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Biomedical subjects

S R Taylor

Publications and source records attributed to S R Taylor.

At least 37 records · Page 2Linked to original sources

Some small prostate cancers are nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid ploidy status and pathological features.

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.

Cell Nucleus↗

Carcinoma of prostate metastatic to parotid gland.

A rare case of prostate cancer with metastasis to the parotid salivary gland is reported. The prostatic origin of the mass was proven by incisional biopsy and immunohistochemical staining for prostate-specific antigen. Additional studies of the tumor included ultrastructural and quantitative deoxyribonucleic acid (DNA) analysis.

Adenocarcinoma↗

DNA content and other prognostic features in childhood medulloblastoma. Proposal of a scoring system.

The authors reviewed clinical features, surgical extent of resection, histologic parameters, and DNA content in 55 children with medulloblastomas and found that complete or near total resection, absence of tumor dissemination, tumor DNA aneuploidy, and low proliferative index correlated with a favorable clinical outcome. A scoring system was developed based upon these features to identify patients who, in the future, may benefit from more aggressive or novel therapeutic regimens. Patient age and sex and adjuvant chemotherapy did not significantly correlate with long-term survival. The data also suggest that tumors that have been designated as cerebellar neuroblastomas may be a distinct group of posterior fossa tumors, which may have a better prognosis.

Adolescent↗

Volume changes during contraction of isolated frog muscle fibers.

A microscope objective and electronic imaging system were used to determine how isolated frog skeletal muscle fibers adjust their volume during an isometric tetanus. Cross-sectional area and volume of the middle third of a fiber increased rapidly with the development of active tension, which indicates that contraction produced components of force perpendicular to the long axis. The extreme ends are known to shorten whether or not the middle of a fiber is isometric or stretched. Shortening of the ends may shift water towards the middle, which could account for the volume changes we observed. The cytoskeletal matrices of muscle evidently adjust rapidly during contraction to maintain a dynamic equilibrium between the axial and radial forces that stabilize the whole cell. The Z disks have been shown to expand during active, but not passive, tension development. Z disks might be the elastic elements of the muscle cytoskeleton primarily involved in rapid balancing of the radial components of active force.

Animals↗

DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report.

The malignant potential of an individual focus of prostate cancer is difficult to determine. The established pathological features associated with malignant behavior include tumor volume, grade, and invasiveness (local extension or metastasis). We used nuclear image analysis to determine the DNA ploidy value of each cancer in a series of 30 radical prostatectomy specimens from patients with early stage prostate cancer in order to further explore the malignant potential of each separate focus of cancer. The volume, grade, invasiveness (extracapsular extension or seminal vesicle invasion), and zone of origin of each of the 63 separate cancers were determined. The DNA ploidy histogram of 200 cancer cells was compared with 50 normal epithelial nuclei on the same Feulgen-stained tissue sections. Sixty % of the cancers were diploid, and 40% were nondiploid. Ploidy correlated with volume and grade. All cancers less than 0.02 cm3 were diploid; 26% of foci 0.02 to 2.0 cm3 and 82% of foci greater than 2.0 cm3 were nondiploid. There were 16 cancers of transition zone origin ranging in size from 0.02 to 12.1 cm3 and only one (7.3 cm3) was nondiploid. There were 47 cancers of peripheral zone origin (range, 0.01 to 18.98) and 24 (51%) were nondiploid. Eight of the 24 nondiploid cancers were small (less than 1.0 cm3), and two were only 0.03 cm3. We conclude that some very small prostate cancers are nondiploid and that progression of prostate cancer is not a function of volume alone, whereby tumors only acquire full malignant potential at large volumes. Cancers of peripheral zone origin acquire a nondiploid cell population at a smaller volume than do cancers of transition zone origin, further supporting a fundamental difference between cancers arising in these zones.

Cell Differentiation↗

Isolation and characterization of parvalbumins from skeletal muscles of a tropical amphibian, Leptodactylus insularis.

