Biomedical subjects

B Y Wang

Publications and source records attributed to B Y Wang.

At least 19 recordsLinked to original sources

PubMed2006

Immunohistochemical detection of GLUT1, p63 and phosphorylated histone H1 in head and neck squamous intraepithelial neoplasia: evidence for aberrations in hypoxia-related, cell cycle- and stem-cell-regulatory pathways.

AIM: Most epithelial malignancies are characterized by multistep progression from preinvasive/intraepithelial neoplasia to invasive malignancy. Detection and grading of early squamous intraepithelial neoplasia may at times be problematic. The aim of this study was to examine the ability of immunomarkers GLUT1, phospho-histone H1 and p63 to detect such early lesions. METHODS: Sections of formalin-fixed paraffin-embedded tissue from 27 cases of squamous intraepithelial neoplasia, 26 associated with invasive carcinoma, were immunostained with anti-p63 (4A4; Santa Cruz), anti-GLUT1 (Chemicon) and anti-phospho-histone H1 (monoclonal 12D11) and compared with normal, hyperplastic and immature squamous metaplastic epithelium. RESULTS: Normal epithelium displayed phospho-histone H1 in scattered parabasal cells; p63 in the basal one-quarter to one-half of epithelium; and GLUT1 negativity or weak/equivocal mid-epithelial GLUT1+ foci. In hyperplasia phospho-histone H1+ cells were also limited to the parabasal layer; p63 positivity was essentially identical to that in normal epithelium; GLUT1 characteristically stained basal cells in rete-like areas. p63 staining in squamous intraepithelial neoplasia (grade 1) was indistinguishable from normal epithelial staining; in contrast, squamous intraepithelial neoplasia (grade 3) was readily apparent, with up to full-thickness p63 positivity. Squamous intraepithelial neoplasia (grade 1) was readily distinguishable from normal epithelium with both phospho-histone H1 and GLUT1 immunostaining; both markers were detected in cell layers above the parabasal layer. With both, progressively higher cell layers stained in proportion to the severity of the intraepithelial neoplasia, up to full thickness positivity in grade 3 squamous intraepithelial neoplasia. Squamous metaplasia and grade 3 squamous intraepithelial neoplasia were not distinguishable with p63 (both showed full-thickness staining) but were readily distinguishable with GLUT1 and phospho-histone H1 stains. GLUT1 appeared to be the most sensitive marker for all grades of intraepithelial neoplasia. CONCLUSION: Altered expression of all three markers was a common finding in squamous intraepithelial neoplasia, hence, dysregulation of cell cycle-promoting cyclin-dependent kinases (phospho-histone H1), altered stem cell regulatory pathways (p63) and enhancement of hypoxia-sensing pathways (GLUT1) are all early alterations in the progression of squamous malignancy of head and neck origin. A panel of all three may be a useful means of detecting squamous intraepithelial neoplasia.

Biomarkers, Tumor↗

PubMed2002

Genetic exchange between Treponema denticola and Streptococcus gordonii in biofilms.

Some gram-positive oral bacteria such as Streptococcus gordonii are naturally transformable. We investigated the possibility of genetic exchange among oral bacteria using an erythromycin-resistant (Erm(r)) shuttle plasmid, pKMR4PE, as an indicator. S. gordonii Challis cells were co-cultivated with purified pKMR4PE or with Trepomena denticola harboring pKMR4PE either in broth or in artificial biofilms. Transformation of S. gordonii occurred both in broth and in biofilms with pKMR4PE or T. denticola harboring pKMR4PE as donor sources. These results provide direct experimental evidence that gene transfer can occur from T. denticola to S. gordonii.

Anti-Bacterial Agents↗

PubMed2001

Renal cell carcinoma with intravascular lymphomatosis: a case report of unusual collision tumors with review of the literature.

