The new partnership of genomics and chemistry for accelerated drug development

The Grashey shoulder position is used to demonstrate damage to the glenohumeral joint caused by osteoarthritis, sclerosis, tumors, fractures, osteophytes and cystic changes. However, it can be difficult to assess loss of articular cartilage using the Grashey shoulder position because little axial load is applied to the glenohumeral joint. This article describes a method of creating a loading force across the glenohumeral joint by adding weighted arm abduction during the Grashey position to demonstrate loss of the articular cartilage. Case studies and radiographs are presented to discuss the advantages of using the Grashey position with weighted abduction.     

Monolithic rat-race mixers for millimeter waves

In this paper, we report on fully monolithic millimeter-wave Schottky-barrier diode (SBD) down-converters with an IF amplifier using heterojunction bipolar transistors (HBT's). A rat-race circuit is used for the mixer, and is analyzed using a harmonic-balance simulator. The measured conversion gain and the isolation are 7.1 and 29 dB in the V-band design, and 8.0 and 25 dB in the W-band design, respectively. The conversion gains are matched well with the circuit simulation     

Identification of K1/K10 and K5/K14 keratin pairs in human melanoma cell lines

Keratin expression in cultured malignant melanoma cells has been studied only rarely. Moreover, no studies have reported of universality of keratin expression in human malignant melanoma cells. In this study, therefore, we analyzed keratin expression in eight cell lines. Using a low-salt aqueous solution without high salt and Triton X-100, as a washing buffer for keratin extraction, followed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and immunological analysis, we demonstrated keratin expression in all eight human malignant melanoma cell lines. The keratin polypeptide expressions common to all melanoma cells were K1, K5, K10 and K14. In addition, K8, K13, K17 and K18, respectively, were detected in individual cells. A measure of keratin expression universality in malignant melanoma cells may have implications regarding their invasive and metastatic behaviors, co-expressed with vimentin.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer

OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced to detect malignancy in an early and curable stage. However, the cost-effectiveness of this practice has been questioned. To clarify this issue, we undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in Barrett's esophagus compared with mammography used to detect occult carcinoma of the breast, a widely accepted cancer surveillance technique. METHODS: The rate of esophageal adenocarcinoma detected by endoscopic surveillance was calculated for Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and compared with published rates. The rate of occult breast cancer detection was calculated for all women undergoing surveillance mammography at the Duluth Clinic for the year 1994 and compared with published rates. Costs for screening studies and therapy for cancer treatment for both cancers were calculated based on clinical results and assumptions regarding outcomes derived from published reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149 patients with benign Barrett's esophagus was performed for a total of 510 patient-yr, during which time seven patients developed adenocarcinoma, an incidence of one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50 of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were comparable to published figures. The costs of detecting a case of adenocarcinoma in Barrett's esophagus and occult breast cancer were $37,928 and $54,513, respectively, and those for treatment resulting in cure were $83,340 and $83,292. Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with Barrett's esophagus compares favorably with the common practice of surveillance mammography to detect early breast cancer, and should therefore be considered to be as cost-effective as surveillance mammography.     

Bone and calcium metabolism in Werner''s syndrome

Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis (PCM), was first isolated from armadillos from the Amazonian region where the mycosis is uncommon. In the present study, we report on the high incidence of PCM infection in armadillos from a hyperendemic region of the disease. Four nine-banded armadillos (Dasypus novemcinctus) were captured in the endemic area of Botucatu, Sao Paulo, Brazil, killed by manual cervical dislocation and autopsied under sterile conditions. Fragments of lung, spleen, liver, and mesenteric lymph nodes were processed for histology, cultured on Mycosel agar at 37 degrees C, and homogenized for inoculation into the testis and peritoneum of hamsters. The animals were killed from week 6 to week 20 postinoculation and fragments of liver, lung, spleen, testis, and lymph nodes were cultured on brain heart infusion agar at 37 degrees C. Paracoccidioides brasiliensis was isolated from three armadillos both by direct organ culture and from the liver, spleen, lung, and mesenteric lymph nodes of hamsters. In addition, one positive armadillo presented histologically proven PCM disease in a mesenteric lymph node. The three armadillos isolates (Pb-A1, Pb-A2, and Pb-A4) presented thermodependent dimorphism, urease activity, and casein assimilation, showed amplification of the gp43 gene, and were highly virulent in intratesticularly inoculated hamsters. The isolates expressed the gp43 glycoprotein, the immunodominant antigen of the fungus, and reacted with a pool of sera from PCM patients. Taken together, the present data confirm that armadillos are a natural reservoir of P. brasiliensis and demonstrate that the animal is a sylvan host to the fungus.     

The Gmicro/500 superscalar microprocessor with branch buffers

The Gmicro/500, which features a RISC-like dual-pipeline structure for high-speed execution of basic instructions and represents a significant advance for the TRON architecture, is presented. Upwardly-object-compatible with earlier members of the Gmicro series, this microprocessor uses resident dedicated branch buffers to greatly enhance branch instruction execution speed. Its microprograms simultaneously use dual execution blocks to execute high-level language instructions effectively. Fabricated with a 0.6-μm CMOS technology on a 10.9-mm×16-mm die, the chip operates at 50/66 MHz and achieves a processing rate of 100/132 MIPS     

Determination of the in situ forces and force distribution within the human anterior cruciate ligament

The in situ forces and their distribution within the human anterior cruciate ligament (ACL) can clarify this ligament's role in the knee and help to resolve controversies regarding surgical treatment of ACL deficiency. We used a universal force-moment sensor (UFS) to determine the magnitude, direction, and point of application of the in situ forces in the ACL in intact human cadaveric knees. Unlike previous studies, this approach does not require surgical intervention, the attachment of mechanical devices to or near the ACL, or a priori assumptions about the direction of in situ force. Anterior tibial loads were applied to intact knees, which were limited to 1 degree of freedom at 30 degrees flexion. The in situ forces developed in the ACL were lower than the applied force for loads under 80 N, but larger for applied loads of more than 80 N. The direction of the force vector corresponded to that of the anteromedial (AM) portion of the ACL insertion on the tibial plateau. The point of force application was located in the posterior section of the anteromedial portion of the tibial insertion site. The anterior and posterior aspects of the anteromedial portion of the ACL supported 25% and 70% of the in situ force, respectively, with the remainder carried by the posterolateral portion. We believe that the data obtained with this new UFS methodology improves our understanding of the role of the ACL in knee function, and that this methodology can be easily extended to study the function of other ligaments.