Biomedical subjects

B E Miller

Publications and source records attributed to B E Miller.

At least 55 records · Page 3Linked to original sources

PubMed1995

Successful application of the Norwood procedure for infants without hypoplastic left heart syndrome.

Although the first-stage Norwood procedure mostly has been used for hypoplastic left heart syndrome, there are other anomalies in which the Norwood procedure can be applied. Since 1991, 18 newborns without hypoplastic left heart syndrome underwent a first-stage Norwood procedure. All had a hypoplastic aortic annulus, ascending aorta, and transverse aorta. Ten had normally related great arteries: aortic atresia or aortic stenosis with inadequate left ventricle in 4, mitral atresia or stenosis in 4, and interrupted aortic arch in 2. The 8 others had double-outlet right ventricle with mitral atresia or complete transposition with a hypoplastic right ventricle. Age ranged from 2 to 77 days (median, 6 days) and weight from 2.4 to 4.4 kg (mean, 3.0 kg). The patients with interrupted aortic arch simultaneously underwent primary repair of the interruption. There were 17 hospital survivors (94%). There have been no late deaths in follow-up from 4 to 30 months (mean, 15.5 months). Thirteen children have had subsequent creation of a bidirectional Glenn shunt with takedown of the original systemic to pulmonary shunt. The 2 with interrupted aortic arch underwent a Rastelli-type biventricular repair. These results show that the Norwood procedure can be applied to infants without hypoplastic left heart syndrome who have hypoplastic aortas and excessive pulmonary blood flow with very low mortality and excellent palliation.

Aorta↗

PubMed1995

Association of Chlamydia trachomatis immunoglobulin gamma titers with dystrophic peritoneal calcification, psammoma bodies, adhesions, and hydrosalpinges.

OBJECTIVE: To correlate Chlamydia trachomatis immunoglobulin gamma (IgG) titers with psammoma bodies, dystrophic peritoneal calcification, degree of calcification, adhesions, and hydrosalpinges. DESIGN: This is a prospective single-blinded histologic analysis of tissue and retrospective analysis of historical laboratory and clinical variables. SETTING: Tertiary hospital and private practice patient charts. PATIENTS: Sixty consecutive patients with C. trachomatis IgG titers reported on the coding sheets of a previous study for endometriosis. MAIN OUTCOME MEASURES: The histologic slides were reviewed in a blinded fashion for calcification. Previously used data sheets were reviewed for C. trachomatis IgG titers. Historical data, adhesion scores, hystrosalpingogram findings, and laparoscopic findings were obtained from charts. RESULTS: Dystrophic calcification, psammoma bodies, moderate-to-severe dystrophic calcification and hydrosalpinges were associated with positive C. trachomatis IgG titers. CONCLUSION: This study suggests relationship of C. trachomatis with dystrophic calcification, psammoma bodies, adhesions, and hydrosalpinges. This relationship suggests that C. trachomatis IgG titers can be used as a marker to help determine those infertility patients who might best benefit from hysterosalpingogram or laparoscopy and in clinical studies of endometriosis, infertility, pain, or ovarian cancer. However, there is no current data to suggest a need for therapy on the basis of a positive C. trachomatis IgG titer or of dystrophic peritoneal calcification.

Body Fluids↗

PubMed1994

Enhanced metastatic ability of TNF-alpha-treated malignant melanoma cells is reduced by intercellular adhesion molecule-1 (ICAM-1, CD54) antisense oligonucleotides.

