bluuebunny/crossref_metadata_2025 huggingface dataset:
Analog and Digital
SQUID
Sensors
Authors: Radparvar Masoud
Published: October 2003

Superconducting QUantum Interference Devices (SQUIDs) are extremely sensitive detectors of magnetic flux and can be used as low noise amplifiers for a variety of applications such as high resolution magnetometers, susceptometers, neuromagnetometers, motion detectors, ultrasensitive voltmeters, pico‐ammeters, readout of cryogenic detectors, and biomagnetic measurements. A SQUID is a superconducting ring interrupted by one or two Josephson tunnel junctions made of a superconductor such as niobium. Nb is the material of choice for superconducting circuits, because it has the highest critical temperature among the elemental superconductors (9.3 K). This alleviates certain uniformity and repeatability concern that must be taken into account when using compound superconductors. Josephson tunnel junctions using niobium as electrodes and thermally oxidized aluminum as tunnel barriers have been investigated rather extensively and have been brought to a state of maturity suitable for medium scale integrated circuits by several laboratories.

A typical SQUID circuit process uses 3–10 µm
2
area Josephson junctions with critical current density of 100–1000 A/cm
2
. These circuits are fabricated by a multilayer process with all niobium electrodes and wiring, aluminum oxide tunnel barrier, Mo or Au resistors, Au metallization, and SiO
2
insulating layers.
Still Photography
Authors: Kraus Russell
Published: October 2003

Camera still imaging is the use of a lighttight device that holds a light‐sensitive detector and permits controlled exposure to light by using a lens that has diaphragm control and a shutter, a device that controls the length of exposure. Controlled exposure is simply taken as an amount of light during a continuous period of time that produces a desired amount of density on the film after development. The desired amount of exposure is typically determined by either experimental methods know as sensitometry or through trial and error.

The shutter range for exposure can be between several hours and 1/8000th of a second, excluding the use of a stroboscopic flash that permits exposure times shorter than a millionth of a second.

The image has a size or format of standard dimensions: 16‐mm (subminiature), 35‐mm(miniature), and 60‐mm (medium format). These are commonly referred to as roll film formats. Four inches by five inches, 5 × 7 inches, and 8 × 10 inches are three standard sheet film sizes. A view camera, monorail camera, or folding type is used to expose each sheet one at a time. Folding type, technical cameras that have a baseboard can be single sheet exposure or can adapt to a roll film back of reduced dimensions. All current camera systems can either replace their film detectors with digital detectors or themselves are replaced entirely by a digital version.

The nature of current still photography can be seen in its applied aspects: Documentary, reportage, scientific recording, commercial/ advertising, and fine art shooting are the primary realms of the professional photographer. In each activity, care is given to the materials, equipment, and processes by which a specific end is achieved. Scientific and technical photographers use the photographic process as a data collection tool where accuracy in time and space is of paramount importance. Photography for the commercial, documentary, and fine arts photographers has never been an objective and simple recording of an event or subject. This type of photography has as much purpose and artifice as commercial/advertising shooting. The visual selling of product by imagery designed to elicit an emotional response has been an integral part of advertising for more than 100 years. The psychology of photography has remained relatively the same during this time, albeit photocriticism has had many incarnations, but the technology that has made photography the tool it is has changed very rapidly and innovatively during the last century. The current digital evolution in photography will further advance the tools available and alter the way images are captured and displayed.
Tomographic Image Formation Techniques
Authors: Herman Gabor T.
Published: October 2003

Computerized tomography is the process of reconstructing the interiors of objects from collected data based on transmitted or emitted radiation. This article explains the nature of the reconstruction problem and present computer algorithms used for achieving the reconstructions and approaches for evaluating the efficacy of such algorithms are discussed.

This article cover some of the basic principles behind tomographic imaging, including such topics as the Radon transform, interpolation for backprojection (both modified cubic spline and sinc), the Ram–Lak filter, missing angle techniques, maximum entropy techniques, resolution, the signal‐to‐noise ratio, and artifact limitations.
Weather Radar
Authors: Rauber Robert M.
Published: October 2003

This article contains a brief overview of the history of meteorological radars, presents the operating principles of these radars, and explains important applications of radar in the atmospheric sciences. Meteorological radars transmit short pulses of electromagnetic radiation at microwave or radio frequencies and detect energy backscattered toward the radar's antenna by scattering elements in the atmosphere. Radiation emitted by radar is scattered by water and ice particles, insects, other objects in the path of the beam, and refractive index heterogeneities in air density and humidity. The returned signal is the combination of radiation backscattered toward the radar by each scattering element within the volume illuminated by a radar pulse. Meteorologists use the amplitude, phase, and polarization state of the backscattered energy to deduce the location and intensity of precipitation, the wind speed in the direction of the radar beam, and precipitation characteristics, such as rain versus hail.
X
‐
R
ay Telescope
Authors: Cash Webster
Published: October 2003

An X‐ray telescope is an optic that is used to focus and image x‐rays in the manner of a conventional telescope for visible light astronomy. X‐ray telescopes are exclusively the domain of X‐ray astronomy, the discipline that studies high energy emissions from objects in space. A telescope, by its very nature, is for studying objects at large distances, concentrating their radiation, and magnifying their angular extent. Since X‐rays cannot travel large distances through the atmosphere of the Earth, their function can only be used in spacecraft, observing targets through the vacuum of space.

