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J M Rothberg

Publications and source records attributed to J M Rothberg.

At least 19 recordsLinked to original sources
PubMed2001

PDGF-D, a new protease-activated growth factor.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer, fibrotic diseases and arteriosclerosis. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha, whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

3T3 Cells↗
PubMed2000

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.

Fungal Proteins↗
PubMed2000

A transmission imaging spectrograph and microfabricated channel system for DNA analysis.

In this paper we present the development of a DNA analysis system using a microfabricated channel device and a novel transmission imaging spectrograph which can be efficiently incorporated into a high throughput genomics facility for both sizing and sequencing of DNA fragments. The device contains 48 channels etched on a glass substrate. The channels are sealed with a flat glass plate which also provides a series of apertures for sample loading and contact with buffer reservoirs. Samples can be easily loaded in volumes up to 640 nL without band broadening because of an efficient electrokinetic stacking at the electrophoresis channel entrance. The system uses a dual laser excitation source and a highly sensitive charge-coupled device (CCD) detector allowing for simultaneous detection of many fluorescent dyes. The sieving matrices for the separation of single-stranded DNA fragments are polymerized in situ in denaturing buffer systems. Examples of separation of single-stranded DNA fragments up to 500 bases in length are shown, including accurate sizing of GeneCalling fragments, and sequencing samples prepared with a reduced amount of dye terminators. An increase in sample throughput has been achieved by color multiplexing.

Animals↗
PubMed2000

Differential transport of DNA by a rectified Brownian motion device.

An interdigitated electrode array (IDEA) device has been designed and used to transport DNA based on a Brownian ratchet mechanism. This migration is produced by the periodic formation of an asymmetric sawtooth electric field in the device. Oligonucleotides of 25, 50, and 100 bases in length were tested using two different array geometries. DNA transport as a function of DNA size, electric field frequency, and array geometry is shown to be in qualitative agreement with theory. Such a device could provide for DNA separations over a broad size range, and can be readily scaled as a component in a microfabricated DNA analysis system.

Animals↗
PubMed1999

DNA transport by a micromachined Brownian ratchet device.

We have micromachined a silicon-chip device that transports DNA with a Brownian ratchet that rectifies the Brownian motion of microscopic particles. Transport properties for a DNA 50-mer agree with theoretical predictions, and the DNA diffusion constant agrees with previous experiments. This type of micromachine could provide a generic pump or separation component for DNA or other charged species as part of a microscale lab-on-a-chip. A device with reduced feature size could produce a size-based separation of DNA molecules, with applications including the detection of single-nucleotide polymorphisms.

DNA↗
PubMed1999

Gene expression analysis by transcript profiling coupled to a gene database query.

We describe an mRNA profiling technique for determining differential gene expression that utilizes, but does not require, prior knowledge of gene sequences. This method permits high-throughput reproducible detection of most expressed sequences with a sensitivity of greater than 1 part in 100,000. Gene identification by database query of a restriction endonuclease fingerprint, confirmed by competitive PCR using gene-specific oligonucleotides, facilitates gene discovery by minimizing isolation procedures. This process, called GeneCalling, was validated by analysis of the gene expression profiles of normal and hypertrophic rat hearts following in vivo pressure overload.

Animals↗
PubMed1998

The Army psychological autopsy: then and now.

The conduct and reporting of an Army psychological autopsy is a complex and relatively infrequent event. The details of these reports may not be completely clear to the behavioral sciences personnel tasked with collecting the data. This paper reviews the current status of the Army psychological autopsy and contrasts it with the development of civilian psychological autopsies. The current thinking of the Department of Defense Health Affairs working group on psychological autopsies is presented. The epidemiological content of the Army psychological autopsy as a scientific resource is presented in the form of an analysis of the psychological autopsies for the 1995 Army suicide data. Suggestions for updating this unique command tool are included.

Adolescent↗
PubMed1996

Phase II trial of recombinant human interleukin-2 and interferon-alpha-2a: implications for the treatment of patients with metastatic melanoma.

BACKGROUND: An intensive in-patient Phase II study of continuous infusion recombinant human interleukin-2 (rhIL-2) 3 X 10(6) Roche units (9 MIU/m2)/day plus intramuscular injection of interferon-alpha-2a (rIFN-alpha-2a) 5 x 10(6) U/m2/day, four consecutive days per week, was performed to determine whether four consecutive weeks of treatment every 6 to 8 weeks might yield a response rate of 30 to 40%, supporting an additive or synergistic effect of these agents in patients with metastatic melanoma. METHODS: Eligibility was limited to otherwise healthy metastatic melanoma patients with no brain metastases. Tumor sites were measured at six-week intervals. Toxicity was recorded using the National Cancer Institute's common toxicity criteria. RESULTS: From 1988 through 1989, 23 patients received 47 courses of rhIL-2 plus rIFN-alpha-2a. Fifteen patients (65%) had visceral metastases. Eight patients (35%) had prior systemic chemotherapy. There were two partial responses, both after one course, for a response rate of 8% (95% confidence interval: 1% to 28%). A previously untreated patient had more than 90% diminution in extensive liver, adrenal, duodenal, and soft tissue metastases lasting 9 months. A second patient, who had failed prior chemotherapy, had a 50% reduction in lymph node metastases lasting 8 months. Median overall survival was 10.4 months (21 and 70+ months for the two responders). Cumulative reversible toxicities of debilitating fatigue, malaise, depression, poor appetite, and acute toxicities of hypotension, oliguria, infection, and cortical dysfunction were responsible for dose modifications in 16% of 188 anticipated weeks of treatment, usually near the end of the second or subsequent treatment courses. CONCLUSIONS: This study demonstrates a low response rate and lack of additive benefit for rhIL-2 and rIFN-alpha-2a administered intensively in metastatic melanoma patients. Since this biotherapy regimen, in the same dose and weekly schedule, has yielded substantial clinical activity with chemotherapeutic agents, this activity cannot be significantly attributed to the independent activity of rhIL-2 plus rIFN-alpha-alone.

