Frequency of recurrent lupus nephritis among ninety-seven renal transplant patients during the cyclosporine era

The catecholamine precursor l-dihydroxyphenylalanine (L-DOPA) is the primary therapeutic intervention for Parkinson's disease. Although short-term exposure (30 min) potentiates dopamine (DA) release by elevating quantal size, longer term exposure to L-DOPA (48 hr) promotes neurite outgrowth from midbrain DA neurons in culture. To characterize long term effects of L-DOPA, we used a pheochromocytoma (PC12) line that extends neurites on exposure to nerve growth factor (NGF). L-DOPA potentiated the outgrowth of processes elicited by NGF. This response did not require conversion of L-DOPA to DA, was not caused by agonist effects at DA receptors, and was not blocked by the tyrosine kinase inhibitor genistein. However, similar results were found after exposure to l-n-acetylcysteine or apomorphine, a DA receptor agonist that produces a quinone metabolite, and seemed to correlate with glutathione synthesis. Long-term process elaboration was blocked by L-buthionine sulfoximine, consistent with mediation by an antioxidant mechanism. L-DOPA potentiation of NGF response was important functionally as seen by increased quantal neurotransmitter release from the L-DOPA/NGF-treated neurite varicosities, which displayed both 2-fold greater quantal size and frequency of quantal release. These results demonstrate potentiation by L-DOPA of morphological and physiological responses to neurotrophic factors as well as synergistic induction of antioxidant pathways. Together with effects on transmitter synthesis, these properties seem to provide a basis for the compound's long term presynaptic potentiation of DA release and therapeutic actions.     

A sero-epidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras

To investigate a possible cause-and-effect relationship between sexually transmitted diseases and cervical cancer, we performed a sero-epidemiological study on the presence of antibodies against a number of sexually transmitted agents (STAs) in patients with cervical cancer and their matched controls. In this study, we used serological techniques to investigate the presence of antibodies to cytomegalovirus, herpes simplex virus type 2, human immunodeficiency virus, Chlamydia trachomatis, Treponema pallidum and human papillomavirus (HPV) early protein E7 in sera from patients with cervical cancer, cervical intra-epithelial neoplasia and individually matched, healthy controls. The presence of antibodies to infectious agents other than HPV appeared not to be associated with risk of cervical neoplasia in either univariate or multivariate analysis. After adjustment for cytology, schooling and presence of HPV DNA in cervical scrapes, there was a significantly higher prevalence of antibodies to HPV-16 E7 protein in sera from patients with cervical cancer (OR = 3.6, 95% CI 1.0-12.9) than in healthy controls. The highest antibody prevalence was found among HPV-16 DNA-positive cervical cancer patients (33%). Our results indicate that in these study groups past infections with the STA considered seems to be of no apparent relevance for cervical carcinogenesis and that the HPV-16 anti-E7 response appears to be associated with cervical cancer.     

Effect of the gasoline additives on PAH emission

PAH emission from the powered engines fueled by a 95 leadfree gasoline (95-LFG), a 92 leadfree gasoline (92-LFG) and a Premium leaded gasoline (PLG) with two gasoline additives (SA and SB) were collected using a PAH sampling system with a particulate interception device. Twenty one PAHs were analyzed primarily by an GC/MS, while eight metal elements were determined mainly by an ICP-AES. This investigation showed that the gasoline additives contain more amounts of carcinogenic PAHs than gasolines do. Blending these additives do raise the PAH content in the gasolines, simultaneously, will emit more amount of PAHs from the tailpipe of engine exhaust. It is suggested that before a gasoline additive is commercialized, an assessment on its PAH emission should be evaluated to make sure that the additive will not emit more PAHs and cause adverse effect on public health.     

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries

PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.     