X‐rays penetrate matter and are used for imaging of the interior of the human body. Unfortunately, this means that X‐rays also tend to penetrate telescope mirrors, making the mirror worthless for astronomy. But, by use of a specialized technique called grazing incidence, telescopes can be made to reflect, and astronomy can be performed. In this article, we describe the basic techniques used to build x‐ray telescopes for X‐ray astronomy.

X‐ray astronomy, because it must be performed above the atmosphere, is a child of the space program. Telescopes are carried above the atmosphere by rockets and used to study the Sun, the planets, and objects in the depths of space. These telescopes have provided a different view of the hot and energetic constituents of the universe, and produced the key observations to establish the existence of black holes.

Various telescopes are described, e.g., Thin mirror telescopes, Kirk‐Baez telescopes, X‐ray interferometric telescopes, and Multilayer telescopes. Various missions involving these telescopes are discussed.
Acoustic Sources or Receiver Arrays
Authors: Thompson William
Published: October 2003

This article discusses the directional response characteristics (i.e., the beam patterns or directivity patterns) of arrays of time harmonic acoustic sources. A wonderful consequence of the acoustic reciprocity theorem, however, is that the directional response pattern of a transducer used as a source is the same as its directional response pattern used as a receiver. The arrays in question begin with the simplest, two identical point sources, and build up to line arrays that contain many point sources, continuous two dimensional arrays of sources, and discrete arrays of finite sized sources. Topics such as beam width of the main lobe, amplitudes of the side lobes, amplitude weighting to reduce the side lobes, and beam tilting and its consequences are discussed. Again, although the emphasis will be on the response of arrays of sources, the result (the directivity pattern) is the same for the same array used as a receiver. Harmonic time dependence of the form exp(
j
ω
t
) at circular frequency ω is assumed and suppressed throughout most of the following discussion.
Television Broadcast Transmission Standards
Authors: Godger Alan S. , Redford James R.
Published: October 2003

Since the invention of television, the images and sound have been captured, processed, transmitted, received, and displayed using analog technology, where the picture and sound elements are represented by signals that are proportional to the image amplitude and sound volume.

More recently, as solid‐state technology has developed, spurred primarily by the development of computers, digital technology has gradually been introduced into handling the television signal, both for image and sound. The digital electric signal representing the various elements of the image and sound is composed of binary numbers that represent the image intensity, color, and so on, and the sound characteristics.

Many portions of television systems are now hybrid combinations of analog and digital, and it is expected that eventually all television equipment will be fully digital, except for the transducers, cameras, and microphones (whose inputs are analog) and the television displays and loudspeakers (whose outputs are analog).

The currently used broadcast television transmission standards [National Television Systems Committee (NTSC), phase alternate line (PAL) and sequential and memory (SECAM)] for 525‐ and 625‐line systems were designed around analog technology, and although significant portions of those broadcast systems are now hybrid analog/digital or digital, the “over the air” transmission system is still analog. Furthermore, other than for “component” processed portions of the system, the video signals take the same “encoded” form from studio camera to receiver and conform to the same standard.

The recently developed ATSC Digital Television Standard, however, uses digital technology for “over the air” transmission, and the digital signals used from the studio camera to the receiver represent the same image and sound, but differ in form in portions of the transmission system. This variation is such that in the studio, maximum image and sound information is coded digitally, but during recording, special effects processing, distribution around a broadcast facility, and transmission, the digital signal is “compressed” to an increasing extent as it approaches its final destination at the home. This permits practical and economical handling of the signal.
Terahertz Electric Field Imaging
Authors: Zhang X.‐C.
Published: October 2003

Various frequencies are spaced along the frequently used electromagnetic spectrum, including microwaves, infrared, visible light, and X rays. Terahertz radiation between microwave and infrared frequencies lies. In the electromagnetic spectrum, radiation at 1 THz has a period of 1 ps, a wavelength of 300 µm, a wave number of 33 cm−1, photon energy of 4.1 meV, and an equivalent temperature of 47.6 K. In the same way that visible light can create a photograph, radio waves can transmit sound, and X rays can see shapes within the human body, terahertz waves (Trays) can create pictures and transmit information.

Until recently, however, the very large terahertz portion of the spectrum has not been particularly useful because there were neither suitable emitters to send out controlled terahertz signals nor efficient sensors to collect them and record information. Recent developments in terahertz time‐domain spectroscopy and related terahertz technologies now lead one to view the world in a new way. As a result of developing research, terahertz radiation now has widespread potential applications in medicine, microelectronics, agriculture, forensic science, and many other fields.

Three properties of THz wave radiation triggered research to develop this frequency band for applications and are discussed.

