Harvard University

About: Harvard University is a education organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 208150 authors who have published 530388 publications receiving 38152182 citations. The organization is also known as: Harvard & University of Harvard.

An Integrated View of Copy Number and Allelic Alterations in the Cancer Genome Using Single Nucleotide Polymorphism Arrays

Abstract: Changes in DNA copy number contribute to cancer pathogenesis. We now show that high-density single nucleotide polymorphism (SNP) arrays can detect copy number alterations. By hybridizing genomic representations of breast and lung carcinoma cell line and lung tumor DNA to SNP arrays, and measuring locus-specific hybridization intensity, we detected both known and novel genomic amplifications and homozygous deletions in these cancer samples. Moreover, by combining genotyping with SNP quantitation, we could distinguish loss of heterozygosity events caused by hemizygous deletion from those that occur by copy-neutral events. The simultaneous measurement of DNA copy number changes and loss of heterozygosity events by SNP arrays should strengthen our ability to discover cancer-causing genes and to refine cancer diagnosis.

The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose.

Abstract: The major reabsorptive mechanism for D-glucose in the kidney is known to involve a low affinity high capacity Na+/glucose cotransporter, which is located in the early proximal convoluted tubule segment S1, and which has a Na+ to glucose coupling ratio of 1:1. Here we provide the first molecular evidence for this renal D-glucose reabsorptive mechanism. We report the characterization of a previously cloned human kidney cDNA that codes for a protein with 59% identity to the high affinity Na+/glucose cotransporter (SGLT1). Using expression studies with Xenopus laevis oocytes we demonstrate that this protein (termed SGLT2) mediates saturable Na(+)-dependent and phlorizin-sensitive transport of D-glucose and alpha-methyl-D-glucopyranoside (alpha MeGlc) with Km values of 1.6 mM for alpha MeGlc and approximately 250 to 300 mM for Na+, consistent with low affinity Na+/glucose cotransport. In contrast to SGLT1, SGLT2 does not transport D-galactose. By comparing the initial rate of [14C]-alpha MeGlc uptake with the Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the Na+ to glucose coupling ratio of SGLT2 is 1:1. Using combined in situ hybridization and immunocytochemistry with tubule segment specific marker antibodies, we demonstrate an extremely high level of SGLT2 message in proximal tubule S1 segments. This level of expression was also evident on Northern blots and likely confers the high capacity of this glucose transport system. We conclude that SGLT2 has properties characteristic of the renal low affinity high capacity Na+/glucose cotransporter as previously reported for perfused tubule preparations and brush border membrane vesicles. Knowledge of the structural and functional properties of this major renal Na+/glucose reabsorptive mechanism will advance our understanding of the pathophysiology of renal diseases such as familial renal glycosuria and diabetic renal disorders.

The structure of clusters of galaxies observed with Einstein

Abstract: Imaging observations from the Einstein Observatory are used to determine properties of galactic clusters and the intracluster gas. The hydrostatic-isothermal gas model is applied to obtain the cluster core radius, the limiting slope of the X-ray surface brightness distribution, and the presence and magnitude of a central luminosity excess above that predicted from the model when fit to the outer regions of the cluster. It is concluded that clusters can be divided into two basic families, one with small core radii and X-ray emission centered on a central dominant galaxy, and one with larger core radii and generally no central, stationary bright galaxy. The former type probably begins to form in the early stages of a cluster's dynamical evolution. The intracluster gas has a larger scale height than that of the galaxies based on the fit of the hydrostatic-isothermal model to the X-ray surface brightness profiles.

Long-term outcomes of surgical and nonsurgical management of lumbar spinal stenosis: 8 to 10 year results from the maine lumbar spine study.

Abstract: Study design A prospective observational cohort study. Objective To assess long-term outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically. Summary of background data The relative benefit of various treatments for lumbar spinal stenosis is uncertain. Surgical treatment has been associated with short-term improvement, but recurrence of symptoms has been documented. Few studies have compared long-term outcomes of surgical and nonsurgical treatments. Methods Patients recruited from the practices of orthopaedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with follow-up questionnaires mailed at regular intervals over 10 years. Clinical data were obtained at baseline from a physician questionnaire. Most patients initially undergoing surgery had a laminectomy without fusion performed. Outcomes including patient-reported symptoms of leg and back pain, functional status, and satisfaction were assessed at 8- to 10-year follow-up. Primary analyses were based on initial treatment received with secondary analyses examining actual treatment received by 10 years. Results Of 148 eligible consenting patients initially enrolled, 105 were alive after 10 years (67.7% survival rate). Among surviving patients, long-term follow-up between 8 and 10 years was available for 97 of 123 (79%) patients (including 11 patients who died before the 10-year follow-up but completed a 8 or 9 year survey); 56 of 63 (89%) initially treated surgically and 41 of 60 (68%) initially treated nonsurgically. Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically. Outcomes at 1 and 4 years favored initial surgical treatment. After 8 to 10 years, a similar percentage of surgical and nonsurgical patients reported that their low back pain was improved(53% vs. 50%, P = 0.8), their predominant symptom (either back or leg pain) was improved (54% vs. 42%, P = 0.3), and they were satisfied with their current status (55% vs. 49%, P = 0.5). These treatment group findings persisted after adjustment for other determinants of outcome in multivariate models. However, patients initially treated surgically reported less severe leg pain symptoms and greater improvement in back-specific functional status after 8 to 10 years than nonsurgically treated patients. By 10 years, 23% of surgical patients had undergone at least one additional lumbar spine operation, and 39% of nonsurgical patients had at least one lumbar spine operation. Patients undergoing subsequent surgical procedures had worse outcomes than those continuing with their initial treatment. Outcomes according to actual treatment received at 10 years did not differ because individuals undergoing additional surgical procedures had worse outcomes than those continuing with their initial treatment. Conclusions Among patients with lumbar spinal stenosis completing 8- to 10-year follow-up, low back pain relief, predominant symptom improvement, and satisfaction with the current state were similar in patients initially treated surgically or nonsurgically. However, leg pain relief and greater back-related functional status continued to favor those initially receiving surgical treatment. These results support a shared decision-making approach among physicians and patients when considering treatment options for lumbar spinal stenosis.