We report the case of a 77-year-old white woman who presented with a left breast mass, lethargy, and weight loss. Pelvic computed tomographic scan revealed a 9.5-cm mass in the right kidney. Surgical pathology demonstrated a diffuse large B-cell lymphoma of the subcutaneous tissue of the breast and renal cell carcinoma with concurrent extensive intravascular lymphomatosis. Systemic dissemination of malignant lymphoma to a concurrent visceral primary neoplasm is rare. To the best of our knowledge, this is the first case illustrating a renal cell carcinoma collision with intravascular lymphomatosis.

Aged↗

PubMed2001

Improving effects of SSF on memory deficits and pathological changes of neural and immunological systems in senescent mice.

AIM: To study the effects of SSF, an effective part isolated from Scutellaria baicalensis George, on memory impairments and the pathological changes of neural and immunological systems in senescent mice induced by chronic galactose. METHODS: Senescent performance in mice was induced by consecutive administration of D-galactose (120 mg/kg, ip) for 47 d. The behavioral tests of mice used water maze task. The neural and immunological changes were assessed by alterations of cerebral cortex morphology and immune tissue index. The improving effects of SSF (50, 100, and 200 mg/kg, ig, 47 d) on above changes in the senescent mice were detected. Piracetam (PIR) was as reference drug. RESULTS: D-Galactose (120 mg/kg, ip, 47 d) resulted in an increase in the latencies to find the terminal platform and the number of errors entering non-exits in water maze, neuropathological changes and immune tissue index (spleen index) deducted in mice as compared with saline treated group. Both PIR (200 mg/kg, ig, 47 d) and SSF (50, 100, and 200 mg/kg, ig, 47 d) could significantly reverse the increased latencies and number of errors and improve the pathological alterations of neural and immunological systems. CONCLUSION: SSF could ameliorate the cognitive deficits and pathological alterations of neuron and immune systems in senescent mice induced by chronic galactose.

Aging↗

PubMed2000

Successful prevention of autoimmune disease by transplantation of adequate number of fully allogeneic hematopoietic stem cells.

BACKGROUND: We have previously shown successful engraftment of allogeneic hematopoietic stem cells (HSCs) when transplanted across the major histocompatibility antigen barriers if transplanted along with a preparation of facilitator cells (osteoblasts). We have investigated whether or not fully allogeneic HSCs from healthy mouse donors prevent the development of autoimmunities in the autoimmune-prone W/B F1 mice. METHODS: W/B F1 is a strain of mice that spontaneously develop autoimmunities, a coronary vascular disease, thrombocytopenia, and systemic lupus-like syndrome. The 6- to 8-week-old (before the onset of the disease) W/B F1 mice have been transplanted with either a preparation of HSCs alone, or along with facilitator cells from MHC-incompatible autoimmune-resistant BALB/c mice, then followed to determine longterm survival and whether or not they developed signs of the autoimmune disease. RESULTS: The number of the transplanted HSCs acts as the determining factor in achieving successful and durable engraftment. Survival of the W/B F1 mice significantly improved by transplantation of increasing numbers of HSCs, either alone or along with facilitator cells. When W/B F1 mice were transplanted with 2-5 million HSCs, more than 1-year survival was 100%, all the transplanted mice were fully engrafted with allogeneic HSCs, and were free of signs of the autoimmune disease. Histological sections of the hearts, lungs, and kidneys of the transplanted mice showed absence of the autoimmune-associated pathology. CONCLUSIONS: We thus report herein the successful prevention of autoimmune disease by transplantation of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.

Animals↗

PubMed2000

Immunohistochemical staining of GLUT1 in benign, hyperplastic, and malignant endometrial epithelia.