Coherent terahertz time‐domain spectroscopy that has an ultrawide bandwidth provides a new method for characterizing the electronic, vibronic, and compositional properties of solid, liquid, and gas phase materials, as well as flames and flows. In theory, many biological and chemical compounds have distinct signature responses to terahertz waves due to their unique molecular vibrations and rotational energy levels, this implies that their chemical compositions might be examined using a terahertz beam.

A T‐ray imaging modality would produce images that have “component contrast” enabling analysis of the water content and composition of tissues in biological samples. Such capability presents tremendous potential to identify early changes in composition and function as a precursor to specific medical investigations and treatment. Moreover, in conventional optical transillumination techniques that use near‐infrared pulses, large amounts of scattering can spatially smear out the objects to be imaged. T‐ray imaging techniques, due to their longer wavelengths, can provide significantly enhanced contrast as a result of low scattering (Rayleigh scattering).
Hybrid Semiconductor Pixel Detectors for Low‐ and Medium‐EnergyX‐ and Gamma‐Ray Single Photon Imaging Using the Medipix Read‐Out Chip
Authors: Russo Paolo
Published: October 2003

After a brief description of microstrip and pixel detectors for radiation imaging with X‐rays and gamma‐rays, the functionality, physical response, and imaging performance of the hybrid pixel detectors based on the Medipix1 photon counting chip for such diverse imaging applications such as digital mammography, synchrotron X‐ray radiation, nuclear medicine, and so on are described. It is concluded that such hybrid pixel detectors, originated from high‐energy physics, have great potential for specific scientific and industrial X‐ and gamma‐ray imaging applications and that the fabrication of large detector arrays or mosaic of detectors for large area imaging is still the main open problem with hybrid detectors.
Pharmacogenetics and mood stabilization in bipolar disorder
Authors: Ruzickova Martina , Turecki Gustavo , Alda Martin
Published: October 2003

Bipolar disorder is a severe psychiatric disease characterized by varying treatment response among individual patients. Effects of certain treatments, for instance, lithium, can be predicted from clinical characteristics of patients and their family histories. This led to a suggestion that a treatment response could identify subtypes of bipolar disorder particularly suited for gene‐mapping studies. In this paper we review family and molecular studies of bipolar disorder responsive to lithium, as well as studies aiming to identify polymorphisms associated with the treatment response itself. While molecular genetic research and gene expression studies promise to bring new insights into the pathophysiology of the illness and the nature of treatment response, and thus provide new information for better treatment of bipolar disorder in the future, results from family studies and studies of clinical correlates of treatment response may already be utilized in the management of bipolar disorder. © 2003 Wiley‐Liss, Inc.
Studies of offspring of parents with bipolar disorder
Authors: Chang Kiki , Steiner Hans , Ketter Terence
Published: October 2003

Children and adolescents who are the biological offspring of individuals with bipolar disorder (BD) (bipolar offspring) represent a population rich in potential for revealing important aspects in the development of BD. Multiple cross‐sectional assessments of psychopathology in bipolar offspring have confirmed high incidences of BD, as well as mood and behavioral disorders, and other psychopathology in this population. Longitudinal studies of offspring have begun to shed light on precursors of BD development. Other assessments of bipolar offspring have included dimensional reports of psychiatric and psychosocial functioning, temperament assessments, and descriptions of family environments and parenting styles. Neurobiological studies in bipolar offspring are just beginning to yield findings that may be related to the underlying neuropathophysiology of BD. The future holds promise for longitudinal studies of bipolar offspring incorporating all of these facets, including genetic analyses, to further elucidate the factors involved in the evolution of BD. © 2003 Wiley‐Liss, Inc.
Genetic linkage and association studies in bipolar affective disorder: A time for optimism
Authors: Schulze Thomas G. , McMahon Francis J.
Published: October 2003

Genetic research on complex diseases is beginning to bear fruit, with the successful identification of candidate susceptibility genes in diabetes, asthma, and other illnesses. Similar success is on the horizon for bipolar affective disorder (BPAD), but significant challenges remain. In this review, we outline the basic concepts of linkage and association mapping for complex phenotypes. We point out important caveats inherent in both approaches, and review guidelines on the interpretation of linkage statistics and significance thresholds. We then apply these concepts to an evaluation of the present status of genetic linkage and association studies in BPAD. The challenges posed by locus heterogeneity, phenotype definition, and sample size requirements are given a detailed treatment. Despite these challenges, we argue that the way ahead remains firmly rooted in linkage studies, complemented by association studies in linked regions. This is the only truly genome‐wide approach currently available; it has succeeded in other complex phenotypes, and it is the surest strategy for mapping susceptibility genes in BPAD. Once these genes are identified, genetic mapping methods will yield to the other methods of 21st‐century molecular biology as we begin to elucidate the pathophysiology of BPAD. © 2003 Wiley‐Liss, Inc.
Reoperations after prophylactic mastectomy with or without implant reconstruction
Authors: Zion Sara M. , Slezak Jeffrey M. , Sellers Thomas A. , Woods John E. , Arnold Phillip G. , Petty Paul M. , Donohue John H. , Frost Marlene H. , Schaid Daniel J. , Hartmann Lynn C.
Published: October 2003

BACKGROUND

The authors characterized the unanticipated reoperations after prophylactic mastectomy, with or without implant reconstruction.