Treating human malignant melanoma cells with tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) causes a dose- and time-dependent increase in surface expression of ICAM-1. Increased ICAM-1 expression corresponds to greater binding of human leukocyte functional antigen-1 (CD11a/CD18)-expressing peripheral blood mononuclear cells (PBMC) to C8161 monolayers, suggesting that cytokine-treated melanoma cells would be more metastatic due to PBMC-tumor cell emboli. The purpose of this study was: (1) to test whether TNF-alpha-treated human melanoma cells are indeed more metastatic than untreated C8161 and (2) to determine whether ICAM-1 plays a role in metastasis of C8161. When surface ICAM-1 expression is upregulated, formation of lung metastases in nude mice increases 1.5- to 4-fold (P < 0.05) for human melanoma cell lines C8161, MeWo, and A375. Treatment of C8161 with ICAM-1 phosphorothioate antisense oligonucleotides using cationic lipids results in > 90% inhibition of ICAM-1 surface expression as determined by ELISA and flow cytometry. Antisense ICAM-1-treated cells form 41-64% fewer metastases than sham-treated cells. Metastasis does not increase when antisense-treated melanoma cells are exposed to TNF-alpha. However, treatment of C8161 with antisense 5-lipoxygenase (5-LO) oligonucleotides inhibits metastases 39% in Lipofectin-treated cells, but does not inhibit TNF-alpha-induced upregulation of experimental metastases. Similar experiments were performed to measure PBMC adhesion to antisense oligonucleotide-treated C8161 cells; however, TNF-alpha-inducible increase in adhesion was unaffected by ICAM-1 or 5-LO antisense oligonucleotides. These results demonstrate that ICAM-1 is involved in melanoma metastasis, but probably not at the step of PBMC adhesion to C8161 cells.

Animals↗

PubMed1994

Quantification of skeletal alkaline phosphatase in osteoporotic serum by wheat germ agglutinin precipitation, heat inactivation, and a two-site immunoradiometric assay.

Three methods for quantifying skeletal alkaline phosphatase (ALP; EC 3.1.3.1) activity/immunoactivity in serum--heat inactivation, wheat germ agglutinin (WGA) precipitation, and an immunoradiometric assay--were tested for recovery and specificity and applied to 81 sera collected from 14 postmenopausal osteoporotic subjects. The heat-inactivation and WGA precipitation assays showed relative recoveries of 91-100% and 16-32%, respectively, for skeletal ALP with complete specificity (no cross-reactivity with hepatic or intestinal ALP); the IRMA showed a relative recovery of 86-100% and 11-14% cross-reactivity with hepatic ALP. There was a closer correlation between the heat-inactivation assay and IRMA (r = 0.833) than between the WGA precipitation assay and IRMA (r = 0.673) or between the heat-inactivation and WGA-precipitation assays (r = 0.568). The WGA precipitation assay failed to detect skeletal ALP in three serum samples that contained significant amounts as determined by the heat-inactivation assay and the IRMA.

Alkaline Phosphatase↗

PubMed1994

Glutamate receptor gene expression in spinal cord of arthritic rats.

Injury to peripheral tissue leads to hyperalgesia that appears to be partly mediated by functional changes at the level of the spinal cord. Glutamate receptors are thought to play a role in acute and short-term (minutes to hours) spinal cord nociceptive responses and may be involved in prolonged or chronic pain (hours to days). We used in situ hybridization to examine AMPA/kainate (GluR1, GluR2, and GluR3) and NMDA (NR1) receptor gene expression in spinal cord following induction of prolonged inflammation by a unilateral intraarticular injection of lipopolysaccharide (LPS; 10 micrograms) into the hindpaw. In control rats, GluR1 expression was prominent throughout the layers of the gray matter of the spinal cord. Microscopic examination revealed labeling of neuronal cell somata in all major nuclei. GluR2 was abundant in substantia gelatinosa and motor nuclei; emulsion-dipped sections exhibited intense labeling over densely packed neurons in the superficial laminae of dorsal horn and individual motoneurons of ventral horn. GluR3 and NR1 were expressed at low levels throughout spinal cord gray matter. One day after LPS injection, when joint swelling was maximal, GluR1 expression was bilaterally decreased by 25% in the substantia gelatinosa at the level of the lumbar cord. In contrast, no significant change was apparent in GluR2, GluR3, or NR1 expression in any nucleus of the cord. At 72 hr after injection, when joint diameter approached control values, all four transcripts were expressed at near control levels. These findings provide evidence for a specific decrease in GluR1 expression in the cord in response to joint inflammation.

Animals↗

PubMed1993

The presentation of adenocarcinoma of the uterine cervix.

