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141.
Beckwith  M; Ruscetti  FW; Sing  GK; Urba  WJ; Longo  DL 《Blood》1995,85(9):2461-2470
We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.  相似文献   
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OBJECTIVES--Vietnamese immigration to the U.S. since the conclusion of the Vietnam war has been substantial and in Orange County, CA, Vietnamese Americans comprise 3% of the population (the largest community in the US). Our objective was to collect data on the HIV/AIDS knowledge, attitudes and self-reported high risk behaviours within this community. METHODS--A survey instrument was administered anonymously in Vietnamese to 532 respondents in their homes. Individuals from three population strata were randomly sampled: men 18 to 35 years old (N = 193); men 36 to 45 years old (N = 137); and women 18 to 35 years old (N = 202). Data were gathered on: (1) degree of acculturation; (2) knowledge and attitudes towards HIV/AIDS; and (3) self-reported sexual and other high risk practices. RESULTS--Survey data indicated that 38% of respondents were very worried about themselves and 83% were worried about a family member getting AIDS. Knowledge about actual modes of HIV transmission was generally accurate, but a substantial minority still believed that HIV can be transmitted through casual contact, and 68% from needles used in hospitals. Women demonstrated less accurate knowledge than men on five key items. Quarantine of the HIV infected was agreed to by 45%. Twenty-nine percent did not believe that the epidemic would affect them personally, and 49% stated that they did not have enough information about AIDS to protect themselves. Regarding sexual practices, 31% reported never having had sex. Of the others, 8% had two or more sexual partners in the prior 12 months. No same sex behaviour was reported. Six percent of men had visited a female prostitute; of these, 24% had visited 2 or more in the prior 12 months; half of encounters in this time period were outside the US. Substantial percentages of sexually active, unmarried respondents indicated that they never use (17-40%) or only sometimes use (10-32%) condoms. Less than 1% had used injection drugs. CONCLUSIONS--Education should be targeted at the Vietnamese community of southern California to improve knowledge that HIV cannot be contracted through casual contact, to convey information about methods for self-protection, and to reduce high risk sexual practices such as unprotected sex, sex with multiple partners and sex with prostitutes.  相似文献   
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Nonsuppurative peripheral thrombophlebitis is a frequently recognized source of sepsis. Eleven patients cared for on general medical and surgical services had Gram-negative bacillary sepsis on this basis. Ten had isolation of organisms of the Klebsiella-Enterobacter group from the involved peripheral vein. All failed to respond to organism-sensitive antibiotics until the involved vein was excised. After local vein excision, all patients were afebrile within 48 hours and recovered. In seven of the 11 patients, the septic phlebitis source was associated with a standard intravenous needle, and none had cutdown procedures. It is strongly emphasized that this condition is a source of life-threatening sepsis that can be treated by vein excision at the bedside. The treatment in our patients resulted in no morbidity. A high index of suspicion is necessary to diagnose this occult source of sepsis because of the minimal local physical signs.  相似文献   
148.
Monitoring human tumor response to therapy by means of P-31 MR spectroscopy   总被引:1,自引:0,他引:1  
Tumors in 23 patients were studied by means of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy. In five patients, the response to chemotherapy and radiation therapy was monitored in a long-term follow-up study. In one patient, the P-31 MR spectra were recorded during the infusion of chemotherapeutic drugs. In comparison with healthy muscle tissue of patients, the tumors showed elevated inorganic phosphate, phosphomonoester, and phosphodiester peaks and reduced creatine phosphate peaks, whereas the nucleoside 5'-triphosphate levels remained nearly unchanged. Tumor treatment resulted in changes in the ratio of the signal intensity value of creatine phosphate to that of inorganic phosphate and in the sum of these values. In an osteosarcoma, an initial response followed by renewed tumor growth was clearly indicated by changes in these parameters. In the short-term follow-up examination, slight spectral changes were observed during the infusion of chemotherapeutic drugs. Changes in the concentrations of phosphorus metabolites during therapy can therefore be monitored in human tumors by means of P-31 MR spectroscopy.  相似文献   
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Accumulating evidence suggests that alterations in Na, Ca, K, and other biologically relevant elements play a role in the mechanism of cell injury. The pathogenesis of experimental diabetic neuropathy is unknown but might include changes in the distribution of these elements in morphological compartments. In this study, this possibility was examined via electron-probe X-ray microanalysis to measure both concentrations of elements (millimoles of element per kilogram dry or wet weight) and cell water content (percent water) in frozen, unfixed, unstained sections of peripheral nerve from control and streptozocin-induced diabetic rats. Our results indicate that after 20 wk of experimental diabetes, mitochondria and axoplasm from myelinated axons of proximal sciatic nerve displayed diminished K and Cl content, whereas in tibial nerve, the intraaxonal levels of these elements increased. In distal sciatic nerve, mitochondrial and axoplasmic levels of Ca were increased, whereas other elemental alterations were not observed. These regional changes resulted in a reversal of the decreasing proximodistal concentration gradients for K and Cl, which exist in nondiabetic rat sciatic nerve. Our results cannot be explained on the basis of altered water. Highly distinctive changes in elemental distribution observed might be a critical component of the neurotoxic mechanism underlying diabetic neuropathy.  相似文献   
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