Quantification of mitral regurgitation by automated cardiac output measurement: experimental and clinical validation

OBJECTIVES: To develop and validate an automated noninvasive method to quantify mitral regurgitation. BACKGROUND: Automated cardiac output measurement (ACM), which integrates digital color Doppler velocities in space and in time, has been validated for the left ventricular (LV) outflow tract but has not been tested for the LV inflow tract or to assess mitral regurgitation (MR). METHODS: First, to validate ACM against a gold standard (ultrasonic flow meter), 8 dogs were studied at 40 different stages of cardiac output (CO). Second, to compare ACM to the LV outflow (ACMa) and inflow (ACMm) tracts, 50 normal volunteers without MR or aortic regurgitation (44+/-5 years, 31 male) were studied. Third, to compare ACM with the standard pulsed Doppler-two-dimensional echocardiographic (PD-2D) method for quantification of MR, 51 patients (61+/-14 years, 30 male) with MR were studied. RESULTS: In the canine studies, CO by ACM (1.32+/-0.3 liter/min, y) and flow meter (1.35+/-0.3 liter/min, x) showed good correlation (r=0.95, y=0.89x+0.11) and agreement (deltaCO(y-x)=0.03+/-0.08 [mean+/-SD] liter/min). In the normal subjects, CO measured by ACMm agreed with CO by ACMa (r=0.90, p < 0.0001, deltaCO=-0.09+/-0.42 liter/min), PD (r=0.87, p < 0.0001, deltaCO=0.12+/-0.49 liter/min) and 2D (r=0.84, p < 0.0001, deltaCO=-0.16+/-0.48 liter/min). In the patients, mitral regurgitant volume (MRV) by ACMm-ACMa agreed with PD-2D (r= 0.88, y=0.88x+6.6, p < 0.0001, deltaMRV=2.68+/-9.7 ml). CONCLUSIONS: We determined that ACM is a feasible new method for quantifying LV outflow and inflow volume to measure MRV and that ACM automatically performs calculations that are equivalent to more time-consuming Doppler and 2D measurements. Additionally, ACM should improve MR quantification in routine clinical practice.     

Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal alpha(2-6)-linked sialic acids

The human JC polyomavirus (JCV) is the etiologic agent of the fatal central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and is the direct result of JCV infection of oligodendrocytes. The initial event in infection of cells by JCV is attachment of the virus to receptors present on the surface of a susceptible cell. Our laboratory has been studying this critical event in the life cycle of JCV, and we have found that JCV binds to a limited number of cell surface receptors on human glial cells that are not shared by the related polyomavirus simian virus 40 (C. K. Liu, A. P. Hope, and W. J. Atwood, J. Neurovirol. 4:49-58, 1998). To further characterize specific JCV receptors on human glial cells, we tested specific neuraminidases, proteases, and phospholipases for the ability to inhibit JCV binding to and infection of glial cells. Several of the enzymes tested were capable of inhibiting virus binding to cells, but only neuraminidase was capable of inhibiting infection. The ability of neuraminidase to inhibit infection correlated with its ability to remove both alpha(2-3)- and alpha(2-6)-linked sialic acids from glial cells. A recombinant neuraminidase that specifically removes the alpha(2-3) linkage of sialic acid had no effect on virus binding or infection. A competition assay between virus and sialic acid-specific lectins that recognize either the alpha(2-3) or the alpha(2-6) linkage revealed that JCV preferentially interacts with alpha(2-6)-linked sialic acids on glial cells. Treatment of glial cells with tunicamycin, but not with benzyl N-acetyl-alpha-D-galactosaminide, inhibited infection by JCV, indicating that the sialylated JCV receptor is an N-linked glycoprotein. As sialic acid containing glycoproteins play a fundamental role in mediating many virus-cell and cell-cell recognition processes, it will be of interest to determine what role these receptors play in the pathogenesis of PML.     

Alternative treatments for a traumatic bone cyst: a longitudinal case report

A patient presented with a large, multilocular, refractory traumatic bone cyst. The radiolucency had increased in dimension since her last recall. Over 11 years, therapy had included needle aspiration biopsies followed by simple curettage and closure, the most common therapy for traumatic bone cysts. However, all treatment had proved unsuccessful for this patient. It was decided to treat the patient with a slightly unique method. After curettage of the lesion, the traumatic bone cyst was packed with a mixture of autogenous blood, harvested autogenous bone chips, and hydroxyapatite.     

