondylolisthesis is not necessarily associated with lower back pain.

Aged↗
PubMed1998

Effect of YM087, a potent nonpeptide vasopressin antagonist, on vasopressin-induced protein synthesis in neonatal rat cardiomyocyte.

OBJECTIVE: Hypertrophy of cardiomyocytes may play an important role in the pathogenesis of cardiac hypertrophy associated with various cardiovascular diseases such as congestive heart failure. The aim of this study was to investigate whether vasopressin (AVP) induces protein synthesis in cultured neonatal rat cardiomyocytes through its specific receptor and whether YM087, a newly synthesized nonpeptide AVP receptor antagonist, inhibits AVP-induced protein synthesis in vitro. METHODS: AVP receptors on cardiomyocytes were characterized using the radioligand [3H] AVP. The effects of AVP and YM087 on intracellular free calcium concentration ([Ca2+]i), mitogen-activated protein (MAP) kinase and [3H]-leucine incorporation were investigated in cultured neonatal rat cardiomyocytes. RESULTS: In cardiomyocytes, Scatchard analysis showed a single population of high-affinity binding sites with the expected AVP V1A receptor subtype profile. YM087 showed high affinity for cardiomyocyte V1A receptors with a Ki value of 0.63 nM. In these same cells, YM087 potently inhibited AVP-induced increases in [CA2+]I and activation of MAP kinase in a concentration-dependent manner. In addition, AVP concentration-dependently stimulated the synthesis of protein without changing the rate of DNA synthesis, and YM087 prevented AVP-induced protein synthesis in a concentration-dependent manner. CONCLUSIONS: These results suggest that AVP directly causes protein synthesis and YM087 is a potent inhibitor of AVP-induced protein synthesis of cardiomyocytes and thus may have beneficial effects in the development and regression of cardiomyocytic hypertrophy.

Analysis of Variance↗
PubMed2000

Liver-infiltrating CD56 positive T lymphocytes in hepatitis C virus infection.

AIM: Hepatitis C virus (HCV) is a major cause of post-transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus-specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV-infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56+ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH-C). MATERIAL AND METHODS: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH-C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. RESULTS: The CD56+ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly gamma delta-TCR. There was a correlation between the ratio of CH-C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. CONCLUSION: The correlation between CD56+ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver-infiltrating CD56+ T lymphocytes play an important pathologic role in hepatocellular injury in CH-C.

Adult↗
PubMed1998

Expression of alpha-fetoprotein and prostate-specific antigen genes in several tissues and detection of mRNAs in normal circulating blood by reverse transcriptase-polymerase chain reaction.

BACKGROUND: alpha-Fetoprotein (AFP) and prostate-specific antigen (PSA) in serum are widely used as tumor markers in the evaluation of prognosis and management of patients with hepatocellular carcinoma and prostate cancer, respectively. To establish the molecular diagnosis of cancer, reverse transcriptase polymerase chain reaction (RT-PCR) for AFP and PSA was used to identify circulating cancer cells in the blood of cancer patients. Here, we examined the tissue-specificity of AFP and PSA and tested whether AFP and PSA are suitable targets in the detection of certain cancer cells by RT-PCR using peripheral blood samples. METHODS: Tissue specificity of AFP and PSA was analyzed by Northern blotting and RT-PCR. Probes for AFP and PSA were hybridized with poly A+ RNAs from 50 human tissues. RT-PCR for AFP and PSA mRNA was performed using several cancerous tissues and normal tissues and peripheral blood cells from seven healthy volunteers. RESULTS: Broad expression of AFP was observed in several tissues and a large amount of AFP mRNA was found in fetal liver. PSA was expressed in prostate, salivary gland, pancreas and uterus. By RT-PCR, AFP and PSA mRNA were detected in several tumors, including salivary pleomorphic adenoma, hilar bile duct carcinoma, pancreatic carcinoma, transitional cell carcinoma of urinary bladder and thyroid papillary carcinoma. Furthermore, AFP and PSA mRNAs were frequently detected by RT-PCR, even in peripheral blood cells from healthy volunteers. CONCLUSIONS: Neither AFP nor PSA showed tissue-specific expression. AFP and PSA mRNA were detected in several diseased and non-diseased tissues and normal circulating blood by RT-PCR.

