Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma.
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DNA, Neoplasm↗
Biomedical subjects
A Bailey
Publications and source records attributed to A Bailey.
Length-based endotracheal tube and emergency equipment in pediatrics.
HYPOTHESIS: Pediatric endotracheal (ET) tubes can be accurately selected based on body length using a specialized emergency tape. POPULATION: Derivation set: Two hundred five children undergoing elective surgery. Validation set: Two hundred thirteen children undergoing elective surgery. Each child served as his or her own control. METHODS: Derivation phase: Two hundred twenty-one children undergoing ET intubation for elective surgery had their body length and leak pressures measured. The 205 children who had leak pressures between 10 and 40 cm H2O constituted the derivation set. The body length for a given ET tube size was derived from the interquartile range of patient lengths in this derivation set. Sizes for other resuscitative equipment items were chosen by a panel of experts using a modified Delphi technique. This information was placed by length on a color-coded tape. Validation phase: The tape was validated by using it to select ET tube size in another group of 203 children undergoing elective surgery. Criteria for acceptable fit in this group included leak pressure as above and the anesthesiologists' decision to accept the tube size or to retintubate. In the validation phase, length-based ET tube selections were compared with age-based rules: (age + 16)/4, and (age + 18)/4. RESULTS: The tape selected the appropriate ET tube size by leak pressure criterion in 77% of the cases and was within +/- 0.5 mm of the "correct" size 99% of the time. This was significantly better (P less than .005) than two widely used age-based rules, which gave the correct initial size in only 47% and 9% of these cases, and were within +/- 0.5 mm for 86% and 59%. The anesthesiologists chose to continue with the tape-sized tube rather than to reintubate in 89% of cases. CONCLUSION: A system for length-based selection of emergency equipment represents a significant adjunct to emergency physicians and paramedics who must deal with critically ill children. Length-based ET tube selection is clearly superior to age-based rules, which are difficult to remember and require accurate estimation of a patient's age.
Body Height↗
Seroprevalence of cytomegalovirus infection in a selected population in Jamaica.
The prevalence of antibodies to cytomegalovirus (CMV) was determined by the indirect enzyme-linked immunosorbent assay in a selected population of 2655 in Jamaica. The overall prevalence rate was 95%, increasing from 56.2% in children 1-4 years of age to 90% in the 15-19 years age group and by 25 years of age 97% of subjects had been exposed to CMV. The prevalence rate in children (58.4%) was significantly lower than that in blood donors (84%), sexually transmitted disease clinic attendants (95%) and antenatal women (97%) (p < 0.001). The prevalence rate in STD clinic attendants and pregnant women was also significantly higher than in blood donors (p < 0.05). The prevalence of CMV infection in the selected population, the clinical implications, routes of transmission and socioenvironmental factors are discussed.
Adolescent↗
Malignant histiocytosis X. A distinct clinicopathologic entity.
Histiocytosis X (HX) is characterized morphologically by a proliferation of Langerhans' cells (LC), and most often has an indolent, chronic course. To determine whether a distinct clinicopathologic entity of malignant histiocytosis X exists, the authors examined tissues from 31 patients with HX and divided them into four categories. Group A (19 patients) was characterized morphologically by benign-appearing LC and had an indolent course. The male:female (M:F) ratio was 10:9, and the mean age was 21 years (range, 2 months to 60 years). The immunophenotype of this group was S-100+, vimentin+, LN-2+, LN-3+, lysozyme-, LCA-, Leu-M1-. Group B (three patients) had benign-appearing LC, yet had an aggressive clinical course. All patients were male, with a mean age of 47 years (range, 3 years to 72 years). Organs involved included the liver, spleen, heart, thymus, lung, kidney, and pancreas. The immunophenotype was the same as for Group A. Group C (two patients) had atypical and malignant appearing LC, yet a relatively benign clinical course. The ages were four and 65 years, with one female and one male patient. In both patients, the cells were S-100+, vimentin+, LN-2+, LN-3+, and LCA-. Group D (seven patients) was characterized by atypical and malignant-appearing LC and an aggressive clinical course. The mean age was 25 years (range, congenital to 54 years) with one female and six male patients. Organs involved were the thymus, lungs, spleen, liver, kidney, brain, heart, pancreas, stomach, and muscle. Birbeck granules were found in two patients, and the one patient on which fresh tissue was available was CD1+. The typical immunophenotype was S-100+, vimentin+, LN-2+, LN-3+, Leu-M1-, lysozyme-. The results of our study indicate that (1) a distinct clinical entity of malignant HX, characterized morphologically by malignant-appearing LC and clinically by male predominance, atypical organ involvement, and an aggressive clinical course, does exist; and (2) the morphologic appearance of the LC is an imperfect predictor of the clinical severity of HX.
Adolescent↗
Characterization of a cDNA encoding a protein involved in formation of the skeleton during development of the sea urchin Lytechinus pictus.
In order to investigate the role of proteins in the formation of mineralized tissues during development, we have isolated a cDNA that encodes a protein that is a component of the organic matrix of the skeletal spicule of the sea urchin, Lytechinus pictus. The expression of the RNA encoding this protein is regulated over development and is localized to the descendents of the micromere lineage. Comparison of the sequence of this cDNA to homologous cDNAs from other species of urchin reveal that the protein is basic and contains three conserved structural motifs: a signal peptide, a proline-rich region, and an unusual region composed of a series of direct repeats. Studies on the protein encoded by this cDNA confirm the predicted reading frame deduced from the nucleotide sequence and show that the protein is secreted and not glycosylated. Comparison of the amino acid sequence to databases reveal that the repeat domain is similar to proteins that form a unique beta-spiral supersecondary structure.
