Developmental stability in stocks of White Leghorn chickens

The degree of asymmetry in bilateral morphological characters may reflect genetic and environmental stressors. Shank length and diameter, weight and length of the first primary wing feather, and distance between the junction of upper and lower mandibles and auditory canal (face length) were used to classify bilateral types and measure relative asymmetry (RA) in six genetic stocks. The stocks were the S23 generation of White Leghorn lines selected for high or low antibody response to SRBC, sublines in which selection had been relaxed for eight generations, and reciprocal crosses of the selected lines. Differences were found among all stocks for the traits measured. Rankings among traits for RA in descending order were face length, shank diameter, feather weight, and shank and feather lengths. The RA of shank and feather lengths did not differ from each other. An overall RA composed of mean RA of the five traits showed that the two selected lines exhibited greater RA than the crosses between them. The RA of the two lines where selection had been relaxed was similar to that of selected lines. This research suggests that an overall RA created as a combination of RA of several bilateral traits can be a valid measure of genetic stress in chickens and provides a method of comparing developmental stability among populations.     

Neural navigation interfaces for Information Retrieval: Are they more than an appealing idea?

Neural networks have recently been proposed for the construction of navigation interfaces for Information Retrieval systems. In this paper, we give an overview of some current research in this area. Most of the cited approaches use (variants) of the well-known Kohonen network. The Kohonen network implements a topology-preserving dimensionality-reducing mapping, which can be applied for information visualization. We identify a number of problems in the application of Kohonen networks for Information Retrieval, most notably scalability, reliability and retrieval effectiveness. To solve these problems we propose to use the Growing Cell Structures network, a variant of the Kohonen network which shows a more flexible adaptation to the domain structure.This network was tested on two standard test-collections, using a combined recall and precision measure, and compared to traditional IR methods such as the Vector Space Model and various clustering algorithms. The network performs at a competitive level of effectiveness, and is suitable for visualization purposes. However, the incremental training procedures for the networks result in a reliability problem, and the approach is computationally intensive. Also, the utility of the resulting maps for navigation will need further improvement.     

PET in breast cancer

In mid-summer 1997, just as the United States National Cancer Institute was acknowledging that the nuclear bomb tests at the Nevada Test Site may ultimately cause up to 75,000 cases of thyroid cancer in people who were living in the USA in the 1950s and 1960s, the Australian authorities were mooting the possibility that the Maralinga test sites in South Australia should become a tourist attraction. Some Aboriginal tribal leaders welcomed this proposed use when the 20 million Pounds 'clean-up' being paid for by the United Kingdom government as some compensation for using the area for its weapons tests in the 1950s and 1960s is completed. This paper surveys the attempts to clean up the site of UK nuclear weapons tests in the 1950s, not least by attempting to vitrify vast tracts of desert.     

Oligoclonal protein bands and Ig isotype switching in multiple myeloma treated with high-dose therapy and hematopoietic cell transplantation

Multiple myeloma (MM) is usually characterized by production of a single serum monoclonal protein of constant isotype and light-chain restriction. Multiple Ig isotypes and isotype switches, which are rare in untreated patients, are reported to be more common in patients undergoing myeloablative therapy. These additional protein bands, detected by immunofixation electrophoresis (IFE), could be due to altered paraprotein production by the malignant plasma cell clone or oligoclonal Ig production during recovery of B-cell function after myeloablative therapy. We analyzed abnormal protein bands (APB), distinct from the presenting paraprotein, in 550 patients receiving high-dose therapy with autologous hematopoietic cell transplantation at a single institution. Fifty-five patients (10%) had APB, 48 had oligoclonal bands (OB), and 23 had an apparent isotype switch (IS) on IFE (16 had both OB and IS). Morphologic and flow cytometric examination of bone marrow in 17 patients with IS showed no evidence of a clonal plasma cell isotype switch. Patients with APB had significantly higher complete response to therapy (67% v 37%, P = .001). To assess the independent prognostic relevance of APB, a multivariate analysis was performed among 471 patients surviving at least 12 months from first transplant (all patients developing APB had done so by 12 months from first transplant). APB (in 50 patients) was a favorable feature for both event-free (rank 3, P = .004) and overall survival (rank 3, P = .0005). We propose that OB and IS are likely to be due to recovery of Ig production rather than alterations in the biology of the malignant plasma cell clone.     