Adenoma, Pleomorphic↗
PubMed2004

An increased adjuvanticity of liposomes by the inclusion of phosphatidylserine in immunization with surface-coupled liposomal antigen.

BACKGROUND: Exposure of phosphatidylserine (PS) on apoptotic cells is known to result in the enhanced recognition of apoptotic cells by phagocytes. By the inclusion of PS in the lipid component of liposomes, increased liposome immune adjuvant activity was expected. METHODS: In the present study, two different liposome preparations containing either PS, i.e. PS-liposome, or phosphatidylcholine (PC), i.e. PC-liposome, were made, and macrophage recognition, processing, and antigen presentation of surface-coupled liposomal antigen were compared. RESULTS: When ovalbumin-liposome conjugates were added to a culture of macrophages, enhanced recognition and processing of ovalbumin by the macrophages were observed by the inclusion of PS in the liposomes. The results correlated well with those regarding macrophage antigen presentation of liposome-coupled ovalbumin. Furthermore, in vivo immunization in mice with ovalbumin-liposome conjugates made with PS-liposomes induced a significantly higher level of anti-ovalbumin IgG antibody production than was induced by ovalbumin-liposome conjugates made with PC-liposomes. IgE-selective unresponsiveness was induced by ovalbumin-liposome conjugates regardless of the lipid components of liposomes. CONCLUSIONS: These results suggest that the inclusion of PS in liposomes enhances recognition and processing of surface-coupled liposomal antigen by macrophages, and increases liposome immune adjuvant activity.

Adjuvants, Immunologic↗
PubMed1977

The passage of thiamine across the rat placenta and its uptake by the fetal organs. I. The transport of thiamine across the placenta.

It is well known that thiamine is highly soluble in water. However, if chloroplatinic acid (H2PtCl6) is used during fixation, an insoluble, electron-dense thiamine-PtCl6 precipitate is formed. Using this method we performed electron microscope autoradiography of the placental labyrinth of rats in their 15th day of pregnancy after injection into the maternal bloodstream of 3H-thiamine, and we also measured the radioactivity of the tissues, in order to study the transport of the thiamine across the placenta. Both developed silver grains and radioactivity were found in the largest amounts 30 min after injection; the amounts of both declined after 2 hrs and declined further after 5 hrs. The majority of the developed silver grains were localized in the smooth-surfaced endoplasmic reticulum, which is generally thought to be the vehicle for the transport of materials in the cell, while in the mitochondria, Golgi apparatus, etc. the grains were few. Considering the substantial depletion of the amounts of both sivler grains and radioactivity after the relatively short time of 5 hrs, we conclude that the greater portion of the thiamine passes quickly across the placenta to the fetus, where it is used in the metabolism of the fetal organs, and that only a small part of the thiamine is retained in the placenta for its own metabolism.

Animals↗
PubMed1991

Dose-dependent increase in 2,5-hexanedione in the urine of workers exposed to n-hexane.

The concentrations of 2,5-hexanedione (2,5-HD), an n-hexane metabolite, and 2-acetylfuran (2-AF) were measured in urine samples from 123 workers who had predominantly been exposed to n-hexane vapor and 53 workers who had experienced no exposure to solvents. The time-weighted average intensity of exposure to n-hexane vapor was determined by a diffusive sampling method. For biological monitoring of exposure, urine samples were collected late in the afternoon during the second half of a working week and were analyzed in the presence and absence of acid hydrolysis (at pH less than 0.5) for 2,5-HD and 2-AF by gas chromatography on a nonpolar capillary DB-1 column. The urinary 2,5-HD concentration increased as a linear function of the intensity of exposure to n-hexane, showing a correlation coefficient of 0.64-0.77 after acid hydrolysis and that of 0.73-0.83 in the absence of hydrolysis, depending on the correction for urinary density (P less than 0.01 in all cases, with no improvement in the coefficient occurring after the corrections). In contrast, 2-AF levels were independent of n-hexane exposure. The geometric mean 2,5-HD concentration in urine samples from 53 nonexposed men was 0.26 mg/l as observed (i.e., with no correction), 0.19 mg/l after correction for a urinary specific gravity of 1.016, and 0.23 mg/g creatinine after correction for creatinine concentration, and the geometric standard deviation was approximately 2.

