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71.
Summary In vitro studies were carried out to induce viral transformation of vascular smooth muscle cells. Cultured rabbit arterial smooth muscle cells were infected with simian virus 40 (SV 40), and transformed cultures were produced that exhibit altered morphology, increased growth rate and plating efficiency, growth on semi-solid substrate, and chromosomal abnormalities. Nuclear SV 40 T-antigen was detected in all cells of these cultures. Muscle-specific actin was identified by a specific monoclonal antibody suggesting retention of smooth muscle cell characteristics by the transformed cells. Significant cytoplasmic lipid accumulation occurred in transformed cells incubated with -very low density lipoprotein, as revealed both by chemical analyses and Nile Red lipid staining of the cultures. The transformed smooth muscle cells grow permanently in cell culture. Our investigations show that arterial smooth muscle cells transformed with SV 40 virus exhibit altered phenotypic properties distinct from that of normal arterial smooth muscle cells. 相似文献
72.
Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure 总被引:9,自引:0,他引:9
Yancy CW Fowler MB Colucci WS Gilbert EM Bristow MR Cohn JN Lukas MA Young ST Packer M;U.S. Carvedilol Heart Failure Study Group 《The New England journal of medicine》2001,344(18):1358-1365
BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta-blockers may be smaller in black patients than in patients of other races, but it is unknown whether race influences the response to carvedilol in patients with chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials Program, 217 black and 877 nonblack patients (in New York Heart Association class II, III, or IV and with a left ventricular ejection fraction of no more than 0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25 to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and nonblack patients. RESULTS: As compared with placebo, carvedilol lowered the risk of death from any cause or hospitalization for any reason by 48 percent in black patients and by 30 percent in nonblack patients. Carvedilol reduced the risk of worsening heart failure (heart failure leading to death, hospitalization, or a sustained increase in medication) by 54 percent in black patients and by 51 percent in nonblack patients. The ratios of the relative risks associated with carvedilol for these two outcome variables in black as compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42 to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively. Carvedilol also improved functional class, ejection fraction, and the patients' and physicians' global assessments in both the black patients and the nonblack patients. For all these measures of outcome and clinical status, carvedilol was superior to placebo within each racial cohort (P<0.05 in all analyses), and there was no significant interaction between race and treatment (P> 0.05 in all analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure. 相似文献
73.
D. J. Anderson L. Olaison J. R. McDonald J. M. Miro B. Hoen C. Selton-Suty T. Doco-Lecompte E. Abrutyn G. Habib S. Eykyn P. A. Pappas V. G. Fowler D. J. Sexton M. Almela G. R. Corey C. H. Cabell 《European journal of clinical microbiology & infectious diseases》2005,24(10):665-670
Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients
with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to
determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of
patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients
with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20%
vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar
in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but
mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with
enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation
compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality
rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics,
mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers
in this study. 相似文献
74.
An investigation into the relationship between salivary cortisol,stress, anxiety and depression 总被引:3,自引:0,他引:3
Vedhara K Miles J Bennett P Plummer S Tallon D Brooks E Gale L Munnoch K Schreiber-Kounine C Fowler C Lightman S Sammon A Rayter Z Farndon J 《Biological psychology》2003,62(2):89-96
This study examined the relationship between indices of self-reported emotional distress and absolute versus change in cortisol levels. Fifty-four women attending a diagnostic breast clinic completed scales measuring stress, anxiety and depression and provided five saliva samples over the course of a single day for the measurement of cortisol. No significant relationships were evident between absolute cortisol levels and the distress measures. Analysis of the change in cortisol levels revealed a non-linear interaction effect between stress and anxiety and time of day. There was a non-linear relation between time of day and cortisol levels, but the extent of the non-linearity was dependent upon levels of stress and anxiety, not depression. A relationship was apparent between indices of distress and change in cortisol levels, but not absolute levels of the hormone. 相似文献
75.
76.
