Placental trophoblasts resist infection by multiple human immunodeficiency virus (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV replication after provirus transfection

Whether cell-free human immunodeficiency virus type 1 (HIV-1) can productively infect placental trophoblasts (which in turn could transmit the virus into the fetal circulation) is controversial but essential to know for the evaluation of alternative routes (such as cell-mediated infection or trophoblast damage). We have addressed infection factors such as cell purity, source, culture methods, and activation states as well as virus variant and detection methods to conclusively determine the outcome of trophoblast challenge by free virus. Pure (> 99.98%) populations of trophoblasts from 11 different placentas were challenged at a multiplicity of infection (MOI) as high as 6 with five different HIV-1 variants, three of which are non-syncytium-forming, macrophage-tropic isolates from infected infants, with and without coinfection with cytomegalovirus; these preparations were monitored for productive infection for up to 3 weeks after challenge by five different criteria, the most sensitive of which were cocultivation with target cells that can detect virus at an MOI of 10(-7) and HIV DNA PCR that detects 30 virus copies per 10(5) cells. Infection was never detected. However, molecularly cloned T-cell (pNL4-3)- and macrophage (pNLAD8)-tropic provirus plasmids, when transfected into primary trophoblasts, yielded productive infections, indicating that trophoblasts do not suppress late-stage virus replication and assembly. Because of the purity of the trophoblast preparations, the extended length of the infection culture period, the number of trophoblast preparations and virus types examined, the sensitivity of the bioassays and molecular detection assays, and the observations that trophoblasts can support virus replication from provirus, the results of this study strongly argue that free virus cannot infect primary villous trophoblasts.     

Transient rigid lens-induced striae in keratoconus

We have observed spontaneous development of striae and an enhanced visibility of them after placing rigid gas permeable contact lenses on six patients suspected of having early keratoconus. These fine folds subside upon removal of the rigid lens. This observation assists clinicians with the differential diagnosis of irregular astigmatism when the definitive biomicroscopic signs of keratoconus are either not present or are so subtle that their presence is questionable. Although these striae may not occur in all patients suspected of having early keratoconus, we find that observation of the posterior cornea in the presence of a rigid lens will often confirm the diagnosis of keratoconus. We have not seen similar striae in patients whose clinical presentation is not consistent with early keratoconus.     

Parathyroid hormone--related protein (PTHrP) is an epidermal growth factor-regulated secretory product of human prostatic epithelial cells

Integral membrane proteins have one or more transmembrane alpha-helical domains and carry out a variety of functions such as enzyme catalysis, transport across membranes, transducing signals as receptors of hormones and growth factors, and energy transfer in ATP synthesis. These transmembrane domains are not mere structural units anchoring the protein to the lipid bilayer but seem to-contribute in the overall activity. Recent findings in support of this are described using some typical examples-LDL receptor, growth factor receptor tyrosine kinase, HMG-CoA reductase, F0-ATPase and adrenergic receptors. The trends in research indicate that these transmembrane domains participate in a variety of ways such as a linker, a transducer or an exchanger in the overall functions of these proteins in transfer of materials, energy and signals.     

Refractory giant cell arteritis with spinal cord infarction

We report an elderly patient with aggressive steroid-refractory giant cell arteritis manifesting as myelopathy and bilateral visual loss while on treatment. Pathologically, spinal cord infarction was observed and was due to extensive necrotizing granulomatous arteritis of spinal arteries. Spinal cord damage in giant cell arteritis is rare. One prior autopsy report of spinal cord infarction in giant cell arteritis did not identify vasculitic changes in the spinal arteries.     

Glucocorticoids may enhance oxygen radical-mediated neurotoxicity

Modern populations are constantly exposed to a variety of compounds in the workplace and the environment that promote formation of reactive oxygen species (ROS) within susceptible tissues. Due to its high oxygen consumption, the brain may be particularly vulnerable to oxidative damage and degeneration. Agents that impact cellular oxidative homeostasis would therefore be expected to alter the toxicity of ROS generating compounds. We are testing this hypothesis using endogenous stress hormones, glucocorticoids, to perturb neuronal homeostasis, and adriamycin to generate ROS. Glucocorticoids (GCs) are hormones secreted by the adrenals in response to stress, and are also prescribed clinically to control inflammatory and autoimmune disorders in millions of people annually. Therefore, high GC levels may not be uncommon in individuals exposed to low levels of toxic compounds. Also, GCs appear to act on cellular pathways relevant to ROS as seen by their potentiation of neurodegeneration following insults such as stroke, hypoglycemia and seizure. Using rat primary neuronal culture, we determined neuronal susceptibility to adriamycin toxicity by cell counting (using MAP-2 staining). Dichlorofluorescein fluorescence confirmed ROS generation after adriamycin administration. Physiological levels of GCS (up to mM concentrations) in the culture media exacerbated both adriamycin toxicity and ROS generation. We hypothesize that GCs may exacerbate the toxicity of three neurotoxins whose mechanisms of action overlap GC pathways.     

Apolipoprotein e4 allele and cognitive decline in elderly men

OBJECTIVES: To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population. DESIGN: Population based cohort investigated in 1990 and in 1993. SETTING: Zutphen, the Netherlands. SUBJECTS: Representative cohort of 538 Dutch men aged 70-89 at baseline. MAIN OUTCOME MEASURES: Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years. RESULTS: The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele. CONCLUSIONS: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.     