Hematocrit values in weight-selected and relaxed lines of White Rock chickens

Hematocrits (PCV) were measured at 29 and 106 d of age (PCV1 and PCV2, respectively) in male and female White Plymouth Rocks. Four lines were used, two of which had undergone 40 generations of divergent selection for 8-wk BW (HWS, LWS), and two respective sublines (HWR, LWR), in which selection had been relaxed for five generations. At both ages, males and females did not differ for PCV in lines HWR, LWR, and LWS. For line HWS there was an age by sex interaction that resulted from an age effect for males but not for females, and from a sex effect at each age. At both ages, PCV was higher for the HW than the LW lines. Initially, there was no difference between the selected and their respective relaxed lines, but by 106 d, HWR chickens had a higher PCV than HWS chickens. In lines HWR and LWR, PCV increased with age. There was a negative correlation in HWS males for PCV1 with 28 and 56 d BW. The HWR males also had a negative correlation for PCV1 with BW at 28 d, but not between PCV2 and BW. The correlation for PCV1 with PCV2 was high and positive for HWR males and females.     

Measurements on a 215-GHz subharmonically pumped waveguide mixerusing planar back-to-back air-bridge Schottky diodes

This paper presents design and performance data for a 215-GHz subharmonically pumped waveguide mixer using an antiparallel-pair of planar air-bridge-type GaAs Schottky-barrier diodes. The waveguide design is a prototype for a 640-GHz system and uses split-block rectangular waveguide with a 2:1 width-to-height ratio throughout. The measured mixer noise and conversion loss are below that of the best reported whisker contacted or planar-diode mixers using the subharmonic-pump configuration at this frequency. In addition, the required local oscillator power is as low as 3 mW for the unbiased diode pair, and greater than 34 dB of LO noise suppression is observed. Separate sideband calibration, using a Fabry-Perot filter, indicates that the mixer can be tuned for true double sideband response at an intermediate frequency of 1.5 GHz. Microwave scale model measurements of the waveguide mount impedances are combined with a mixer nonlinear analysis computer program to predict the mixer performance as a function of anode diameter, anode finger inductance, and pad-to-pad fringing capacitance. The computed results are in qualitative agreement with measurements, and indicate that careful optimization of all three diode parameters is necessary to significantly improve the mixer performance     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Temporal aspects of the effects of cooling on responses of single auditory nerve fibers

During an investigation of the effects of cochlear cooling on frequency tuning and input/output relations of single auditory nerve fibers in gerbil (Ohlemiller and Siegel (1994) Hear. Res. 80, 174-190), cooling-related changes in post-stimulus time histogram (PSTH) shape and phase-locking to tonebursts were characterized in a small sample of neurons. Local cochlear cooling by 5-10 degrees C below normal core temperature did not alter overall PSTH shape, although some evidence was found for a reduction in the time constants of rapid and short term rate adaptation. The relative contributions of rapid and short term response components appeared unaltered. Effects of cooling on phase-locking were assessed by calculating the synchronization index for responses to intense ( > 70 dB SPL) tonebursts at 0.5, 1.0, and 2.0 kHz. Synchronization filter functions exhibited modest reductions in both magnitude and the upper frequency limit of phase-locking. The effects of cooling on the temporal character of responses appear distinct from those of a simple reduction in stimulus intensity. Results are interpreted in terms of cooling-related changes in responses of cochlear hair cells and afferent neurons, and suggest that temperature artifacts are unlikely to underlie reported species differences in PSTH shape and phase-locking.     