BACKGROUND: Aberrant expression of the facilitative glucose transporter, GLUT1, is found in a wide spectrum of epithelial malignancies. The current study describes an immunohistochemical study of GLUT1 expression in benign, hyperplastic, and malignant endometrial epithelia. METHODS: One hundred sixteen formalin fixed, paraffin embedded sections of benign, hyperplastic, and malignant endometrial epithelium were immunostained with rabbit anti-GLUT1 antibody using the streptavidin-biotin method. RESULTS: Proliferative, secretory, and atrophic endometrium were not stained with GLUT1 antiserum. Rare, minute foci of tubal metaplasia stained positively. Simple and complex endometrial hyperplasias were consistently GLUT1 negative. All specimens of atypical hyperplasia had foci that were positive for GLUT1. All endometrial adenocarcinomas were GLUT1 positive. CONCLUSIONS: The results of the current study appear to indicate that 1) aberrant overexpression of GLUT1 is a consistent feature of endometrioid adenocarcinoma; 2) GLUT1 immunostaining may be useful in distinguishing benign hyperplasias from hyperplasias that are associated strongly with malignancy; and 3) some or all cases of atypical hyperplasia may be neoplastic rather than hyperplastic, given the existence of a molecular defect common to this hyperplastic subtype and endometrioid adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Fine-needle aspiration diagnosis of synovial chondromatosis of the tibiofibular joint.

We report a case of synovial chondromatosis of the tibiofibular joint in a 25-year-old woman that was diagnosed by fine-needle aspiration (FNA). The patient presented with pain in the left knee and a mass in the popliteal fossa. Synovial chondromatosis usually presents with joint symptoms and is often associated with intra-articular loose bodies, whereas presentation as a soft tissue mass is unusual and may raise the clinical suspicion of malignant neoplasm. The diagnosis is commonly confirmed by histopathologic examination of biopsy or excision of the specimen. To the best of our knowledge, this is the first case of synovial chondromatosis of a large joint successfully diagnosed by FNA. Two cases of synovial chondromatosis of the temporomandibular joint have been reported in which the diagnosis was suspected on the basis of FNA. In both these cases, the final diagnosis was established by histopathology of the excised specimens.

Adult↗

PubMed1999

Regression of atherosclerosis: role of nitric oxide and apoptosis.

BACKGROUND: We have recently found that administration of L-arginine to hypercholesterolemic rabbits induces regression of preexisting lesions. Others have previously shown that activation of the L-arginine/nitric oxide (NO) synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly, the current study was designed to determine if dietary supplementation of L-arginine induces apoptosis of intimal lesions and if this effect is mediated through the NO synthase pathway. METHODS AND RESULTS: Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on 2.5% L-arginine HCl in the drinking water, and the cholesterol diet was continued for 2 weeks, at which time the aortas were harvested for histological studies. L-Arginine treatment increased the number of apoptotic cells (largely macrophages) in the intimal lesions by 3-fold (11.9+/-3.9 vs 3.9+/-1. 4 apoptotic cells/mm2, P<0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic segments were incubated in cell culture medium for 4 to 24 hours with modulators of the NO synthase pathway. The tissues were then collected for histological studies and the conditioned medium collected for measurement of nitrogen oxides by chemiluminescence. Addition of sodium nitroprusside (10(-5) mol/L) to the medium caused a time-dependent increase in apoptosis of vascular cells (largely macrophages) in the intimal lesion. L-Arginine (10(-3) mol/L) had an identical effect on apoptosis, which was associated with an increase in nitrogen oxides released into the medium. These effects were not mimicked by D-arginine, and they were antagonized by the NO synthase inhibitor L-nitro-arginine (10(-4) mol/L). The effect of L-arginine was not influenced by an antagonist of cGMP-dependent protein kinase, nor was the effect mimicked by the agonist of protein kinase G or 8-BR cGMP. CONCLUSIONS: These results indicate that supplemental L-arginine induces apoptosis of macrophages in intimal lesions by its metabolism to NO, which acts through a cGMP-independent pathway. These studies are consistent with our previous observation that supplementation of dietary arginine induces regression of atheroma in this animal model. These studies provide a rationale for further investigation of the therapeutic potential of manipulating the NO synthase pathway in atherosclerosis.

Animals↗

PubMed1999

Malignant melanomas of the parotid: comparison of survival for patients with metastases from known vs unknown primary tumor sites.