BACKGROUND: Among malignancies of the uterine cervix, the percentage of adenocarcinomas seems to have increased in recent reports. METHODS: The clinical presentation of adenocarcinoma of the uterine cervix during the past 25 years was examined by review of charts and pathologic specimens. The data of a total of 124 patients with cervical adenocarcinoma treated between 1964 and 1988 were evaluated. RESULTS: During the 25-year period, the percentage of adenocarcinoma among all cervical malignancies increased from 9% to 25%. In addition, the average number of new cases per year increased from 3.7 to 10.8. The percentage of women young than 35 years with adenocarcinoma increased from 16% in 1964 to 24% in 1989. Of these younger women, 74% had disease discovered by cytopathology, in comparison with 27% of the patients who were older than 35 years. The overall percentage of patients with disease diagnosed by cytology increased from 24% in the first half to 39% in the second half of the study period. Vaginal bleeding was the most common symptom. In the entire period, 57% of patients had International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, with a median tumor diameter of 1 cm in patients with no symptoms and 3 cm in patients with symptoms. Outcome was inversely related to stage, tumor volume, and the presence of lymph node metastasis but not to histologic tumor type. CONCLUSION: The frequency of adenocarcinoma of uterine cervix is increasing in patients 35 years or younger. Cytopathology is a good screening tool for these patients, leading to earlier diagnosis and improved outcome.

Adenocarcinoma↗

PubMed1993

Phosphorylated tau epitope of Alzheimer's disease is coupled to axon development in the avian central nervous system.

The monoclonal antibody PHF-1 recognizes phosphorylated tau isoforms present in paired helical filaments of Alzheimer's disease. We have found that PHF-1 immunoreactivity is present in chick brain, which expresses three major PHF-1-reactive proteins at the same molecular weights seen in humans. The developmental pattern of expression suggests a functional role in differentiation, rather than in programmed nerve cell death. Expression of PHF-1 immunoreactivity in developing retina was highly cell selective, showing robust staining of ganglion cells, the only long-axon neuron of the seven major retina cell types. The majority of ganglion cells were PHF-1 positive. The developmental window of expression extended at least from E6 through P0, well outside the period of embryonic ganglion cell death. Mature cells did not show PHF-1 immunoreactivity. In the embryo, staining was particularly robust in ganglion cell axons (optic fiber layer), and association of PHF-1 reactivity with axonal tracts also was seen in developing forebrain. PHF-1 polarization occurred at ages when staining with polyclonal anti-tau did not show axonal selectivity. Similarly, in cell cultures, PHF-1 immunoreactivity became localized to single neurites, but polyclonal anti-tau did not. These results indicate that, rather than being associated with cell degeneration, PHF-1 immunoreactivity in the developing nervous system is associated with early stages of axon formation, both in vivo and in vitro. Therefore, expression of PHF-1 immunoreactive proteins in Alzheimer's disease suggests that paired helical filament formation might be triggered by mechanisms related to axon regeneration.

Alzheimer Disease↗

PubMed1993

Melphalan sensitivity as a function of progressive metastatic growth in two subpopulations of a mouse mammary tumour.

In order to examine in detail the sensitivity to chemotherapy of tumour cells at various organ sites and at various stages of metastasis, we have used a series of cell lines, all selected from sister subpopulations derived from a single mouse mammary tumour, which can be distinguished and quantitated from normal cells and from each other through growth in selective medium. For the studies described here, we used two lines, 4T07 and 66FAR, which will form colonies in vitro in medium containing 60 microM 6-thioguanine or 330 microM 2,6-diaminopurine, respectively. Both cell lines have similar sensitivity to the test chemotherapeutic agent, melphalan, in vitro. These two tumour cell lines were treated with melphalan in vivo, when growing either in lungs as experimental metastases at various times after cell injection or as palpable tumours growing subcutaneously. Responses to various doses of melphalan were measured by removing lungs or subcutaneous tumours and performing colony-forming assays in selective medium. The data indicate marked shifts in sensitivity as a function of metastatic stage. Analyses of dose-response curves show that both cell lines were similarly sensitive to melphalan at early times (45 min) after cell injection i.v. but became less sensitive at an intermediate time after injection (3 days). Differences between the two lines became apparent at later times after i.v. injection (by day 8 or 9) and in subcutaneous tumours, where a marked reduction in the shoulder of the dose response curve was seen in line 4T07, resulting in sensitivity equal to or greater than the of early times, whereas the dose response parameters of 66FAR remained at those of the intermediate time point. These results show that, in heterogeneous tumours, individual subpopulations of tumour cells may respond differently to chemotherapeutic agents at various disease stages. In vitro measures of tumour sensitivity do not predict these changes in in vivo sensitivity. Model systems similar to the one described here may yield information which will eventually be useful in maximising the efficacy of clinically relevant adjuvant chemotherapy regimens.