METHODS

The surgical cohort was comprised of 1417 women with a family history of breast carcinoma. The women received a prophylactic mastectomy with (bilateral,n= 593; contralateral,n= 506) or without reconstruction (n= 318) at the Mayo Clinic (Rochester, MN) between 1960 and 1993. Reoperations and indications for reoperation were compiled from medical records and a patient survey.

RESULTS

Three hundred eighteen women received a bilateral (n= 39) or contralateral (n= 279) prophylactic mastectomy without reconstruction. With a median follow‐up of 15 years, 18 women (6%) required reoperation. Most of these reoperations occurred within the first year after prophylactic mastectomy. Five hundred ninety‐three women had reconstruction with implants following bilateral propylactic mastectomy. Approximatelyone‐half of the women (52%) required at least 1 unanticipated reoperation during a median follow‐up of 14 years. Approximately 39% of all reoperations occurred within 1 year of breast reconstruction and 69% within 5 years. Implant‐related issues were the most common cause for reoperation. Some women with breast carcinoma elected to receive contralateral prophylactic mastectomy with therapeutic mastectomy for the affected breast. Five hundred six women received reconstruction with implants. During a median follow‐up of 8.8 years, 189 women (37%) required unanticipated reoperation. The most common indication was implant‐related issues. The time course of reoperations was similar to that for women in the bilateral group.

CONCLUSIONS

Surgical reoperations were fairly common among women who received prophylactic mastectomy with implant reconstruction. Most of the reoperations were implant related. Reoperations were fairly uncommon after prophylactic mastectomy without reconstruction. Cancer 2003. © 2003 American Cancer Society.
The relevance of occult axillary micrometastasis in ductal carcinoma in situ
Authors: Lara Jonathan F. , Young Steven M. , Velilla Rowena E. , Santoro Elissa J. , Templeton Sandra F.
Published: October 2003

BACKGROUND

Ductal carcinoma in situ (DCIS) represents 20% of newly diagnosed breast carcinoma cases. Historically, the incidence of axillary metastasis in DCIS has been small (1–2%) and its significance has been debated. It is widely known that serial sections of lymph nodes coupled with keratin immunohistochemistry (IHC) increases identification of micrometastasis. The advent of sentinel lymph node evaluation underscores the need to reevaluate the significance of occult micrometastases in DCIS.

METHODS

Patients with DCIS and negative axillary lymph nodes from 1974 to 1992 were selected from the Saint Barnabas Medical Center Tumor Registry. All diagnoses were confirmed, and paraffin blocks were retrieved after acceptance into the study. Seven serial sections were obtained from each block and evaluated with two cytokeratin IHC stains. Clinical follow‐up ranged from 10 to 28 years.

RESULTS

One hundred two patients were included in the study. Micrometastases were identified in 13 patients (13%), mostly on 1 level and composed of microscopic clusters in the subcapsular sinus. Seven of these lymph node–positive patients (58%) had high‐grade comedo DCIS, 4 (33%) had intermediate grades of various types of DCIS, and one had a low‐grade micropapillary DCIS. The overall disease recurrence rate was 12%, but micrometasis was not detected in any of the patients who developed disease recurrence.

CONCLUSIONS

Serial IHC evaluation of lymph nodes dramatically increased the identification of occult micrometastasis. However, IHC detected micrometastasis has no apparent clinical significance in DCIS, based on the current long‐term clinicopathologic study. Therefore, the authors questioned the significance of occult micrometastasis, identified by IHC, in DCIS of any type and extent. Further evaluation and follow‐up of lymph node micrometastases in patients with invasive tumors of various sizes are needed. The current findings would not support altering the stage of patients with DCIS and micrometastasis detected by IHC only. Cancer 2003. © 2003 American Cancer Society.
Detection of recurrent oral squamous cell carcinoma by [18F]‐2‐fluorodeoxyglucose‐positron emission tomography
Authors: Kunkel Martin , Förster Gregor J. , Reichert Torsten E. , Jeong Jong‐Hyeon , Benz Peter , Bartenstein Peter , Wagner Wilfried , Whiteside Theresa L.
Published: October 2003

BACKGROUND

Patients with recurrent oral squamous cell carcinoma (OSCC) have a dismal prognosis and represent a therapeutic challenge. A positron emission tomography (PET) scan with [18F]‐2‐fluorodeoxyglucose ([18F]FDG) can improve early cancer detection. The current study evaluates the prognostic value of [18F]FDG‐PET scan in patients with recurrent OSCC.

METHODS

The authors studied 97 patients with previously resected OSCC who were restaged by PET scanning. Of the 97 patients, 64 had no evidence of clinical disease and 33 were suspected of having disease by imaging, clinical findings, or pathologic evaluation. The median follow‐up period was 35.4 months after a PET scan. The end points included disease recurrence, a disease recurrence‐free period 6 months after a PET scan, or death.