Positron emission tomography with 2-[18F]Fluoro-2-deoxy-D-glucose and 16alpha-[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy

We assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and 16alpha-[18F]fluoro-17beta-estradiol (FES) in women with breast cancer for predicting response to systemic therapy. Results of FES-PET were correlated with estrogen receptor (ER) status. Forty-three women with locally advanced or metastatic breast cancer underwent FDG-PET and FES-PET prior to institution of systemic therapy. All patients had measurable disease and had tumors submitted for ER determination. Cancers were considered functionally hormone sensitive if the standardized uptake value of the lesion on FES-PET was >/=1.0 (FES+) and hormone resistant if the standardized uptake value was <1.0 (FES-). Information obtained by FES-PET was compared with the results of ER assays. The tumor response to chemotherapy and hormonal therapy was correlated with intensity of uptake by both FDG-PET and FES-PET. The ER status of the breast cancers was negative (ER-) in 20 patients, positive (ER+) in 21 patients, and unknown in 2 patients. All 20 of the ER- tumors were also FES-. However, of the 21 ER+ tumors, 16 were FES+ and 5 were FES-. Thirty patients were treated initially with chemotherapy, and 21 (70%) demonstrated objective responses. We were unable to correlate the response to chemotherapy with information obtained by FDG-PET or FES-PET. Thirteen patients were treated with hormone therapy, and 8 (61%) responded to that therapy. Only 1 of the 5 patients whose tumors were ER+ but FES- received hormone therapy, and this treatment resulted in disease stabilization only. Multiple sites of disease were assessed by FES-PET in 17 patients with metastatic breast cancer. Functional hormone sensitivity, defined by FES-PET, was concordant with multiple lesions in 13 (76%). Ten patients with locally advanced breast cancer developed recurrent disease. The initial site of recurrence was the breast in 5 patients. Of the 5 patients with systemic recurrence, 4 had disease detected at the site of recurrence on the pretreatment FDG-PET study but not detected on pretreatment computed tomography. In our experience, FDG-PET imaging is more sensitive than conventional imaging methods, including computed tomography, in staging women with breast cancer. When compared with the in vitro assay of ER status, FES-PET has an apparent sensitivity of 76% and specificity of 100%. Our finding of a subset of patients who have tumors that are ER+ and FES- suggests that the functional assessment of hormone sensitivity by PET imaging can identify patients with ER+ disease whose tumors are likely to be hormone refractory.     

Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer

Neu (c-erbB2) is a proto-oncogene product that encodes an epidermal growth factor-like receptor tyrosine kinase. Amplification of wild-type c-Neu and mutational activation of Neu (Neu T) have been implicated in oncogenic transformation of cultured fibroblasts and mammary tumorigenesis in vivo. Here, we examine the relationship between Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Recent studies have suggested that caveolins may function as negative regulators of signal transduction. Our current results show that mutational activation of c-Neu down-regulates caveolin-1 protein expression, but not caveolin-2, in cultured NIH 3T3 and Rat 1 cells. Conversely, recombinant overexpression of caveolin-1 blocks Neu-mediated signal transduction in vivo. These results suggest a reciprocal relationship between c-Neu tyrosine kinase activity and caveolin-1 protein expression. We next analyzed a variety of caveolin-1 deletion mutants to map this caveolin-1-dependent inhibitory activity to a given region of the caveolin-1 molecule. Results from this mutational analysis show that this functional in vivo inhibitory activity is contained within caveolin-1 residues 32-95. In accordance with these in vivo studies, a 20-amino acid peptide derived from this region (the caveolin-1 scaffolding domain) was sufficient to inhibit Neu autophosphorylation in an in vitro kinase assay. To further confirm or refute the relevance of our findings in vivo, we next examined the expression levels of caveolin-1 in mammary tumors derived from c-Neu transgenic mice. Our results indicate that dramatic reduction of caveolin-1 expression occurs in mammary tumors derived from c-Neu-expressing transgenic mice and other transgenic mice expressing downstream effectors of Neu-mediated signal transduction, such as Src and Ras. Taken together, our data suggest that a novel form of reciprocal negative regulation exists between c-Neu and caveolin-1.