BACKGROUND: Malignant melanoma (MM) rarely affects the parotid, and usually this diagnosis will herald a search for a primary skin neoplasm. Occasionally, no primary tumor is ever found, raising questions regarding prognosis and the issue of primary melanoma of the parotid. OBJECTIVE: To evaluate retrospectively the clinical and histological features of MM involving the parotid in 19 patients. DATA SOURCES: Pathology and hospital files at 3 tertiary care university hospitals. STUDY SELECTION: Patients with MM within the parotid with adequate histopathologic and immunohistochemical documentation, as well as clinical information regarding patient outcome. DATA EXTRACTION: In 6 patients, no extraparotid MM was ever identified. After parotidectomy, 5 patients (including 1 patient who died of other causes) were melanoma free at a mean of 4.2 years (range, 14 months to 7.5 years). Only 1 patient died of disease after 17 months. An extraparotid primary tumor was present in 13 patients, 10 with dermal and 3 with mucosal sites. At follow-up, only 1 of these patients was disease free after 2 years. Nine patients died of melanoma after a mean of 2.6 years (range, 10 months to 5 years); the other 3 had evidence of metastatic disease at a mean of 4.3 years (range, 3-6 years). Nondermal sites of primary tumors were the nasal cavity, sclera, and conjunctiva. DATA SYNTHESIS: Patients with metastatic MM from unknown primary tumors have a longer disease-free survival than those with metastases from known primary disease. CONCLUSIONS: Although rare, MM should be considered in the differential diagnosis of parotid tumors. Unusual mucosal or ocular sites should be considered in the search for possible primary tumor sites to avoid treatment delay. These data support the idea that patients with metastatic MM from unknown primary tumors may follow a more improved course than that of patients with metastases from known primary disease.

Adult↗

PubMed1999

Carcase composition of Taiwan simulated native chickens.

This study investigated the carcase composition of Taiwan simulated native chickens at different stages of growth. The results indicated that the carcases of male chickens exhibited significantly larger protein mass and water mass than those of females during weeks 7 to 20; as was the ash mass during weeks 8 to 20. However, the fat mass of the carcases of female chickens was larger than that of males during weeks 14 to 20. Separate regression equations were derived for the relationship between protein mass, fat mass, ash mass and water mass and both carcase weight and age of both male and female chickens.

Animal Feed↗

PubMed1999

Mortality associated with concurrent strongyloidosis and cytomegalovirus infection in a patient on steroid therapy.

Disseminated strongyloidosis has been recognized with increasing frequency, often in patients who are immunocompromised or have received steroid therapy. In addition, disease due to cytomegalovirus (CMV) is noted in immunodeficient hosts. We report on a 55-year-old Puerto Rican man who received steroid treatment for orpharyngeal pemphigus vulgaris and developed abdominal symptoms with alternating constipation and diarrhea. The clinical work-up did not reveal specific abnormalities, but the patient died of cardiopulmonary failure. At the postmortem examination, the patient had evidence of strongyloidosis and CMV disease. This report reviews both this case and the literature, and discusses the overlapping infections of strongyloidosis and CMV disease in this patient who had received steroid therapy.

Anti-Inflammatory Agents↗

PubMed1998

Interaction of diabetes and hypertension on determinants of endothelial adhesiveness.