RESULTS

The overall sensitivity of a PET scan did not exceed 90% and its specificity varied from 67% for local disease recurrence/second primaries to 99% for lymph node metastasis. Increased [18F]FDG uptake predicted increased hazard of death (hazard ratio: 6.83; P = 0.00034) and proved to be a highly predictive marker of disease status. A significant association was established for incremental standardized uptake values and 3‐year patient survival (P=0.0089), indicating that intense glucose metabolism in the tumor is a negative marker of survival in recurrent OSCC. Overall, survival was longer in patients with a negative rather than a positive PET scan (P < 0.00001).

CONCLUSIONS

PET scanning was found to be highly valuable for diagnosing OSCC recurrence in a postoperative setting. It provided prognostic information and played an important role in patient counseling and management. Cancer 2003. © 2003 American Cancer Society.
Gauging the impact of breast carcinoma screening in terms of tumor size and death rate
Authors: Michaelson James S. , Satija Sameer , Kopans Daniel , Moore Richard , Silverstein Melvin , Comegno Arthur , Hughes Kevin , Taghian Alphonse , Powell Simon , Smith Barbara
Published: October 2003

BACKGROUND

While the question of whether the trials of breast cancer screening have resulted in a reduction in breast cancer death has been the subject of much scrutiny, there has been less attention to the reduction in tumor size achieved by screening.

METHODS

Size data for invasive breast tumors were assembled from a variety of sources. The health consequences that can be expected from finding tumors of various sizes were determined using a recently developed mathematical method for relating tumor size to death rate.

RESULTS

First, in both the Swedish two‐country trial and at the MGH Breast Imaging Division, the sizes of the invasive breast cancers in the screening population (those masses seen at screening together with those found as palpable masses after screening examinations) were sufficiently smaller than the cancers found among women who had not used screening to have lead to considerable reductions in death. Second, the lack of reduction in death rates detected in both Canadian National Breast Screening Studies could be ascribed to the small reductions in tumor size achieved in these studies. Third, radiographic density had a small effect, whereas age had a negligible effect, on the capacity of mammographic screening to find breast carcinomas at smaller, and thus less lethal, sizes.

CONCLUSIONS

Prompt attendance at annual mammographic screening offers the potential to reduce tumor size and, presumably, breast carcinoma death, in women of all ages and density groups. Cancer 2003. © 2003 American Cancer Society.
Prognosis after regional lymph node recurrence in patients with Stage I–II breast carcinoma treated with breast conservation therapy
Authors: Harris Eleanor E. R. , Hwang Wei‐Ting , Seyednejad Farshad , Solin Lawrence J.
Published: October 2003

BACKGROUND

The authors evaluated the risk factors for regional lymph node recurrence and the prognosis of patients with regional nodal recurrence after breast conservation therapy for Stage I–II breast carcinoma.

METHODS

Between 1977 and 1995, 1293 women with pathologic Stage I and II (T1–2, N0–1) breast carcinoma were treated with breast‐conserving therapy including lumpectomy, axillary lymph node dissection, and definitive breast irradiation. A total of 39 women (3%) had any regional lymph node recurrence. The median follow‐up was 8.5 years (range, 1.5–24 years).

RESULTS

Among 39 patients with a regional lymph node recurrence, 10 women had regional recurrence only, 16 had simultaneous locoregional recurrence, and 13 had simultaneous regional and distant recurrence. Regional recurrence occurred in the axillary lymph nodes only (n= 21; 51%), supraclavicular lymph nodes only (n= 8; 23%), internal mammary lymph nodes only (n= 3; 8%), infraclavicular lymph nodes only (n= 3; 8%), or multiple lymph node sites (n= 4; 10%). The median time to regional lymph node recurrence was 3.1 years (range, 0.2–20.9 years). Overall survival after regional‐only disease recurrence was 44%, locoregional disease recurrence was 26%, and regional with distant disease recurrence was 12%. Cause‐specific survival rates at 10 years for the 3 groups were 44%, 40%, and 12%, respectively. For patients who presented with simultaneous regional and distant metastases, the median survival period was 1.1 years, compared with 5.2 years for women who developed distant disease subsequent to regional recurrence.

CONCLUSIONS

Regional lymph node recurrence after breast conservation therapy may be salvaged, but is associated with a high rate of either simultaneous or subsequent distant metastatic dissemination and poor overall prognosis. Cancer 2003. © 2003 American Cancer Society.
Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma
Authors: Geisler John P. , Goodheart Michael J. , Sood Anil K. , Holmes Richard J. , Hatterman‐Zogg Melanie A. , Buller Richard E.
Published: October 2003

BACKGROUND

hMLH1, the human MutL homologue, has been linked to microsatellite instability (MSI) in gastrointestinal tumors. However, to the authors' knowledge, the role of hMLH1, the other mismatch repair genes (MMR), and MSI in ovarian carcinoma has not been well defined. The purpose of the current study was to determine the relation between MSI of ovarian carcinoma and MMR gene expression, hMLH1 and hMSH2 hypermethylation, and hMLH1 and hMSH2 null mutations.

