Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects

CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. OBJECTIVE: To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS: Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. SETTING: University-based medical centers and affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. RESULTS: The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS: Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.     

Quantal release at visualized terminals of a crayfish motor axon: intraterminal and regional differences

Synaptic transmission was measured at visualized terminal varicosities of the motor axon providing the sole excitatory innervation of the "opener" muscle in walking legs of crayfish (Procambarus clarkii Girard). Two questions were addressed: 1) How uniform is quantal emission at different locations along terminals innervating a single muscle fiber, and 2) can differences in quantal emission account for the different excitatory postsynaptic potential (EPSP) amplitudes generated by terminals localized in defined regions of the muscle? Extracellular "macropatch" electrodes were placed over individual varicosities, viewed after brief exposure to a fluorescent dye, and synaptic currents were recorded to determine quantal content of transmission. Along terminals supplying a single muscle fiber, nonuniform release was found: Varicosities closer to the point of origin of the terminal branch released more transmitter than those located more distally. Quantal content was higher for varicosities of the muscle's proximal region (where large EPSPs occur) than for varicosities of the central region (where small EPSPs occur). The probability of transmitter release per synapse is estimated to be greater for the proximal varicosities. At low frequencies of stimulation, quantal content per muscle fiber is two to four times larger in the proximal region. Taken in conjunction with a twofold higher mean input resistance for the proximal muscle fibers, the difference in quantal content can account for a four- to eightfold difference in EPSP amplitude. The observed mean EPSP amplitude is at least eight times larger in the proximal region. We discuss factors contributing to differences in EPSP amplitudes.     

Sampling Search-Engine Results

We consider the problem of efficiently sampling Web search engine query results. In turn, using a small random sample instead of the full set of results leads to efficient approximate algorithms for several applications, such as:

Illness and injury in family day care: a seasonal survey

Many mothers with children under age 6 are employed and it is not usually feasible for a parent to stay home with a child who is mildly ill. Such ill children likely remain in child day care programs. The extent to which this occurs and the management of these children in family day care was studied. Over the course of a year, 1 to 3 visits were made to 714 family day care homes in order to survey providers. With enrollments ranging between 0 and 18 children per day care home at the time of each visit, information on 3,630 "child enrollment days" was collected. The median age of children in care was 2 years. An average of 16% of all children were ill on any one day (with seasonal variation); 1% were injured. Of ill children, 82% attended day care that day, 49% had contacted a physician about that illness, and 28% were administered a medication at the day care setting. Twenty-one percent of children receiving medication in day care had no contact with a physician for that illness. These data show that mild childhood illnesses are routinely managed by child day care providers. Physicians who traditionally limit their illness-management education to parents need to recognize the health education and consultation needs of day care providers.     

Graph structure in the Web

The study of the Web as a graph is not only fascinating in its own right, but also yields valuable insight into Web algorithms for crawling, searching and community discovery, and the sociological phenomena which characterize its evolution. We report on experiments on local and global properties of the Web graph using two AltaVista crawls each with over 200 million pages and 1.5 billion links. Our study indicates that the macroscopic structure of the Web is considerably more intricate than suggested by earlier experiments on a smaller scale.     

Auditory-phonetic projection and lexical structure in the recognition of sine-wave words.

Speech remains intelligible despite the elimination of canonical acoustic correlates of phonemes from the spectrum. A portion of this perceptual flexibility can be attributed to modulation sensitivity in the auditory-to-phonetic projection, although signal-independent properties of lexical neighborhoods also affect intelligibility in utterances composed of words. Three tests were conducted to estimate the effects of exposure to natural and sine-wave samples of speech in this kind of perceptual versatility. First, sine-wave versions of the easy and hard word sets were created, modeled on the speech samples of a single talker. The performance difference in recognition of easy and hard words was used to index the perceptual reliance on signal-independent properties of lexical contrasts. Second, several kinds of exposure produced familiarity with an aspect of sine-wave speech: (a) sine-wave sentences modeled on the same talker; (b) sine-wave sentences modeled on a different talker, to create familiarity with a sine-wave carrier; and (c) natural sentences spoken by the same talker, to create familiarity with the idiolect expressed in the sine-wave words. Recognition performance with both easy and hard sine-wave words improved after exposure only to sine-wave sentences modeled on the same talker. Third, a control test showed that signal-independent uncertainty is a plausible cause of differences in recognition of easy and hard sine-wave words. The conditions of beneficial exposure reveal the specificity of attention underlying versatility in speech perception. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Follicular and Hurthle cell carcinomas of the thyroid: a comparative study

University of Texas M. D. Anderson Cancer Center cases filed as Hurthle cell and follicular carcinoma were reviewed. Requirements for including a case in the study were that the diagnosis of Hurthle cell or follicular carcinoma be confirmed, that histologic material and clinical information be adequate, and that there be at least 9 years of follow-up. The study group included 18 cases of Hurthle cell carcinoma and 33 cases of follicular carcinoma. Ten of the Hurthle cell carcinomas had extrathyroid invasion, three had intrathyroid invasion, and five were encapsulated (i.e., they had intracapsular invasion only). In the follicular carcinoma group, 5 tumors had extrathyroid invasion, 14 had intrathyroid invasion, and 14 were encapsulated. When the cases were stratified according to extent of invasion in this manner, there was no statistically significant difference in rate of local recurrence, rate of metastasis (either regional lymph node or distant), or patient survival between Hurthle cell carcinoma and follicular carcinoma. Other variables including patient age and sex, treatment differences, tumor size, vascular invasion, predominant growth pattern (follicular versus solid-trabecular), nuclear size and pleomorphism, mitotic rate, and tumor necrosis did not provide significant additional prognostic information. Metastases of both Hurthle cell and follicular carcinoma were mostly distant and predominantly involved bone and lung. Behavioral differences between Hurthle cell and follicular carcinoma that were not statistically significant included a higher rate of local recurrence in Hurthle cell carcinoma with intrathyroid invasion, more frequent occurrence of regional lymph node metastasis in Hurthle cell carcinoma with extrathyroid invasion, and absence of distant metastasis and death caused by tumor in encapsulated Hurthle cell carcinoma. Five follicular carcinomas and one Hurthle cell carcinoma appeared to have arisen within an adenoma.