Epidemiological studies have established that diabetes mellitus and hypertension are independent risk factors for atherosclerosis. One of the earliest abnormalities seen in atherogenesis is enhanced monocyte adherence to the endothelium. The mechanisms by which diabetes mellitus or hypertension enhances monocyte-endothelial cell interactions are incompletely characterized. It is not known whether there are additive interactions between these risk factors on endothelial adhesiveness for monocytes. Male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were fed a normal or fructose-enriched diet. In some cases, animals were injected with streptozotocin (35 mg/kg body weight) to induce diabetes. After 2 weeks, plasma was drawn for biochemical measurements, and thoracic aortas were harvested, opened longitudinally, and exposed to fluorescently labeled mouse monocytoid cells (WEHI 78/24, 2 x 10(6)/mL) for 30 minutes on a rocking platform. Adherent cells were counted by epifluorescence microscopy. WEHI 78/24 binding to aortic segments from SHR animals was elevated compared with segments from WKYs. Fructose feeding alone had no effect on endothelial adhesiveness. When WKYs were made hyperglycemic by STZ injection, monocyte binding was 160% of the control value. Elevated monocyte binding was also observed in aortas derived from SHR animals injected with STZ, indicating an additive effect of hypertension and hyperglycemia. To determine whether alterations in oxidative state played a role in the endothelial adhesiveness, aortic segments were exposed to lucigenin (250 micromol/L) for measurement of superoxide anion. Aortic segments from SHR elaborated 120% more superoxide anion than did controls. Elevated free-radical production was also observed in aortas from diabetic WKYs. Furthermore, thoracic aortas derived from diabetic SHR animals elaborated more superoxide anion than did any of the other groups (374%, P<0.05). Immunohistochemical staining for monocyte chemotactic protein-1 demonstrated increased expression in aortas isolated from diabetic WKY and SHR compared with control vessels. These studies demonstrate that both diabetes and hypertension lead to increased monocyte adherence to the endothelium. This abnormality is associated with increased vascular superoxide production and monocyte chemotactic protein-1 expression. Furthermore, there appears to be an additive interaction between hyperglycemia and hypertension in their effects on endothelial adhesiveness and its determinants.

Animals↗

PubMed1998

Calorie restriction delays the crescentic glomerulonephritis of SCG/Kj mice.

Reduced dietary calories can delay the onset and diminish the severity of murine autoimmunities of numerous inbred and hybrid mutant strains. We sought to determine whether the precipitous, autoimmune, crescentic glomerulonephritis of recombinant inbred SCG/Kj mice could be abrogated similarly by calorie restriction. Weanling SCG/Kj mice develop hematuria and proteinuria, and 50% die as 16-week-old young adults. In this study, 113 4-week-old SCG/Kj mice were fed either ad libitum a milled chow (Group A, n = 50), or a semipurified diet (Group B, n = 29), or were fed a calorie-restricted semipurified diet (Group C, n = 34), so that mice of Group C consumed approximately 32% fewer calories, but similar amounts of essential dietary constituents as those of Group B. Calorie restriction of Group C provided modest (P = 0.05) or substantial survival advantage (P = 0.001) compared to the ad libitum feeding of Groups B or A, respectively. Progression to severe glomerular pathology was delayed among Group C mice, with more than a 5-week delay to heavy proteinuria (>100 mg/dl), a >4-week delay to hematuria, and a >5-week delay to median mortality, representing a 20% or 25% extension of median life span, compared to ad libitum-fed Group B and A mice, respectively. Mean glomerular histopathology scores were also lower in calorie-restricted mice compared to the ad libitum-fed cohorts (P = 0.001). Titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies developed in weanlings prior to the full imposition of calorie restriction and were not reduced significantly by calorie restriction.

Animals↗

PubMed1998

Prevention of crescentic glomerulonephritis in SCG/Kj mice by bone marrow transplantation.

Transplantation of MHC-compatible, T-cell-depleted, bone marrow cells has successfully treated autoimmunities, immunodeficiencies, malignancies, and developmental deficiencies of the hematopoietic system. Recombinant inbred SCG/Kj mice develop spontaneous crescentic glomerulonephritis, systemic vasculitis, and a lymphoproliferative disorder early in life. To determine whether the precipitous autoimmune disease of SCG/Kj mice could be treated by bone marrow transplantation, 30 SCG/Kj mice were engrafted with T-cell-depleted, bone marrow (TCDM) from allogeneic, MHC-compatible, autoimmune-resistant C3H/He donors, and 30 SCG/Kj mice served as controls and received TCDM from syngeneic, SCG/Kj donors. A significant survival advantage was evident from SCG/Kj mice engrafted with C3H/He TCDM (p < 0.005), and an 89% extension of median survival compared to recipients of SCG/Kj TCDM. Within 28 weeks post-transplantation, 62% of mice engrafted with SCG/Kj TCDM had died with clinical signs of fatal crescentic glomerulonephritis. This result compared with only 10% of mice engrafted with C3H/He TCDM. Mice engrafted with SCG/Kj TCDM developed significantly greater titers of autoantibodies to ss-DNA, ds-DNA, and myeloperoxidase (ANCA) (p < 0.001), had shorter latencies to the development of, and a greater incidence of proteinuria, hematuria, and peripheral lymphadenopathy, and a greater mean grade of glomerular lesion (p < 0.001), than mice engrafted with C3H/He TCDM. These findings indicate that the genetic defect of the SCG/Kj strain of mice resides within the hematopoietic stem cells and provokes the speculation that bone marrow transplantation might be a useful means of treating progressive crescentic glomerulonephritis in humans.