Animals↗

PubMed1993

Confocal laser scanning immunofluorescence microscopy of the pulmonary surfactant system. Association of surfactant protein A with the nucleus of the alveolar type II cell.

BACKGROUND: Localization of surfactant protein A (SP-A) to nucleus of type II cells isolated from the lungs of rats has been reported. Data suggested that most SP-A was located within lamellar bodies of the type II cell; however, some SP-A was found in other cytoplasmic regions of the cell and in particular in the nucleus. EXPERIMENTAL DESIGN: Type II cells and type II cell nuclei isolated from the lungs of rats were reacted with affinity-purified antibodies against SP-A. Location of SP-A was determined by using fluorescein isothiocyanate-labeled secondary antibodies and the distribution of fluorescence examined by using a laser scanning microscope fitted with a confocal aperture. Two-dimensional electrophoresis followed by Western blotting was used to separate and identify type II cell nuclear proteins. RESULTS: Nuclei were isolated from type II cells obtained from elastase-digested rat lungs and examined for the presence of SP-A. The nuclei contained both focal and diffuse deposits of SP-A. Some regions within the nuclear matrix (in particular the nucleolus) appeared to be relatively devoid of SP-A. The perinuclear membrane stained intensely for SP-A where optical sectioning showed its presence as a patchwork of punctate deposits. Analysis of the SP-A associated with the nucleus by two-dimensional electrophoresis revealed that it consisted of a family of proteins with molecular masses of 26, 32, and 36 kDa and pI 5.1. Biosynthesis of nuclear SP-A in primary cultures of type II cells was sensitive to inhibitors of glycosylation resulting in the presence of only the lowest molecular weight unprocessed form. CONCLUSIONS: These data indicate that three basic forms of SP-A are associated with the nucleus of the type II cell and are especially concentrated on the perinuclear membrane.

Animals↗

PubMed1992

Quantitation of skeletal alkaline phosphatase isoenzyme activity in canine serum.

Pursuing the hypothesis that quantitation of skeletal alkaline phosphatase (ALP) activity in canine serum would provide an index of the rate of bone formation, we compared three methods for isoenzyme-specific identification of skeletal ALP activity in canine serum: heat inactivation, wheat germ agglutinin (WGA) precipitation, and concanavalin A (ConA) precipitation. ALP isoenzyme activities were extracted from canine bone, intestine, and liver, diluted into heat-inactivated canine serum (i.e., serum without ALP activity), and used as calibrators of ALP isoenzyme activities. Differential sensitivity to inhibition by 10 mM L-homoarginine was used to distinguish intestinal ALP activity from hepatic and skeletal ALP activities (i.e., 9, 80, and 72% inhibition, respectively). To allow resolution of skeletal ALP activity from hepatic ALP activity, we tested two established methods (heat inactivation and WGA precipitation) and a novel method, ConA precipitation. The organ-derived skeletal and hepatic ALP isoenzyme activities were used to compare these three methods with respect to linearity, isoenzyme separation, and precision. All three methods were linear, but the WGA and ConA methods afforded greater isoenzyme separation and precision. The relative extent of isoenzyme separation (i.e., the difference in percentage remaining skeletal and hepatic ALP isoenzyme activities) averaged 23, 40, and 47% remaining ALP activity for the heat, WGA, and ConA methods, respectively. However, when these methods were applied to the quantitation of skeletal ALP activity in sera from 10 young and 10 adult beagles, the WGA method was found to be unacceptable because most of the results fell outside the range of the WGA assay calibrators (i.e., greater than 100% skeletal ALP activity). The heat and ConA methods showed that the amount of skeletal ALP activity in the beagle sera decreased with age, both as ALP activity per liter and as percentage of total serum ALP activity (p less than 0.001 for each). Skeletal ALP activity levels determined by ConA were correlated with values determined by heat inactivation (r = 0.87, p less than 0.001) but not with WGA-determined levels (r = 0.26). Intestinal ALP activity was detected in only 1 of these 20 sera. We conclude that ConA precipitation can be used for quantitation of skeletal ALP activity in beagle serum.