Parvalbumins were isolated from skeletal muscles of a tropical amphibian, Leptodactylus insularis, and three new isotypes were identified. The total concentration of parvalbumins in L. insularis was the same as the total amounts found in an amphibian from the temperate or variable zone (Rana temporaria). Muscles of the thigh and foreleg had the maximum parvalbumin concentration (0.35 mmol.kg wet weight-1). Samples from pectoralis and rectus abdominis muscles had significantly less (0.29 mmol.kg-1). Three previously unknown parvalbumin isotypes (IV, IIIa, and IIIb) were isolated from the tropical amphibian. They were different from the isotypes (IVa and IVb) predominant in R. temporaria skeletal muscle. Parvalbumins are thought to have a role in the short-term removal of myoplasmic Ca2+ during muscle relaxation. Hence, the unique isotypes in L. insularis may reflect optimal molecular adaptations retained during the animal's evolution in a constantly warm environment.

Amphibians↗

Quantitative DNA analysis of small renal cortical neoplasms.

DNA aneuploidy is common in large renal cortical neoplasms (RCNs), but the incidence in small RCNs is not known. This study was undertaken to investigate whether the traditional 3.0-cm size distinction between small (benign) and large (malignant) tumors might have an objective correlate in the form of abnormal DNA content. Quantitative DNA analysis was performed retrospectively, by image analysis, on 59 RCNs measuring 5.0 cm or less from 30 nephrectomy specimens with solitary tumors and 17 with multiple tumors. DNA indices and the proportion of cells with DNA content greater than that of the G0/G1 population were evaluated with respect to tumor size, stage, and histologic parameters. There was a relationship between the presence of detectable nondiploid stem lines (NDSLs) and tumor size, stage, nuclear grade, and proportion of non-G0/G1 cells, but not histologic pattern. The relationship of NDSLs to tumor size was more apparent in the solitary tumor group, while the relationship of a high proportion of non-G0/G1 cells to tumor size was stronger in the multiple tumor group. Our results show that the incidence of NDSLs increases with tumor size and nuclear grade, and suggest that as RCNs enlarge, the emergence of NDSLs heralds potential biologic aggressiveness. Further, solitary tumors and multiple synchronous tumors may be biologically different in terms of etiologic factors and growth potential.

Adenoma↗

Nonuniform volume changes during muscle contraction.

We measured dynamic changes in volume during contraction of live, intact frog skeletal muscle fibers through a high-speed, intensified, digital-imaging microscope. Optical cross-sections along the axis of resting cells were scanned and compared with sections during the plateau of isometric tetanic contractions. Contraction caused an increase in volume of the central third of a cell when axial force was maximum and constant and the central segment was stationary or lengthened slightly. But changes were unequal along a cell and not predicted by a cell's resting area or shape (circularity). Rapid local adjustments in the cytoskeletal evidently keep forces in equilibrium during contraction of living skeletal muscle. These results also show that optical signals may be distorted by nonuniform volume changes during contraction.

Animals↗

Vagal paragangliomas: a clinical, pathological, and DNA assessment.

Ten vagal paragangliomas were studied by image analysis and the results correlated with clinicopathologic features to determine if the DNA ploidy pattern could be used to separate benign from malignant paragangliomas. The tumours occurred in 8 women and 2 men ranging in age from 23 to 75 years (average 54 years). Follow-up was available in all 10 patients and ranged from 3 months to 27 years (average 7.8 years). Of the 10 tumours examined for DNA, 5 were diploid, 4 diploid-tetraploid, and 1 aneuploid. Two patients experienced local recurrences. One of these had a diploid tumour that recurred 22 years after excision and the other had an aneuploid tumour which recurred 4 years 4 months later and was associated with cervical lymph node metastasis. Two patients had malignant tumours with histologically confirmed metastases to noncontiguous cervical lymph nodes. One of the malignant tumours was diploid and the other aneuploid. This study concludes that DNA abnormalities are common in vagal paragangliomas and that tumour ploidy can not be used to assess malignant potential.

Adult↗

Effects of putative modulators of relaxation microinjected into intact amphibian smooth muscle cells.