Adult↗
PubMed1995

Ambulatory mental health services at a U.S. Army combat support post: the effects of the Persian Gulf War.

A study of ambulatory mental health services on a U.S. Army post where logistic support personnel are stationed compared utilization of psychiatric services before, during, and after the Persian Gulf War. Rates were calculated for service utilization for the at-risk groups from consecutive cases presenting at the post's ambulatory mental health services in the Department of Psychiatry. Our findings include a high rate of dysfunction for soldiers in training during the war; significant age, race, and sex differences between utilizers and non-utilizers throughout the study period; increased routine evaluations for military schools following the war; and significant increases in utilization of services by identified high-stress units during this conflict. Rates of utilization for a combat support post can be used for resource allocation and have implications for mental health manpower planning and stress prevention.

Adult↗
PubMed1995

Mobilization and rejection of Individual Ready Reserve personnel in Operations Desert Shield/Storm at a U.S. Army Quartermaster post.

The individual Ready Reserve (IRR) is an important component of the U.S. Army's total combat force. After Operations Desert Shield/Storm, we investigated the mobilization of soldiers with combat service support specialties from the IRR to a quartermaster training post. In the initial 2 weeks of activation prior to assignment and deployment, the soldiers went through medical and administrative screening, and general and specialized military training. During this period, a sizable portion (one-quarter) of IRR troops who reported to duty were rejected for a variety of reasons (overweight, inadequate dependent arrangements, etc.) and did not remain on active duty. Potential changes to the policies that led to these rejections are discussed.

Body Weight↗
PubMed1994

Witnessed suicides.

Suicides that take place in the presence of others have not been the topic of systematic scientific inquiry. The so-called witnessed suicides account for a small percentage of all suicides but offer a unique view into the dynamics of self-destructive behavior. An epidemiologic and forensic description of 50 witnessed suicides drawn from a 15-year series of over 1,000 cases is presented. A taxonomy is developed based on the role played by the witness and related to previous work on self-destructive behavior and its motivation. Brief vignettes are used to illustrate some of the interpersonal dynamics associated with these deaths.

Adolescent↗
PubMed1994

Use of inpatient psychiatric services on a U.S. Army combat support post during Operations Desert Shield and Desert Storm: the stress of non-deployment.

We studied the utilization of inpatient psychiatric services during Operations Desert Shield and Desert Storm (the Persian Gulf War of 1990-1991) on a U.S. Army combat support post. Inpatient psychiatric admissions and dispositions for the post's catchment area were tallied before, during, and after Operations Desert Shield and Desert Storm. Subjects included active duty soldiers (deployed soldiers were not studied while they were away from the post), their families, and retirees. Overall, there was no increase in psychiatric hospitalizations for active duty soldiers, their family members, or retirees. However, coincident with the return of soldiers from Operations Desert Shield and Desert Storm, the psychiatric proportion of all hospitalizations increased in the subpopulation of soldiers not deployed who had served less than 1 year. These soldiers in training may be more susceptible to increased stress levels associated with the return of soldiers from war because of their inadequate group bonding.

Combat Disorders↗
PubMed1994

Desert Shield deployment and social problems on a U.S. Army combat support post.

We undertook a study of selected mental health-related services at a combat support post to determine if stress levels surrounding Operations Desert Shield/Desert Storm had an effect on the utilization of these services. Our measure was the problem rate formed by adding the visits to the alcohol and drug service and the social work service. The findings (not all of which reached statistical significance in our small study) were that the problem rates were higher in those units which deployed, both before and after deployment. The pre-deployment differences in age, rank, and race between those soldiers deployed and not deployed is a finding which may help to account for the difference between units. There was a transient, but not sustained, problem rate increase immediately following return home for those units which deployed. Implications for mental health-related services staffing and directions for further research are discussed.

Adult↗
PubMed1992

Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions.

Since our characterization of the slit cDNA sequence, encoding a protein secreted by glial cells and involved in the formation of axonal pathways in Drosophila, we have discovered that the protein contains two additional sequence motifs that are highly conserved in a variety of proteins. A search of the GenPept database with the 73 amino acids at the carboxy terminus of slit revealed that this region contains significant similarity to a carboxy-terminal domain found in six other exported proteins. This observation has allowed us to define a new carboxy-terminal protein motif. In addition, comparisons with a 202 amino acid domain residing between epidermal growth factor (EGF) repeats in slit shows this region to be conserved in laminin, agrin and perlecan and, strikingly, also to lie between EGF repeats in both agrin and perlecan. Our analysis suggests this motif is involved in mediating interactions among extracellular proteins. Consistent with our previous characterization of the slit protein, both new motifs are found only in extracellular proteins. The identification of these two conserved motifs in slit reveals that the entire 1469 amino acids of the protein are made up of modular regions similar to those conserved in other extracellular proteins.

Amino Acid Sequence↗
PubMed1992

Gene patents.

Explore the source record for details and available documents.

Genes↗
PubMed1992

Parasuicidal behavior on an active duty army training post.

The incidence of suicidal behavior among active duty Army personnel at a training post has not been the subject of analysis since the advent of the all-volunteer military. A review of admissions over 16 consecutive months showed most of the behaviors to be parasuicidal, with low levels of lethality and high rescuability. Compared to previously published studies, the characteristics of these soldiers are little changed over the past 25 years. This report suggests a standard method for handling suicidal behavior which includes an active role for psychiatric consultation to units and commanders.

Adjustment Disorders↗