Chromatography, Gas↗
PubMed2005

Cardiovascular complications caused by advanced secondary hyperparathyroidism in chronic dialysis patients; special focus on dilated cardiomyopathy.

BACKGROUND: The frequency and prognosis of dilated cardiomyopathy (DCM) caused by secondary hyperparathyroidism (2 degrees HPT) is not known. The purpose of this study was to determine the morbidity of DCM caused by 2 degrees HPT and the efficacy of parathyroidectomy (PTx) in chronic dialysis patients with advanced 2 degrees HPT was analyzed prospectively. METHODS: Between November 2000 and January 2003, 237 dialysis patients who underwent total PTx with forearm autograft at our department were enrolled in this study. Cardiac complications that existed before PTx were examined. Ten patients (4%) had DCM without valvular disease (VD) or ischemic heart disease (IHD). In these 10 patients with DCM before operation, we estimated left ventricular (LV) function at 6 months after PTx, according to echocardiography findings and clinical symptoms. RESULTS: Six months after PTx, left ventricular ejection fraction (LVEF) in these 10 patients was significantly improved, from 31.0 +/- 9.8% before PTx, to 56.8 +/- 13.5% (P = 0.0003), and left ventricular end-diastolic dimension (LVDd) was reduced, from 59.8 +/- 9.7 mm to 46.3 +/- 7.0 mm (P = 0.0014). The symptoms due to DCM and the fall of blood pressure that had occurred during dialysis were clearly improved after PTx. CONCLUSIONS: Advanced 2 degrees HPT can influence LV function, and in patients who suffered from DCM, LV function was dramatically improved by PTx. PTx should be performed immediately in patients with DCM caused by 2 degrees HPT.

Aged↗
PubMed2002

Transrectal high-intensity focused ultrasound for treatment of patients with stage T1b-2n0m0 localized prostate cancer: a preliminary report.

OBJECTIVES: To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue. METHODS: We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed. RESULTS: A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention. CONCLUSIONS: Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.

Aged↗
PubMed2005

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice.

The aquaporin-7 (AQP7) water channel is known as a member of the aquaglyceroporins, which facilitate the transport of glycerol as well as water. Although AQP7 is abundantly expressed on the apical membrane of the proximal straight tubules in the kidney, the physiological role of AQP7 is still unknown. To investigate this, we generated AQP7 knockout mice. The water permeability of the proximal tubule brush-border membrane measured by the stopped-flow method was slightly but significantly reduced in the AQP7 knockout mice compared with that of wild-type mice (AQP7, 18.0 +/- 0.4 x 10(-3) cm/s vs. wild-type, 20.0 +/- 0.3 x 10(-3) cm/s). Although AQP7 solo-knockout mice did not exhibit a urinary concentrating defect, AQP1/AQP7 double-knockout mice had a reduction in urinary concentrating ability compared with AQP1 solo-knockout mice, suggesting that the amount of water reabsorbed through AQP7 in the proximal straight tubules is physiologically substantial. On the other hand, AQP7 knockout mice showed marked glyceroluria (AQP7, 1.7 +/- 0.34 mg/ml vs. wild-type, 0.005 +/- 0.002 mg/ml). This identified a novel glycerol reabsorption pathway in the proximal straight tubules. In two mouse models of proximal straight tubule injury, the cisplatin-induced acute renal failure (ARF) model and the ischemic ARF model, an increase in urine glycerol was observed (pretreatment, 0.007 +/- 0.005 mg/ml; cisplatin, 0.063 +/- 0.043 mg/ml; ischemia, 0.076 +/- 0.02 mg/ml), suggesting that urine glycerol could be used as a new biomarker for detecting proximal straight tubule injury.

Animals↗
PubMed2004

B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice.