METHODS

hMLH1 mRNA was detected by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and amplification of cDNA using a housekeeping gene (glycerol 3‐phosphate dehydrogenase) as a control for mRNA quality and quantity. Methylation‐specific PCR (MS‐PCR) was used to correlate methylation of the hMLH1 and hMSH2 CpG islands with mRNA expression status. Similar techniques were used to evaluate the concomitant expression of five other MMR: hMSH2, hMSH3, hMSH6, PMS1, and PMS2. Microsatellite instability was studied using the National Cancer Institute consensus markers (D2S123, D5S346, D17S250, BAT25, and BAT26) and NM23 as described previously.

RESULTS

One hundred twenty‐five primary tumors were analyzed. High‐frequency MSI (MSI‐H) was found in 21 tumors (16.8%). hMLH1 mRNA was absent in 10 of these 21 tumors (47.6%). In each case, coordinated hypermethylation of both regions A and C of the promoter was identified. Microsatellite stable and low‐frequency MSI tumors all were found to express not only hMLH1 but the other MMR genes as well (P < 0.001). Absence of expression of hMSH2 and the four other MMRs occurred in tumors with absent hMLH1 mRNA expression because of CpG island hypermethylation. No absence of expression of hMSH2, hMSH3, hMSH6, PMS1, or PMS2 was found to occur in tumors expressing hMLH1. None of the 11 MSI‐H tumors without promoter hypermethylation demonstrated a null mutation in hMLH1 or hMSH2.

CONCLUSIONS

A molecular mechanism to explain > 50% of the MSI‐H phenotype in ovarian carcinoma cases was demonstrated. MSI‐H may occur because of MMR defects, especially hMLH1 promoter hypermethylation. Additional mechanisms are required to explain the balance between the cases of MSI‐H as well as the phenomenon of MSI‐L tumors. Cancer 2003. © 2003 American Cancer Society.
Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high‐grade soft tissue sarcoma
Authors: Morimoto Yuki , Ozaki Toshifumi , Ouchida Mamoru , Umehara Norifumi , Ohata Norihide , Yoshida Aki , Shimizu Kenji , Inoue Hajime
Published: October 2003

BACKGROUND

A recent study revealed that single nucleotide polymorphism (SNP) at codon 388 (Gly or Arg) of fibroblast growth factor receptor 4 (FGFR4) was associated with prognosis in patients with carcinoma of the breast and colorectal carcinoma. The purpose of the current study was to investigate the correlation between codon 388 SNP and clinical prognosis in patients with sarcoma of the bone and soft tissues.

METHODS

Tumor samples were obtained from 143 patients with high‐grade bone and soft tissue sarcomas at Okayama University Hospital between 1986–2002, and from 102 healthy volunteers. SNP of codon 388 was detected by sequencing and fragment length of polymerase chain reaction products digested by restriction enzyme. The chi‐square test was used to compare genotype distribution and the Kaplan–Meier method was used for survival analysis.

RESULTS

With regard to FGFR4 genotypes in the 143 patients studied, 54 (37.8%) were Gly/Gly, 72 (50.3%) were Gly/Arg, and 17 (11.9%) were Arg/Arg, findings that were not significantly different from those of controls (P = 0.97). With regard to cumulative overall and metastasis‐free survival, patients with the Gly/Gly genotype were found to have a better prognosis (P = 0.085 and P = 0.27, respectively). FGFR4 SNP was found to be correlated significantly with overall and metastasis‐free survival in patients with soft tissue sarcomas (P = 0.029 and P = 0.045, respectively), but not in those patients with bone sarcomas (P = 0.88 and P = 0.75, respectively).

CONCLUSIONS

In the current study, the authors found a significant correlation between FGFR4 SNP and prognosis in patients with soft tissue sarcoma, although the samples were comprised of various histologic types. This SNP might be used to improve the prediction of clinical prognosis and lead to new treatment strategies in patients with soft tissue sarcomas. Cancer 2003. © 2003 American Cancer Society.
Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas
Authors: Beckler Andrew D. , Roche James K. , Harper Jeffrey C. , Petroni Gina , Frierson Henry F. , Moskaluk Christopher A. , El‐Rifai Wa'el , Powell Steven M.
Published: October 2003

BACKGROUND

Gastric carcinoma is one of the leading causes of cancer‐related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas.

METHODS

The authors studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real‐time reverse transcriptase‐polymerase chain reaction, and immunohistochemistry.

RESULTS

Strikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified.