Alkaline Phosphatase↗

PubMed1992

Automated microparticle enzyme immunoassay for neural thread protein in cerebrospinal fluid from Alzheimer's disease patients.

An automated microparticle enzyme immunoassay (MEIA) with the IMx analyzer for the detection of neural thread protein (NTP) in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients was developed. This assay uses monoclonal antibodies produced against the purified pancreatic form of the protein. The assay employs one monoclonal antibody covalently coupled to the microparticle to capture immunoreactive material in CSF or brain tissue. The second monoclonal antibody was conjugated to alkaline phosphatase and serves as detection antibody. The assay provides results in approximately 45 minutes with a sensitivity of 60 pg/ml (3 fmoles/ml). The titration curve of both normal and AD CSF resulted in a linear relationship with respect to the volume of CSF used. A similar relationship was observed when normal and AD brain tissue extracts were serially diluted. The molecular weight of NTP in CSF was approximately 20 kD as determined by gel filtration method under non-denaturing conditions. The recovery for pancreatic thread protein (PTP) spiked in either normal or AD CSF was 104% and 108%, respectively. Intra-, inter-, and total assay CVs (coefficient of variation) for controls were less than 2.9%, 3.3% and 3.0%, respectively. This assay will provide a useful tool in the study of the Alzheimer's disease and may help research in diagnosis and prognosis of Alzheimer's disease and related disorders.

Alzheimer Disease↗

PubMed1992

Immunochemical characterization of a monoclonal antibody specific for Alzheimer's disease associated protein.

In this study, the monoclonal antibody PHF-1 which recognizes epitopes unique to Alzheimer's disease associated proteins (ADAP) has been characterized. Crossed affinity immunoelectrophoresis was used to estimate the binding constant for the interaction of PHF-1 with ADAP and to estimate the fraction of PHF-1 reactive protein. The binding constant of PHF-1 was determined to be 1.3 x 10(-8) M. Furthermore, the effect of dephosphorylation on the electrophoretic pattern of the PHF-1 reactive protein and the ensuing changes in its immunoreactivity were demonstrated.

Alzheimer Disease↗

PubMed1992

Distribution of Alzheimer's disease-associated protein (ADAP) in 10 human brains.

ALZ50-based enzyme immunoassay was used to study distribution of Alzheimer's disease-associated protein (ADAP) in postmortem brain tissues of 5 Alzheimer's disease (AD) and 5 non-Alzheimer's disease (NAD) subjects. There are at least three AD-associated proteins, including A68. Levels are higher in brain regions with severe neuronal loss in AD: frontal, temporal, hippocampal cortex, and amygdala. No significant ADAP was found in the NAD samples (from 2 age-matched-1 clinically demented-and 3 younger subjects). ADAP levels in four regions of AD brains were not correlated to neuritic plaque count in corresponding regions of matching formaldehyde-fixed hemispheres.

Adult↗

PubMed1991

Tumor subpopulation interactions affecting melphalan sensitivity in palpable mouse mammary tumors.

Paired mixtures of melphalan-sensitive and relatively insensitive tumor cell subpopulation lines, originally derived from the same mammary tumor, were injected s.c. into syngeneic mice. When tumors were palpable, the mice were treated with melphalan at doses shown to be effective against the melphalan-sensitive subpopulations. Sensitivity was assessed by the loss of colony-forming ability of tumor cells harvested 1 to 14 days after treatment. When growing in tumors mixed with melphalan-sensitive line 4TO7 cells, line 66 (less sensitive) appeared much more sensitive than when it was grown alone. Line 66 tumors growing on the opposite sides of mice bearing line 4TO7 tumors were not more sensitive than when grown alone, indicating the lack of a systemic mechanism in the transfer of sensitivity from 4TO7 to 66. Furthermore, line 66 was not more sensitive when mixed with line 168TFAR (another melphalan-sensitive subpopulation) than when alone. The "transfer of sensitivity" from line 4TO7 to line 66 could be reproduced in collagen gel cultures but not in monolayer. Interestingly, line 4TO7, unlike line 168TFAR, is more sensitive to melphalan in collagen culture than in monolayer. This difference in sensitivity does not appear to be influenced by differences in cell density between the two culture systems. In collagen culture, the increased sensitivity of line 66 in the presence of line 4TO7 did not require cell contact and so appeared to act through diffusible factors(s). Collectively, these data suggest that the transfer of sensitivity is not dependent upon host factors or upon drug sensitivity per se but rather upon some mechanism requiring tumor cell-tumor cell interaction between specific subpopulation pairs. In additional studies, pH was ruled out as a factor in the transfer of sensitivity.