Animals↗

PubMed1998

Osteoblasts promote engraftment of allogeneic hematopoietic stem cells.

Hematopoietic progenitor cells (low density, lineage negative [Lin-], depleted of CD4+, CD8+, B220+, Gr-1+, Mac-1+, CD71+, and Thy1.2+ cells) can engraft lethally irradiated mice when transplanted within, but not across the major histocompatibility (MHC) antigen barrier. We hypothesized that our progenitor cell preparation required "supportive" cells/factors for successful engraftment. Our initial candidate supportive cells, dendritic cells, failed to facilitate engraftment of stem cells across fully allogeneic MHC barriers. Because interaction of stem cells with bone marrow (BM) stromal microenvironment is required for development, maturation, and differentiation of hematopoietic stem cells, and because bone transplants have been found to facilitate BM transplantation (BMT) in some strain combinations, we tested bone progenitor cells, osteoblasts, as facilitators of allogeneic stem cell engraftment. Osteoblasts, purified from donor murine long bones, were cotransplanted with marrow stem cells into fully allogeneic mouse strains. The transplanted mice demonstrated excellent long-term survival, were free of disease, and were entirely engrafted with cells of donor origin. Histologic sections of thymuses and spleens showed full reconstitution of lymphohematopoietic elements. Surprisingly, in contrast to fully allogeneic chimeras reconstituted by allogeneic T lymphocyte-depleted BM, our stem cell chimeras were found to produce an impressive primary antibody response to the cellular antigen, sheep red blood cells. Thus, bone progenitor cells or osteoblasts may represent an essential component of the stromal cell population and facilitate engraftment of marrow stem cells in an allogeneic environment.

Alkaline Phosphatase↗

PubMed1997

Prevention of development of autoimmune disease in BXSB mice by mixed bone marrow transplantation.

Transplantations of fully allogeneic, autoimmune-resistant T-cell-depleted marrow (TCDM) plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice were carried out to investigate the ability of the mixed bone marrow transplantation (BMT) to prevent development of autoimmune disease and, at the same time, to reconstitute fully the immunity functions of heavily irradiated BXSB recipients. Male BXSB mice were engrafted with mixed TCDM from both allogeneic, autoimmune-resistant BALB/c mice and syngeneic, autoimmune-prone BXSB mice. BMT with mixed TCDM from both resistant and susceptible strains of mice (mixed BMT) prolonged the median life span and inhibited development of glomerulonephritis in BXSB mice. BMT with mixed TCDM also prevented the formation of anti-DNA antibodies that is typically observed in male mice of this strain. Moreover, mixed BMT reconstituted primary antibody production in BXSB recipients, so that no annoying immunodeficiencies that are regularly observed in fully allogeneic chimeras were present in the recipient of the mixed TCDM. These findings indicate that transplanting allogeneic, autoimmune-resistant TCDM plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice prevents development of autoimmune disease in this strain of mice. In addition, this dual BMT reconstitutes the immunity functions and avoids the immunodeficiencies that occur regularly in fully allogeneic chimeras after total-body irradiation.

Animals↗

PubMed1997

Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans.