CONCLUSIONS

These findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas. Cancer 2003. © 2003 American Cancer Society.
10q25.3 (DMBT1) copy number changes in astrocytoma grades II and IV
Authors: Wessels Peter H. , Twijnstra Albert , Kubat Bela , Ummelen Monique I.J. , Claessen Sandra M.H. , Sciot Raf , Merlo Adrian , Ramaekers Frans C.S. , Speel Ernst J.M. , Hopman Anton H.N.
Published: October 2003

In the literature, it has been suggested that loss of the 10q25‐26 region, including the DMBT1 gene (10q25.3), is correlated with initiation and/or malignant progression of astrocytomas, although the results of the studies on the loss of heterozygosity that led to this assumption are not unequivocal. For this reason, using double‐target fluorescence in situ hybridization, we compared copy number changes of 10q25.3 to those of the pericentromeric region (10q12) in 10 cases each of astrocytoma grades II and IV. The same specimens were analyzed for copy number changes of chromosome 1, as a marker for polyploidy, and chromosome 7, which is often gained in astrocytomas of all grades. Our results show that selective loss of the 10q25.3 region was present in 2 of 10 specimens in both astrocytoma grade II and grade IV, occurring only in tumors with polysomy for 10q12. Furthermore, astrocytoma grade II often showed polyploidy for chromosomes 1, 7, and 10 (8 of 10 specimens). In addition, astrocytoma grade IV frequently exhibited losses of chromosome 10 in a high percentage of nuclei. Although based on a small number of cases, the results clearly show that loss of the 10q25.3 region is uncommon in astrocytoma grade II and mostly coincident with loss of chromosome 10 in grade IV tumors. These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II. © 2003 Wiley‐Liss, Inc.
Two variants of the human hepatocellular carcinoma‐associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B
Authors: Wan Dafang , He Mei , Wang Junru , Qiu Xiaokun , Zhou Wei , Luo Zewei , Chen Jianguo , Gu Jianren
Published: October 2003

We have cloned a cDNA from chromosome band 17p13.3, designated as HCAP1 (HCC‐associated protein 1, originally named HC56). Database searches revealed that HCAP1 shares most of its open reading frame with GEMIN4. Single nucleotide polymorphism (SNP) screening revealed a high incidence of SNP in the coding region of HCAP1 (12 SNP sites). A collection of 140 controls and 22 cases from the Qidong area was genotyped at 6 SNP sites. The 22 cases exhibited higher frequencies of minor alleles than did the controls, and 2 sites revealed significant differences between the controls and the cases. We constructed 2 haplotypes, HCAP1‐N (with common alleles at 5 SNP sites) and HCAP1‐M (with minor alleles at 5 SNP sites), in a mammalian expression system. Both haplotypes resulted in a remarkable reduction in colony formation and suppression of cell growth after being transfected into the human hepatocellular carcinoma (HCC) cell line. The inhibitory effect of HCAP1‐N was stronger than that of HCAP1‐M. Different haplotypes also resulted in different gene expression profiles in the Hep3B cell line according to an examination of 588 genes on an Atlas membrane. The expression induced by HCAP1‐M caused an up‐regulation of genes involved in cellular proliferation and a down‐regulation of genes involved in cellular apoptosis and DNA repair. These results, in addition to the statistical data, are biological evidence that the HCAP1‐M variant of HCAP1 has a reduced inhibitory effect on hepatocarcinoma cell growth and an impaired DNA repair system. This suggests that HCAP1‐M may be related to cancer susceptibility. © 2003 Wiley‐Liss, Inc.
Estimating the marginal value of ‘better’ research output: ‘designed’ versus ‘routine’ data in randomised controlled trials
Authors: Cohen David , Longo Mirella F , Williams John , Cheung Wai‐yee , Hutchings Hayley , Russell I.T.
Published: October 2003

We recently completed a study which demonstrated that the costs of health technology assessment (HTA) by randomised controlled trial (RCT) can be reduced by substituting routine datasets for data designed and collected specifically for a trial. This cost reduction, however, had the effect of reducing the quality of the research output. In the present study we attempted to tease out the values attached to the ‘better’ information provided by designed data RCTs using a mock grants committee. Two valuation techniques, implied values and willingness to pay, were used. Ex ante valuations were determined by comparing alternative research proposals – a more costly version using designed data and a cheaper version using routine data. Ex post valuations were determined by comparing results of both versions. The exercise was performed on four exemplar studies. Overall, the committee expressed a general lack of trust towards routine data both ex ante and ex post and placed high values on the better information from the designed data studies – particularly information on preferences. This suggests that currently available routine datasets are not perceived to be able to provide efficient alternatives to designed data for RCTs. Copyright © 2003 John Wiley & Sons, Ltd.
Metachronous spread of parathyroid carcinoma to a retropharyngeal lymph node
Authors: Rufener Justin B. , Cohen James I.
Published: October 2003

Background.

Parathyroid carcinoma is rare and accounts for approximately 1% of patients with hyperparathyroidism. It is a slowly progressive disease with frequent recurrence and high incidence of local metastasis. Because of the rarity of this tumor, little is known about the pattern of lymph node metastasis.

Methods.

A case of retropharyngeal lymph node metastasis found 2 years after initial diagnosis of parathyroid carcinoma is presented and discussed.

Results.