Overexpression of aromatase leads to development of testicular leydig cell tumors : an in vivo model for hormone-mediated TesticularCancer 下载免费PDF全文
Fowler KA Gill K Kirma N Dillehay DL Tekmal RR 《The American journal of pathology》2000,156(1):347-353
Despite recent advances in diagnosis and treatment of testicular cancer, its causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation. Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis. Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were infertile and/or had larger than normal testicles. Gross pathology and histological analysis showed the mice to have Leydig cell tumors, unilaterally or bilaterally. Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor were also very high in testicular tissue of transgenic mice compared to nontransgenic mice. Consistent with increased estrogenic activity in the testicular tissue, we also saw an increase in the levels of genes involved in cell cycle that are regulated by the estrogen. To obtain a better understanding of the biological significance of testicular tumorigenesis, a reliable animal model is necessary to clarify the mechanisms and correlations associated with human cancers. Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors). This predictable and useful model is a potential tool for the study of testicular tumorigenesis, hormonal carcinogenesis, synergistic action of other carcinogens on hormone-induced tumors, and tumor dependency on endocrine factors. 相似文献
77.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
78.
Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2 总被引:2,自引:0,他引:2
Campbell KA; Studer EJ; Kilmon MA; Lees A; Finkelman F; Conrad DH 《International immunology》1997,9(8):1131-1140
A novel system to study the effects of co-cross-linking CD23/FceRII and sIg
on murine B lymphocytes utilizes a highly multivalent form of anti- Ig
prepared by covalently linking anti-Ig antibodies to a DNP-dextran
backbone. CD23-sIg co-cross-linking is accomplished by the addition of
DNP-specific monoclonal IgE. Previous studies demonstrated that co-
cross-linking CD23 and sIg significantly inhibited mouse B cell
proliferation, especially at high doses of the multivalent anti-Ig.
Interestingly, examination of early activation signals reveals no
difference in B cells subjected to co-cross-linking conditions as compared
to B cells activated with anti-Ig alone. Total cellular protein tyrosine
phosphorylation levels are unchanged by co-cross- linking. Analysis of B
cell mRNA reveals that co-cross-linking the receptors does not alter the
expression levels of ornithine decarboxylase 8 h after stimulation as
compared to the controls. In contrast, levels of the proto-oncogene c-myc
were significantly elevated 1 h after inducing B cell activation under
co-cross-linking conditions. However, it remains unclear whether this
aberrant c-myc regulation plays any role in inducing apoptosis. In
addition, on day 3 after stimulation, the co-cross-linking of CD23 and sIg
resulted in the formation of apoptotic B cells, determined by both
photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei.
B cells obtained from bcl-2 transgenic mice proliferated as well as
controls, and failed to undergo apoptosis when CD23 and sIg were
co-cross-linked on their surface. These studies indicate that
co-cross-linking of CD23 with B cell sIg inhibits B cell proliferation by a
mechanism that is distinct from that seen by co-cross-linking of the Fc
gamma RII and sIg. In addition, these results suggest a means by which
antigen- specific IgE can down-regulate additional B cell activation and
IgE synthesis.
相似文献
79.
A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy 总被引:6,自引:1,他引:6
Fowler PA; Evans LW; Groome NP; Templeton A; Knight PG 《Human reproduction (Oxford, England)》1998,13(12):3530-3536
Maternal serum concentrations of inhibin-A, inhibin-B, activin-A,
activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids
and gonadotrophins were measured longitudinally in six normal singleton
pregnancies. Maternal venous blood was collected randomly during a
spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11,
16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the
early puerperium. Steroid and gonadotrophin profiles conformed to previous
reports. While at week 5 of gestation inhibin-A, activin-A and follistatin
concentrations were similar to those at the follicular phase, all three
increased progressively (P < 0.001) to maximal concentrations in week
36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately
22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/-
418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum
in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174
pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was
undetectable (<12 pg/ml) between week 5-16 of gestation but increased
slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was
undetectable throughout pregnancy. Post-partum concentrations of inhibin-A
(41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml),
pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were
substantially lower than at week 36 of gestation. The activin-A:follistatin
ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more
free activin-A is available in the maternal circulation during late
pregnancy.
相似文献
80.
Potassium secretion by distal tubule after potassium adaptation 总被引:14,自引:0,他引:14