1. Single smooth muscle cells were isolated intact from the stomach of the toad Bufo marinus. The relaxation of cells following cessation of electrical stimulation was compared with those relaxed by pressure microinjection of either metal ion chelators or cyclic nucleotides. 2. Injection of either a Ca2+ chelator or 3',5'-cyclic AMP slowed or halted shortening and promoted re-extension of a cell or collapse of membrane evaginations (blebs) in a manner similar to that following cessation of electrical stimulation. Collapse of blebs occurred first and was then followed smoothly by the next stage with cells re-extending at maximum rates in one of three ranges at 22 degrees C. These rates, in order of increasing speed, were 0.005, 0.009 and 0.03 cell lengths s-1 after electrical stimulation, 3',5'-cyclic AMP and EDTA injection, respectively. On the other hand, shortening began at a maximum rate of about 0.1 cell lengths s-1 unless a Ca2+ chelator or 3',5'-cyclic AMP was injected about 30 s or less before electrical stimulation. Injection of these agents reduced the speed of shortening by about half. 3. Injection of a liquid per se (e.g. 140 mM-KCl) neither altered action potentials nor duplicated the changes produced by the aforementioned relaxing agents. Large, sustained injections of substances that were not relaxing agents (e.g. dilute KCl) ruptured the membrane without producing any bleb collapse or re-extension of a contracted cell. Blebs not only collapsed rapidly when a relaxing agent was injected but bleb collapse was a much more sensitive indication of relaxation than cell re-extension; small injections of relaxing agents could clearly collapse blebs with no associated measurable change in cell length. This supports the idea previously inferred from fixed or permeabilized cells, that filaments in smooth muscle are organized to produce force over short distances at points along the cell membrane, in addition to shortening along the long axis. 4. Physiological relaxation of smooth muscle can evidently be mimicked by 3',5'-cyclic AMP elevation. Restoring forces may develop during shortening of isolated smooth muscle cells in elements of their cytoskeleton, surface membrane, or contractile filaments. However, these putative forces may not be able to produce physiological re-extension in the absence of a rise in cyclic AMP and/or a fall in [Ca2+].

Animals↗

Fatal pulmonary aspergillosis presenting as acute eosinophilic pneumonia in a previously healthy child.

A previously healthy boy presented with cough and diffuse pulmonary interstitial infiltrates. Acute eosinophilic pneumonia was diagnosed by bronchoalveolar lavage in the absence of a demonstrable infectious etiologic agent. Corticosteroid therapy resulted in immediate improvement but was followed by respiratory distress and death from invasive aspergillosis and Pseudomonas cepacia sepsis.

Acute Disease↗

DNA analysis of multiple synchronous renal cell carcinomas.

The authors used retrospective quantitative DNA analysis to study interrelationships between multiple synchronous renal cell carcinomas in seven patients. DNA content was determined by image analysis on Feulgen-stained nuclear smears prepared from multiple paraffin blocks from each tumor. Tumors were unilateral in four cases and bilateral in three. Ten tumors had homogeneous, and four heterogeneous DNA stemlines. Intertumoral heterogeneity in four cases suggested multifocal origin. Identical DNA aneuploid indices in bilateral tumors in one case suggested metastasis from a solitary origin. Abnormal DNA content and heterogeneous populations began to appear in the size range 2.0 to 5.0 cm. All tumors over 5.0 cm contained nondiploid populations. Although the interrelationships between these multiple synchronous neoplasms are not entirely clear, the DNA analysis suggests that the occurrence of nondiploid stemlines and heterogeneous DNA content may parallel both tumor growth and more aggressive behavior.

Adult↗

A comparative analysis of nuclear DNA content and N-myc gene amplification in neuroblastoma.

Nuclear DNA content and N-myc amplification have been found to have prognostic significance in neuroblastoma. To investigate the interrelationships between these two parameters, tumor samples from 18 patients with neuroblastoma were analyzed for both total DNA and N-myc gene content. Quantitative DNA analysis was performed by image analysis. Quantitative Southern blot hybridization was used to determine N-myc gene copy number and to distinguish between low level gene amplification or excess gene copies secondary to aneuploidy. Six of the 18 patients have died. Five of the six had nonaneuploid tumors, but only two of the six exhibited major N-myc amplification. Low-level amplification was detected in one Stage II patient. The authors' results suggest that neuroblastomas with N-myc amplification are a subset of nonaneuploid tumors.