A 67‐year‐old man initially was seen with asymptomatic hypercalcemia, and a 1.7‐cm mass was removed along with the left hemithyroid. The mass was found to be parathyroid carcinoma. Serum calcium was again elevated 1 year later, and left neck lymph node dissection revealed an upper jugular lymph node containing parathyroid carcinoma. The patient continued to have an elevated serum calcium level, and a retropharyngeal lymph node was found by MRI and removed the following year. The patient is now without evidence of hyperparathyroidism or recurrent disease at 2‐year follow‐up.

Conclusions.

Persistent parathyroid carcinoma is often a clinical challenge because of the difficulty in localizing recurrent tumor. Retropharyngeal lymph nodes should be considered as a possible site of metastasis in patients with parathyroid carcinoma. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Basaloid in contrast to nonbasaloid head and neck squamous cell carcinomas display aberrations especially in cell cycle control genes
Authors: Poetsch Micaela , Lorenz Gerd , Bankau Alexander , Kleist Britta
Published: October 2003

Background.

At present, the differences between head and neck basaloid squamous cell carcinoma (BSCC) and nonbasaloid squamous cell carcinoma (SCC) are mostly on the basis of histologic and immunohistologic findings.

Methods.

In this study, we investigated 8 BSCCs and 59 SCCs for loss of heterozygosity (LOH) at chromosomes 5q, 9p, 9q, 10q, 11q, 13p, 17p, and 18q. In addition, we analyzed p16, PTEN, and CCND1 (cyclin D1) and investigated the HPV status. Immunohistochemically, the expression of MIB‐1, p16, p53, and cyclin D1 was determined.

Results.

Aberrations in the BSCCs were especially frequent at 9p and in the CCND1 gene. In contrast, alterations at 10q occurred almost exclusively in conventional SCCs. Obvious differences could be determined concerning the HPV status: HPV‐DNA was detected in all BSCCs but only in 17% of conventional SCCs.

Conclusions.

Although the number of investigated BSCCs is rather low and did not allow statistical conclusions, our results focus on certain differences between the molecular pathogenesis of BSCCs and SCCs. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Management of neurotropic low‐grade B‐cell lymphoma: Report of two cases
Authors: Garcia‐Serra Allie , Price Mendenhall Nancy , Hinerman Russell W. , Lynch James W. , Braylan Raul C. , Mancuso Anthony A.
Published: October 2003

Background.

Low‐grade lymphomas do not commonly involve the central or peripheral nervous system.

Methods.

Case report and review of the literature of two cases of B‐cell lymphoma of the extranodal marginal zone type involving the head and neck region with evidence of extensive neurotropism are detailed in this report.

Results.

One patient was initially seen with a mass in the temporalis muscle and the other with a masticator space mass. The clinical course was indolent in both cases, although associated imaging studies suggested a more aggressive tumor. Both patients were treated with moderate‐dose radiotherapy only. At the time of writing, one patient has no evidence of disease 6.5 years after treatment and the other at 6 months.

Conclusions.

This suggests that some marginal zone lymphomas exhibit a low‐grade clinical course despite an aggressive radiographic pattern of perineural and neurotropic spread. This type of lymphoma might be effectively treated with moderate‐dose radiotherapy. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Neck level–specific nodal metastases in oropharyngeal cancer: Is there a role for selective neck dissection after definitive radiation therapy?
Authors: Doweck Ilana , Robbins K. Thomas , Mendenhall William M. , Hinerman Russell W. , Morris Christopher , Amdur Robert
Published: October 2003

Purpose.

To determine the extent of the required neck dissection for patients with persistent lymphadenopathy after definitive radiation therapy for oropharyngeal cancer. If feasible, a conservative approach using selective neck dissection would likely minimize the extent of neck fibrosis and other adverse sequelae.

Methods.

Analysis of pretreatment and posttreatment radiologic scans and pathology reports of 76 patients with oropharyngeal carcinoma (35 tonsil; 41 base of tongue), who had radiologic evidence of persistent nodal disease for level‐specific involvement. Patients were treated with twice‐daily fractionations of external‐beam radiation therapy (median dose, 76.8 Gy to the primary tumor) and planned neck dissection (levels I–V) for bulky nodes (N2–3) or salvage neck dissection for N1 disease.

Results.

The distribution of clinical nodal disease by neck level on the basis of pretreatment and posttreatment radiologic scans indicated levels II and III to be most commonly involved. The false‐negative rate for the restaging radiologic scans for each neck level was as follows: level I, 0%; level II, 8%; level III, 6%; level IV, 5%; and level V, 1.5%. Of the eight hemi‐necks found to contain positive pathologic nodes in a neck level judged to be negative on the basis of restaging scans, five of the patients subsequently had disease recurrence in the primary site. Patients who had evidence of residual neck disease had a significantly lower rate of locoregional control (77% vs 100%, p = .0005).

Conclusions.

The extent of neck dissection for patients with nodal disease associated with oropharyngeal cancer treated with radiation therapy should include levels II–IV. It is reasonable to spare levels I and V in patients without radiologic and clinical evidence of positive nodes in levels I and V. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003