Aspiration cytologic, ultrastructural, and DNA cytometric findings of solid and papillary tumor of the pancreas.

Solid and papillary epithelial neoplasm of the pancreas (SPENP) is a rare lesion characteristically occurring in young women. By contrast with pancreatic ductal adenocarcinomas, SPENP is a slow-growing tumor that rarely metastasizes or is fatal. The current report describes light and electron microscopic and histochemical findings with DNA flow cytometric analyses of two cases of SPENP. The first patient was a 24-year-old woman; the second, a 72-year-old man. Although SPENP is rare in older men, both patients had characteristic radiographic and light microscopic features of SPENP. Ultrastructural evidence of acinar differentiation was seen in the first patient; the second patient had focal neuroendocrine differentiation. Flow cytometric analysis of the first tumor demonstrated diploid-range DNA content with a 5.8% S-phase fraction (SPF). The DNA cytometric analysis of a biopsy specimen from the second tumor revealed diploid-range DNA content with a 6.1% SPF, although subsequent sampling of the resected tumor showed an aneuploid population with a DNA index of 1.8 and SPF of 2.1%.     

Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency

A 28-month-old black male died with severe complications of mental and motor deterioration, seizures, and aspiration. Autopsy demonstrated moderate liver enlargement, normal spleen and kidneys, small testes, and a grossly normal brain. Further examination showed irregular macrogyrae with evidence of a storage or sclerotic process. Thin layer chromatography of the lipids in formalin-fixed tissue demonstrated elevated levels of ceramide trihexoside and possibly sulfatides in liver and a decrease in the ratio of galactosylceramide to sulfatide in brain. Examination of the gangliosides in formalin-fixed brain indicated a slight increase in the percentage of GM1 ganglioside and a clear elevation in GM2 and GM3 gangliosides. Cultured skin fibroblasts had a normal activity for a large number of lysosomal enzymes including arylsulfatase A and galactocerebrosidase. When the cells were loaded with [14C]sulfatide only about 12% of the sulfatide was metabolized after 3 days. Extracts of the cells were subjected to SDS-PAGE and immunoblotting with antisphingolipid activator protein-1 (SAP-1) rabbit antiserum, and no cross-reacting material was detected confirming the diagnosis of metachromatic leukodystrophy caused by SAP-1 deficiency. This patient was clinically more severe than the other patients described previously with this deficiency. Further studies are underway to define the nature of the mutation in this patient.     

Plasma levels of enterolactone and percentage mammographic density among postmenopausal women.

AIMS: Certain phytoestrogens, such as lignans, may protect against developing breast cancer. Enterolactone is a lignan metabolite produced by the intestinal flora from dietary precursors such as whole grains, vegetables, and fruits. Enterolactone has been shown to have weak estrogenic and antiestrogenic properties. We decided to examine the association between plasma levels of enterolactone and mammographic density, a biomarker for breast cancer risk. METHODS: We included data from postmenopausal women ages 55 and older who participated in a cross-sectional mammogram study in Troms?, Norway. Mammograms, plasma enterolactone measurements, as well as information on anthropometric and hormonal/reproduction factors were available on 616 women. We assessed mammographic density using a previously validated computer-assisted method. We estimated correlation coefficients and conducted multiple regression analyses. RESULTS: Mean mammographic density increased slightly across quartiles of enterolactone; the women in the highest quartile had, on average, 3.1% (absolute difference) higher percentage mammographic density compared with the lowest quartile (P(trend) < 0.01). After adjustment for age, body mass index, number of full-term pregnancies, age at first birth, and use of postmenopausal hormone therapy, the mean difference in density was reduced to 2.0% (P(trend) = 0.05). Results were similar when restricted to the 454 current hormone nonusers. The fully adjusted statistical model explained 28.3% of the total variability in mammographic percentage density, with body mass index contributing 18.2% and enterolactone only 0.9%. CONCLUSION: In our study, higher levels of enterolactone were associated with slightly higher percentage mammographic density. Our results suggest that if higher enterolactone levels reduce the risk of developing breast cancer in postmenopausal women, then this effect is not through lowering mammographic density.     

Integration of light scattering with machine learning for label free cell detection

Light scattering has been used for label-free cell detection. The angular light scattering patterns from the cells are unique to them based on the cell size, nucleus size, number of mitochondria, and cell surface roughness. The patterns collected from the cells can then be classified based on different image characteristics. We have also developed a machine learning (ML) method to classify these cell light scattering patterns. As a case study we have used this light scattering technique integrated with the machine learning to analyze staurosporine-treated SH-SY5Y neuroblastoma cells and compare them to non-treated control cells. Experimental results show that the ML technique can provide a classification accuracy (treated versus non-treated) of over 90%. The predicted percentage of the treated cells in a mixed solution is within 5% of the reference (ground-truth) value and the technique has the potential to be a viable method for real-time detection and diagnosis.     

Anti-melanoma antibodies from melanoma patients immunized with genetically modified autologous tumor cells: selection of specific antibodies from single-chain Fv fusion phage libraries.

Fusion phage libraries expressing single-chain Fv antibodies were constructed from the peripheral blood lymphocytes of two melanoma patients who had been immunized with autologous melanoma cells transduced the gamma-interferon gene to enhance immunogenicity, in a trial conducted at another institution. Anti-melanoma antibodies were selected from each library by panning the phage against live cultures of the autologous tumor. After two or three rounds of panning, clones of the phage were tested by ELISA for binding to the autologous tumor cells; > 90% of the clones tested showed a strong ELISA reaction, demonstrating the effectiveness of the panning procedure for selecting antimelanoma antibodies. The panned phage population was extensively absorbed against normal melanocytes to enrich for antibodies that react with melanoma cells but not with melanocytes. The unabsorbed phage were cloned, and the specificities of the expressed antibodies were individually tested by ELISA with a panel of cultured human cells. The first tests were done with normal endothelial and fibroblast cells to identify antibodies that do not react, or react weakly, with two normal cell types, indicating some degree of specificity for melanoma cells. The proportion of phage clones expressing such antibodies was approximately 1%. Those phage were further tested by ELISA with melanocytes, several melanoma lines, and eight other tumor lines, including a glioma line derived from glial cells that share a common lineage with melanocytes. The ELISA tests identified three classes of anti-melanoma antibodies, as follows: (i) a melanoma-specific class that reacts almost exclusively with the melanoma lines; (ii) a tumor-specific class that reacts with melanoma and other tumor lines but does not react with the normal melanocyte, endothelial and fibroblast cells; and (iii) a lineage-specific class that reacts with the melanoma lines, melanocytes, and the glioma line but does not react with the other lines. These are rare classes from the immunized patients' repertoires of anti-melanoma antibodies, most of which are relatively nonspecific anti-self antibodies. The melanoma-specific class was isolated from one patient, and the lineage-specific class was isolated from the other patient, indicating that different patients can have markedly different responses to the same immunization protocol. The procedures described here can be used to screen the antibody repertoire of any person with cancer, providing access to an enormous untapped pool of human monoclonal anti-tumor antibodies with clinical and research potential.     

Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

BACKGROUND: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery. METHODS: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded. RESULTS: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics. CONCLUSIONS: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.