Blotting, Southern↗

Carotid body paragangliomas. A clinicopathologic and DNA analysis of 13 tumors.

The clinical and pathological features of 13 carotid body paragangliomas from 12 patients were examined and correlated with the DNA ploidy pattern as determined by image analysis. These tumors occurred in 7 women and 5 men aged 19 to 62 years (average, 42 years). All presented with a slowly enlarging, usually asymptomatic mass of 2 weeks' to 25 years' duration. Two patients were related and had a family history of paragangliomas. The tumors ranged from 2 to 6 cm. All contained scattered chief cells with pleomorphic nuclei, two exhibited mitoses, and three showed perineural and three vascular invasion. Follow-up was available in all 12 patients and ranged from 15 months to 28 years (average, 7.3 years). None of the tumors recurred locally, but one did metastasize to a single cervical lymph node that was apparent at the time of diagnosis. Of 13 carotid body paragangliomas examined for DNA, 4 were diploid, 3 diploid-tetraploid, 3 tetraploid, 2 aneuploid, and 1 polyploid. The only malignant tumor was polyploid. From these observations, we conclude that abnormalities in DNA content of carotid body paragangliomas are common and that tumor ploidy cannot be used to assess malignant potential. We also found no apparent relationship among nuclear pleomorphism, mitotic activity, perineural invasion, or vascular invasion and clinical behavior. Perineural and vascular invasion, however, were observed only in tumors with abnormal DNA histograms.

Adult↗

Severe chemotherapy-related hepatic toxicity associated with MZ protease inhibitor phenotype.

We describe a 10 1/2-month-old boy in whom fulminant hepatic failure following chemotherapy for Wilms' tumor developed. He then received an orthotopic liver transplant. An unexpected finding was the accumulation of alpha 1-antitrypsin (AAT) in periportal hepatocytes. A pretransplant serum sample showed a Pi MZ phenotype. The rarity of hepatic failure following treatment for Wilms' tumor raises the possibility of an increased susceptibility to toxic injury in the presence of AAT accumulation. Determination of the frequency of protease inhibitor MZ phenotype in patients who have chemotherapy-related hepatotoxicity could be used to initiate a prospective study aimed at identifying an at-risk population for chemoradiotherapy-related hepatoxicity.

Alleles↗

Typical and atypical carcinoid tumors of lung: a clinicopathologic and DNA analysis of 20 tumors.

Twelve typical carcinoid tumors (TCT) and eight atypical (malignant) carcinoid tumors (ACT) of the lung were studied for quantitative DNA content by image analysis in order to identify prognostic features. No correlation of any histologic variables of the TCTs and ACTs with abnormal DNA content were noted. Furthermore, it was concluded that although abnormalities of DNA content, particularly aneuploidy, are common in ACTs, DNA ploidy cannot be used independently to assess malignant potential.

Adult↗

Three infants with acute megakaryoblastic leukemia simulating metastatic tumor.

The diagnosis of acute megakaryoblastic leukemia (AMKL) (M7, French-American-British [FAB] classification) has rarely been made in children due, in part, to its pleomorphic morphology and ability to mimic other malignancies common in the pediatric age group. Three infants are described who had thrombocytopenia and the classical criteria of metastatic solid tumor in the bone marrow: patchy infiltration by cohesive clusters of cells with high nuclear cytoplasmic ratio and myelofibrosis in the bone marrow biopsy infiltrated area. This finding prompted clinical evaluation for solid tumor. The megakaryocytic lineage was ascertained by immunocytochemical studies and/or electron microscopic examinations of the bone marrow aspirates. The blasts in all three patients showed cytogenetic abnormalities that also were demonstrated by quantitative DNA analysis. None of the infants had Down's syndrome. Two of the patients are alive; one is off of therapy and the other is in remission. The third patient was transferred to another institution and lost to follow-up. Two children had wheezing that disappeared in remission. It is proposed that the clinical symptoms may be due to a substance produced, stored, or released by the leukemic cells.

Adolescent↗