Tyr1]-nociceptin and nociceptin have similar naloxone-insensitive erectile activity in the cat

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G-protein-coupled receptor ORL1. The present study was undertaken to investigate responses to intracavernosal injections of the nociceptin analog [Tyr1]-nociceptin and to investigate the effects of naloxone on erectile responses in anesthetized cats to [Tyr1]-nociceptin and to nociceptin. Intracavernosal injections of [Tyr1]-nociceptin and of nociceptin in doses of 0.3-30 nmol elicited dose-related increases in cavernosal pressure, which, at the highest dose studied, were comparable to increases induced by the triple-drug standard (papaverine, phentolamine, and prostaglandin E1), a preparation used in the treatment of erectile dysfunction. Responses to [Tyr1]-nociceptin were rapid in onset and had a time course similar to responses to nociceptin. Metenkephalin increased cavernosal pressure, whereas injections of nociceptin-(2-17), dynorphin A, and beta-endorphin did not alter cavernosal pressure. Erectile responses to nociceptin and to [Tyr1]-nociceptin were not altered after administration of the opioid receptor antagonist naloxone at a time when erectile responses to metenkephalin were attenuated. These data show that [Tyr1]-nociceptin and nociceptin have similar naloxone-insensitive erectile activity in the cat.     

A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi

Polygonum hypoleucum Ohwi (P. hypoleucum Ohwi) has been used as a Chinese medicine for a long time. In the present study, four anthraquinones, emodin, emodin 1-O-beta-D-glucoside (49A), physcion (62A), and physcion 1-O-beta-D-glucoside (50A) were identified from P. hypoleucum Ohwi and their inhibitory effects on various tumor cells proliferation were investigated. On a percentage basis, emodin had the highest suppressing activity on the various tumor cells proliferation. At 10 microg/ml, the percentage inhibition on K562 cells proliferation for emodin, 49A, 62A, and 50A were 97+/-3.4%, 18+7.3%, 24+/-3.6%, and 31+/-8.9%, respectively. However, inhibitory activities of 10 microg/ml of emodin, 49A, 62A, or 50A on Raji cells proliferation were 98+/-5.0%, 25+/-5.0%, 22+/-3.2%, and 28+/-4.3%, respectively. It was also found that the both C1 and C3 positions of emodin were important for antitumor action. The IC50s of emodin, 49A, 62A, and 50A on various tumor cells were also calculated. The IC50 of emodin on K562 cells was significantly lower than on Raji, HeLa, Calu-1, Wish, and Vero cells (1.5+/-0.2 vs. 2.8+/-0.4 microg/ml, P < 0.01 ;1.5+/-0.2 vs. 8.4+/-1.6 microg/ml; 1.5+/-0.2 vs. 8.9+/-1.0 microg/ml; 1.5+/-0.2 vs. 8.7+/-0.5 microg/ml; 1.5/-0.2 vs. 3.5+/-0.12 microg/ml; P < 0.001). The results indicated that K562 and Raji cells were more sensitive to emodin treatment. Cell viability test indicated that inhibitory effect of emodin on various tumor cell lines was not through direct cytotoxicity. It suggested P. hypoleucum Ohwi included a tumor cell growth inhibitor.     

Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate

Death-associated protein kinase (DAP kinase) has been recently identified as a novel Ca2+/calmodulin-dependent protein kinase and as a potential mediator of gamma interferon-induced cell death of Hela cells, which has cytological characteristics of the programmed cell death. In order to elucidate its functional roles in the rat brain where the programmed cell death is an essential mechanism in the organization of postmitotic neurons during development, we cloned a rat homologue of the human DAP kinase from the rat embryonic brain cDNA library. The deduced amino acid sequence was highly conserved between the two species (93.6%). By in situ hybridization histochemistry, the expression of DAP kinase mRNA was observed in the mantle and ventricular zones of the entire neuraxis on embryonic day 15. However, the overall expression in the brain decreased markedly after birth and the expression was maintained at substantial levels in several restricted mature neuronal populations, such as olfactory bulb, hippocampal formation and cerebellar Purkinje and granule cells. Its wide expression during development and its maintained expression in the restricted mature neuronal population suggest that DAP kinase might be involved in some neuronal functions beyond simply executing the developmental neuronal cell death.