OBJECTIVES: The present study was designed to test the hypothesis that long-term dietary supplementation with the nitric oxide precursor L-arginine would enhance vascular or platelet-derived nitric oxide activity, or both, and thereby inhibit platelet reactivity in hypercholesterolemic humans. BACKGROUND: We have shown that reduced vascular activity of nitric oxide in hypercholesterolemic rabbits can be restored by L-arginine supplementation. The improvement in nitric oxide activity is associated with an inhibition of platelet aggregation ex vivo. This effect is most likely due to increased elaboration of endothelium- or platelet-derived nitric oxide, or both, because the inhibition of platelet reactivity was associated with elevation of intraplatelet cyclic guanosine monophosphate and was reversed by the nitric oxide synthase antagonist N-methyl-arginine. METHODS: In a double-blinded, randomized, placebo-controlled trial, hypercholesterolemic patients were assigned to L-arginine hydrochloride, 8.4 g/day orally, or placebo for 2 weeks. Platelet-rich plasma was obtained for aggregometry induced by collagen (1 to 10 micrograms/ml) at four points: baseline, after 2 weeks of treatment, after a 2-week washout and after a long-term washout of 16 weeks on average. Aggregation was quantified by light transmittance and expressed as a percent transmittance observed with platelet-poor plasma. RESULTS: Compared with normocholesterolemic control subjects, platelets from hypercholesterolemic subjects stimulated with 5 micrograms/ml of collagen showed increased aggregability (68.6% in hypercholesterolemic patients vs. 54.5% in normocholesterolemic control subjects, p < or = 0.02). After 2 weeks of treatment with L-arginine (but not placebo), platelet reactivity was modestly reduced; this effect persisted for 2 weeks after discontinuation of arginine (52.6% in arginine-treated patients vs. 65.1% in normocholesterolemic control subjects, p = 0.07). After 18 weeks (i.e., 16 weeks after discontinuing arginine treatment), the platelets of hypercholesterolemic patients once again became hyperaggregable, and the extent of platelet aggregation was significantly increased compared with the 4-week point (73.6% after vs. 52.6% during arginine treatment, p < 0.01). No significant change in platelet reactivity was seen in placebo-treated hypercholesterolemic patients throughout the study. L-Arginine treatment was well tolerated without side effects. CONCLUSIONS: This double-blinded, placebo-controlled study demonstrates that dietary supplementation with L-arginine can modestly attenuate the increased platelet reactivity seen in hypercholesterolemic patients. The data are consistent with our previous studies in hypercholesterolemic animals, demonstrating that L-arginine restores endogenous nitric oxide activity and inhibits platelet aggregation. Enhancement of endogenous nitric oxide activity is a potential novel therapeutic strategy worthy of further study.

Arginine↗

PubMed1997

Trophoblasts express Fas ligand: a proposed mechanism for immune privilege in placenta and maternal invasion.

Cross-linking of Fas (CD95, APO-1) and Fas ligand (FasL; CD95L) induces apoptosis of Fas-bearing cells. Recent evidence suggests that FasL. expression plays an important role in maintenance of immune privilege in murine testis and eye and in tumour escape from immune rejection in colon cancer, melanoma and hepatocellular carcinoma. Bcl-2 is a membrane protein that suppresses apoptosis in response to a variety of stimuli. In this paper we describe abundant expression of FasL protein and mRNA transcripts within the immune privileged environment of the placenta by immunohistochemistry and reverse transcription in-situ polymerase chain reaction methods. The syncytiotrophoblast layer, the main site of feto-maternal interface, and extravillous trophoblasts, demonstrated consistent immunoreactivity for FasL in term placentae. Co-occurrence of Fas and Bcl-2 were detected with a similar pattern of distribution with FasL. The TUNEL method revealed evidence of apoptosis in the placental tissues. We speculate that abundant presence of FasL in the trophoblast contributes to immune privilege in this unique environment, perhaps by fostering apoptosis of activated Fas-expressing lymphocytes of maternal origin. An apoptotic process mediated by FasL may also play a role in placental invasion during implantation and underscores similarities between the trophoblast and neoplastic cells.

Apoptosis↗