Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin

Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a >80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step of platelet production.     

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.     

Increased expression of CD80, CD86 and CD70 on T cells from HIV-infected individuals upon activation in vitro: regulation by CD4+ T cells

T cells express CD28 and CD27 which transduce co-stimulatory signals after interaction with their ligands on antigen-presenting cells (APC). These ligands, CD80, CD86 and CD70, are also expressed to some extent on activated T cells. Here, we show that in human immunodeficiency virus (HIV)-infected individuals, CD28 and CD27 expression is decreased on CD8+ T cells. On the other hand, T cell stimulation in vitro induced high CD80, CD86 and CD70 expression on T cells from HIV-infected individuals. It appeared that an inverted CD4:CD8 T cell ratio could explain this enhanced expression of co-stimulatory ligands. Indeed, high expression levels of CD80, CD86 and CD70 were found on activated CD8+ T cells from HIV- individuals cultured in the absence of CD4+ T cells. Addition of CD4+ T cells prevented this up-regulation. However, in HIV-infected individuals, addition of excess autologous or healthy control CD4+ T cells did not completely counteract up-regulation of co-stimulatory ligand expression on CD8+ T cells. Thus, to some extent, CD8+ T cells in HIV-infected individuals appeared to be refractory to CD4+ T cell-mediated regulation of ligand expression in vitro. Activated T cells from HIV-infected individuals and activated CD8+ T cells from healthy controls were able to act as accessory cells in CD3-induced T cell proliferation, which was dependent on cell-cell contact. Thus, we showed that T cells from HIV-infected individuals express enhanced levels of co-stimulatory ligands upon activation, which provides them with accessory cell properties. Enhanced stimulatory potential of these nonprofessional APC may contribute to persistently high levels of immune activation in HIV infection related to disease progression.     

The postpubertal change in the playful defense of male rats depends upon neonatal exposure to gonadal hormones

Only 19 cases of metastases at the cannula insertion site after laparoscopy for gynecological malignancy have been reported in the literature. One case has been diagnosed with cervical squamous cell carcinoma, whereas the others have been diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel case of laparoscopy-site abdominal wall metastasis from endometrial cancer after laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient exhibited metastases of an abdominal wall trocar site and a perineal site after undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node sampling as well as LA para-aortic lymph node sampling for treating endometrial carcinoma, surgical staging IIIC, G3. The interval between the surgical extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6 months, suggesting that overmanipulation of the diseased organ during laparoscopic surgery may have resulted in tumor spillage, intraperitoneal dissemination, and wound contamination. Although this procedure has been proven beneficial to patients with benign disease or early-stage gynecologic malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious to eradicate advanced gynecological malignancy.     

Promotion of healthy lifestyle: knowledge and attitudes of primary care physicians

Preretinal neovascularization and chronic retinal oedema are the two major sight-threatening complications that can occur during diabetic retinopathy. Ocular neovascularization is strongly associated with retinal ischaemia, and growth factors have been implicated in its pathogenesis. The ischaemic retina is assumed to secrete growth factors that stimulate residual vessels to proliferate. Interest has focused on basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta) and more recently vascular endothelial cell growth factor (VEGF). Histologic studies have demonstrated the presence of growth factor proteins and receptors and/or their mRNA, mainly VEGF, PDGF, and bFGF, in preretinal membranes of patients with proliferative diabetic retinopathy. Elevated intravitreal levels of IGF-1 and VEGF correlating with neovascular activity have been found in some patients. However, a direct causal relationship between ischaemia, growth factors and neovascularization has not been clearly demonstrated despite considerable research work. To date, the growth factor correlating most closely with neovascularization is VEGF. As many growth factors seem to be produced during the neovascular process, their specific inhibition probably will have limited effects. Laser photocoagulation of the retina has proved beneficial for regression of new vessels, probably through destruction of the ischaemic retina producing neovascular growth factors, and is currently the only treatment for proliferative diabetic retinopathy. Inhibition of IGF-1 by somatostatin analogs has produced unsatisfactory results. Other vascular inhibitors are currently being studied.     

Financing nurse anesthesia education

Health care spending in the United States outpaces all other nations or 14% of the gross domestic product. Although the escalating increases in health care costs which have characterized the industry over the past quarter century have begun to slow down, if changes in the current health care policy are not implemented, spending is expected to increase at a rate of 11.5% during each of the next 5 years. Health care spending will reach $1.1 trillion or 15% of the gross domestic product in the near future. Both hospitals and universities are facing mounting pressures to reduce their costs and improve their services. In this environment, it becomes increasingly important for directors of nurse anesthesia programs to financially justify their existence. This discussion begins with a brief overview of nurse anesthesia education in the United States. The value of and need for nurse anesthetists in the US health care system is addressed. Advantages and disadvantages of hospital versus university-based programs are highlighted and funding sources identified. Future needs and challenges in nurse anesthesia education conclude this discussion.     

Effects of quinine on the mechanical frequency response of the cupula in the fish lateral line

Quinine induces changes in the motion of the cupula in the lateral line canal of the African knife-fish in response to sinusoidal water movements. Two different phases in the action of quinine on the cupular frequency response can be discerned. In the first phase the best frequency, i.e., the frequency at which the cupular vibratory displacement is maximal in response to constant-amplitude sinusoidal canal fluid displacement, shifts toward higher frequencies. During this phase, lasting about 70-100 min, the best frequency increases by a factor between 1.3 and 1.5. In the second phase, during roughly the following 90 min, the best frequency decreases gradually to a value 0.3-0.5 times that observed before the application of quinine.