BACKGROUND: Several lines of evidence indicate that T-cell responses influence the progression of atherosclerotic disease. Interferon-gamma (IFN-gamma)-producing T cells specific for lesional antigens, including oxidized LDLs and heat shock protein 60 (HSP60), may promote lesion development as well as plaque instability. B7-1 and B7-2 are closely related molecules expressed on antigen-presenting cells that provide costimulatory signals for T-cell activation. This study tested the hypothesis that the ability of T cells to influence atherosclerosis depends on B7-1/B7-2 costimulation. METHODS AND RESULTS: B7-1/B7-2/LDL receptor (LDLR)-deficient mice and LDLR-deficient control mice were fed a 1.25% cholesterol or control diet for 8 and 20 weeks. Total serum cholesterol levels and extent and phenotype of atherosclerosis were analyzed. Splenic and lymph node CD4+ T cells from the animals were cultured with mouse recombinant HSP60 or media and antigen-presenting cells and analyzed for IFN-gamma and interleukin-4 production. The absence of B7-1 and B7-2 significantly reduced early cholesterol diet-induced atherosclerotic lesion development in LDLR-deficient mice compared with B7-1/B7-2-expressing control mice. Furthermore, CD4+ T cells from the cholesterol-fed B7-deficient mice secreted a significantly lower amount of IFN-gamma in response to mouse HSP60 in vitro than did T cells from B7-expressing control mice. CONCLUSIONS: The data show that B7-1 and B7-2 regulated the development of atherosclerotic lesions and the priming of lesional antigen-specific T cells. This study highlights the B7-CD28 pathway as a potentially important target for immunomodulation of atherosclerosis.

Animals↗
PubMedDate not supplied

Differentiation and angiogenesis of central nervous system stem cells implanted with mesenchyme into ischemic rat brain.

After cerebral infarction, necrosis in neural tissues is not usually repaired or reconstructed by the injured brain. We therefore examined the effects on postinfarction repair of implanting central nervous system (CNS) stem cells together with mesenchyme, because CNS stem cells can be expected to adapt and survive in the adult brain. Cerebral infarction was induced by the Koizumi-Longa method, using the adult male spontaneous hypertensive rat model. Reperfusion was performed an hour after middle cerebral artery occlusion. The rat mesencephalic neural plate at the early somite stage (embryonic day 10.5) together with the adjacent ventral mesenchymal tissues was dissected out under the microscope and immediately implanted into the ischemic rat striatum. One month later, the cognitive function was evaluated by the Morris water maze method. Histologic and immunohistochemical examinations of the graft were made with hematoxylin-eosin (H&E), neurofilament-200, and tyrosine hydroxylase (TH) stains. In the water maze study, mean latency times required to reach an escape platform in the implanted animals with surviving grafts were found to be shorter than in those without grafts, but longer than in normal animals. In the spatial probe trial, the number of animals seen to cross the area in the pool where the platform had been located was greater in the implanted rats with surviving grafts than in other groups. Multiple vascularization in the grafted area was observed histologically in H&E-stained tissues, and neurofilament-200-positive cells were recognized in the graft. TH staining revealed within the graft many immunoreactive neuron-like cell bodies with long dendrites. It was suggested that grafted CNS stem cells with mesenchyme may survive and differentiate into mature CNS tissue within the adult ischemic rat brain, constructing vessels in and around the grafts, and may therefore have the potential to be effective in the recovery of the cognitive function of the rat model.

Age Factors↗
PubMed2004

Assessment of bovine X- and Y-bearing spermatozoa in fractions by discontinuous percoll gradients with rapid fluorescence in situ hybridization.

This study was designed to apply the method of discontinuous Percoll gradients for sex preselection in bovine semen by using a current developed molecular technique, fluorescence in situ hybridization (FISH). In addition, we attempted to amplify the level of enrichment of X- or Y-bearing spermatozoa by treating for activating sperm motility performance with 10 mM caffeine. Bovine spermatozoa were fractionated on Percoll gradients into two major subpopulations of motile spermatozoa (bottom fraction) and weak motile spermatozoa (top fraction). The percentage of Y-bearing spermatozoa in the top fraction (52.9%) slightly exceeded and that in the bottom fraction (44.3%) decreased significantly (P<0.001) compared with the theoretical ratio (50:50). Washing sperm with BO medium affected a deviation between the two sex populations, whereas semen activated with caffeine showed no difference in the percentage of X- and Y-bearing spermatozoa in both fractions compared with the theoretical ratio (50:50). These results show that the proportion of X- and Y-bearing bovine spermatozoa can deviate after discontinuous Percoll gradients, although the proportion of X- and Y-bearing bovine spermatozoa was affected by sperm motility of the sample applied.

Animals↗