Animals↗

PubMed1991

The prognostic value of image analysis in ovarian cancer.

Histologic grading is very important for treatment decisions in ovarian cancer. All grading systems contain a significant subjective component, which could be reduced by including objective measurements into the diagnostic decision. Image analysis was used to determine nuclear area and ploidy distributions in 42 patients with epithelial ovarian cancer, and the results were related to tumor grade and clinical outcome. The mean nuclear area, mean optical density, number of hyperploid cells, and the standard deviation between measurements were significantly higher in Grade 2 and 3 tumors compared with Grade 1 tumors, in rapidly progressive tumors compared with less aggressive malignancies, and in recurrent tumors compared with primary lesions. The number of nuclei with very high DNA content was found to be of prognostic importance. Image analysis thus provides additional prognostic information in epithelial ovarian cancer.

DNA, Neoplasm↗

PubMed1991

Differential influence of organ site on three subpopulations of a single mouse mammary tumor at two distinct steps in metastasis.

Tumor subpopulations 66c14, 168FARN, and 4T07 are drug-resistant variants selected from sister subpopulations derived from a single mouse mammary tumor. These subpopulations are heterogeneous in their capacities to form experimental metastatic growth in the lungs and liver. Initial survival kinetics of arrested cells, determined by the clearance of 125IUdR-labelled cells, and subsequent growth rates, determined by sequential recovery of clonogenic tumor cells from occult metastases, both correlated with organ-colonizing potential as determined by necropsy. The growth rates of these 3 subpopulations were determined in vitro in monolayer and in situ in the subcutis, in the liver following intrasplenic injection, and in the lung following intravenous injection. Clonogenic potential of all 3 lines was similar in vitro (54-59%). Growth rates in vitro (population doubling times 16.5-21 hr) and in the subcutis (tumor volume doubling times 5.2-7.4 days) were similar for the 3 subpopulations, but differed significantly in the liver and lungs. For line 4T07, the most metastatic line to both lung and liver, population doubling times in vitro and in the lung and liver were similar, ranging from 17 to 26 hr. For lines 66c14 and 168FARN, the growth rates in lungs and livers were much slower than in vitro. Line 66c14, which is relatively more metastatic to the lungs, grew much faster in the lung (39 hours) than in the liver (91 hr), but line 168FARN, which is relatively more metastatic to the liver, grew at a faster rate in the liver (37 hr) than in the lung (63 hr). Thus, 3 tumor subpopulations (seeds) derived from a single tumor were differentially affected by host organ factors (soil) at 2 distinct stages in the metastatic process.

Animals↗

PubMed1991

Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line.

Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.

Animals↗

PubMed1991

Recent advances in the neurochemical pathology of Alzheimer's disease. Studies of neuropeptides, cholinergic function and Alzheimer's disease-associated protein.

Our findings from three postmortem tissue studies in Alzheimer's disease (AD) are presented. We investigated (1) alterations in somatostatin (SRIF) and corticotropin-releasing factor (CRF) in AD; (2) regulatory changes in presynaptic cholinergic function in AD; and (3) use of Alzheimer's disease-associated protein (ADAP) as a diagnostic test for AD in postmortem tissue. Taken together, these findings reveal marked reductions in SRIF and CRF concentrations in many cerebrocortical areas in AD, a marked up-regulation of cholinergic neuronal activity in surviving cholinergic neurons in AD, and excellent specificity and sensitivity for the use of the ADAP assay as a diagnostic test for AD in postmortem tissue.

Alzheimer Disease↗