New look at force-frequency relationship of human skeletal muscle: effects of fatigue

16-Fluoropalmitic acid was synthesized from 16-hydroxypalmitic acid using diethylaminosulfur trifluoride. This monofluorinated fatty acid then was used to make 1-palmitoyl-2-[16-fluoropalmitoyl]-phosphatidylcholine (F-DPPC) as a fluorinated analog of dipalmitoylphosphatidylcholine (DPPC). Surprisingly, we found that the phase transition temperature (Tm) of F-DPPC occurs near 50 degrees C, approximately 10 degrees C higher than its nonfluorinated counterpart, DPPC, as judged by both differential scanning calorimetry and infrared spectroscopy. The pretransition observed for DPPC is absent in F-DPPC. A combination of REDOR, rotational-echo double-resonance, and conventional solid-state NMR experiments demonstrates that F-DPPC forms a fully interdigitated bilayer in the gel phase. Electron paramagnetic resonance experiments show that below Tm, the hydrocarbon chains of F-DPPC are more motionally restricted than those of DPPC. X-ray scattering experiments confirm that the thickness and packing of gel phase F-DPPC is similar to that of heptanetriol-induced interdigitated DPPC. F-DPPC is the first phosphoglyceride containing sn-1 and sn-2 ester-linked fatty acyl chains of equal length that spontaneously forms interdigitated bilayers in the gel state in the absence of inducing agents such as alcohols.     

Female voice communications in high levels of aircraft cockpit noises--Part I: spectra, levels, and microphones

HYPOTHESIS: Female produced speech, although more intelligible than male speech in some noise spectra, may be more vulnerable to degradation by high levels of some military aircraft cockpit noises. The acoustic features of female speech are higher in frequency, lower in power, and appear more susceptible than male speech to masking by some of these military noises. Current military aircraft voice communication systems were optimized for the male voice and may not adequately accommodate the female voice in these high level noises. METHODS: This applied study investigated the intelligibility of female and male speech produced in the noise spectra of four military aircraft cockpits at levels ranging from 95 dB to 115 dB. The experimental subjects used standard flight helmets and headsets, noise-canceling microphones, and military aircraft voice communications systems during the measurements. RESULTS: The intelligibility of female speech was lower than that of male speech for all experimental conditions; however, differences were small and insignificant except at the highest levels of the cockpit noises. Intelligibility for both genders varied with aircraft noise spectrum and level. Speech intelligibility of both genders was acceptable during normal cruise noises of all four aircraft, but improvements are required in the higher levels of noise created during aircraft maximum operating conditions. CONCLUSIONS: The intelligibility of female speech was unacceptable at the highest measured noise level of 115 dB and may constitute a problem for other military aviators. The intelligibility degradation due to the noise can be neutralized by use of an available, improved noise-canceling microphone, by the application of current active noise reduction technology to the personal communication equipment, and by the development of a voice communications system to accommodate the speech produced by both female and male aviators.     

Constipation in the elderly

Constipation affects as many as 26 percent of elderly men and 34 percent of elderly women and is a problem that has been related to diminished perception of quality of life. Constipation may be the sign of a serious problem such as a mass lesion, the manifestation of a systemic disorder such as hypothyroidism or a side effect of medications such as narcotic analgesics. The patient with constipation should be questioned about fluid and food intake, medications, supplements and homeopathic remedies. The physical examination may reveal local masses or thrombosed hemorrhoids, which may be contributing to the constipation. Visual inspection of the colon is useful when no obvious cause of constipation can be determined. Treatment should address the underlying abnormality. The chronic use of certain treatments, such as laxatives, should be avoided. First-line therapy should include bowel retraining, increased dietary fiber and fluid intake, and exercise when possible. Laxatives, stool softeners and nonabsorbable solutions may be needed in some patients with chronic constipation.     

Management of liver adenomatosis: results with a conservative surgical approach

Liver adenomatosis is defined by the presence of multiple hepatic adenomas (more than three lesions). The natural history and treatment of liver adenomatosis are not yet well defined. The Mayo Clinic (Rochester, MN) experience with liver adenomatosis in the past 11 years was reviewed and a rational treatment approach is presented. Records from patients with liver adenomatosis and hepatic adenoma seen at the Mayo Clinic from January 1986 to June 1997 were reviewed. Estrogen- and progesterone-receptor status was assessed by immunohistochemistry. Eight women with liver adenomatosis were identified. All patients had undergone surgical treatment. Abdominal pain was the presenting symptom in 87.5% of the patients with adenomatosis and in 42.1% of the patients with hepatic adenoma. Tumor bleeding was present in 62.5% of the patients with adenomatosis and in 26.3% of the patients with hepatic adenomas. Bleeding occurred predominantly in lesions greater than 4 cm. All patients with liver adenomatosis reported improvement of symptoms after surgery, and the mean bleeding-free period after resection in 5 patients was 52.6 +/- 23.6 months. In 6 patients, estrogen receptor-positive and estrogen receptor-negative tumors were identified in the same liver. Based on the good outcome after resection in symptomatic patients with liver adenomatosis, we recommend resection of large (>/=5 cm) or symptomatic lesions with observation of smaller lesions (相似文献