Amino Acid Sequence↗
Monocytoid B-cell lymphoma in patients with Sjögren's syndrome: a clinicopathologic study of 13 patients.
A recent clinicopathologic study of a series of patients with monocytoid B-cell lymphoma (MBCL) indicated that there is a frequent association between MBCL and Sjögren's syndrome (SS) and raised the possibility of a relationship between these two disease entities. To further investigate the possible relationship of MBCL and SS, we studied pathologic and clinical characteristics of 13 patients with MBCL who had clinically documented SS. In all patients, the lymphoma had the characteristic morphologic features of MBCL, and immunologic and molecular hybridization studies confirmed the B-cell nature of the lymphoma. Twelve of the 13 patients were female, with a median age of 66 years at diagnosis. Eleven had localized disease and presented with either salivary gland or cervical lymph node enlargement; one patient presented with a breast mass, and another with generalized lymphadenopathy and hepatosplenomegaly. In five of 13 patients, the MBCL was associated with or progressed to large cell lymphoma. In two patients, there was bilateral involvement of the parotid gland; one had a synchronous high-grade lymphoma in both parotid glands. In two patients, bone marrow biopsies showed involvement by MBCL. Eleven patients are alive 2 to 55 months after the diagnosis of MBCL. One patient died with the disease 8 months after the initial diagnosis. Another patient died of an unrelated cause without evidence of disease 16 months after the diagnosis of MBCL. We conclude that there is a more than fortuitous association between MBCL and SS. This concept is consistent with previously reported observations of reactive monocytoid B cells in patients with benign lymphoepithelial lesions of salivary glands, which may result from selective homing of reactive monocytoid B lymphocytes to the benign lymphoepithelial lesions and their subsequent neoplastic transformation.
Adult↗
Effects of various fixatives and fixation conditions on DNA ploidy analysis. A need for strict internal DNA standards.
DNA ploidy and cell cycle analyses are being used with increasing frequency as additional, sometimes independent, biologic prognosticators of various malignancies. For obvious reasons, most of the large studies published are retrospective, using archival paraffin-embedded tissues likely to have been fixed and processed differently. To assess the effect of various fixation conditions on ploidy analyses, the authors performed a comprehensive study in which five contiguous aliquots from 26 tissue samples were fixed in formalin for 8. 24, and 48 hours; B5; and the ethanol-based fixative Omnifix (Omni, Xenetics Biomed Inc., Irvine, CA), respectively. The samples were prepared and stained with the use of Hedley's method; the DNA analyses were done with a Coulter EPICS V flow cytometer (Coulter Electronics, Hialeah, FL); and the resulting histograms were interpreted with Multicycle software (Phoenix Flow Systems, San Diego, CA). Mean channels and coefficients of variation (CVs) of the G0/G1 peaks were compared. Increasing fixation times in formalin produced slight shifting to the left on the G0/G1 peaks with differences up to 13 channels. Omni caused similar but more conspicuous changes, with maximal shifting of 51 channels. B5 created the opposite effect, with right-shifted G0/G1 peaks up to 22 channels. The CVs deteriorated progressively with increasing fixation times in formalin. B5 and Omni fixatives conferred the worse histograms, with 6 and 15 cases, respectively, displaying CVs greater than 8. Such significant differences preclude the use of any other internal standard but adjacent normal tissue that was processed exactly the same as the tumor. The validity of DNA results obtained otherwise should be considered questionable. These findings may explain some of the previously published controversial reports and emphasize the need to use an internal standard and more stringent criteria to define aneuploidy in paraffin-embedded tissue.
Cell Cycle↗
Hospital closure: maintaining staff morale.
Closing a large psychiatric hospital is a complex exercise, and one of the main tasks for management is to maintain staff numbers and staff morale during the run-down period, and to help staff find new and rewarding roles in the community based service. Alistair Bailey and Martin Barkley explain how this was tackled at Netherne Hospital.
England↗
Seroprevalence of toxoplasma gondii, rubella virus, cytomegalovirus herpes simplex virus (TORCH) and syphilis in Jamaican pregnant women.
Seroprevalence of toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus infections (TORCH) and syphilis were determined in order to assess the immune/susceptibility status in Jamaican pregnant women in 1986. The positive rates were 57% (T. gondii), 69% (rubella), 97% (CMV), 91% (HSV), and 4.9% (syphilis), respectively. The rate of reactivity for syphilis ranged from 2.1% in Kingston and St. Andrew to 7.3% in rural parishes. The seropositivity rate for rubella was over 50% in all parishes, the highest being 85% in St. Thomas. The seroprevalence of T. gondii was lowest in Trelawny (37.5%). There were no significant differences in seropositivity of CMV and HSV infections between women from various parishes. The importance of seroprevalence of the TORCH group of agents and syphilis on perinatal morbidity and mortality in Jamaican women is discussed, and appropriate recommendations for prevention and control of congenital infections in Jamaica are suggested.
Adolescent↗
Immunohistochemical assay of neu/c-erbB-2 oncogene product in paraffin-embedded tissues in early breast cancer: retrospective follow-up study of 245 stage I and II cases.
The expression of neu oncoprotein was assayed by immunohistochemistry (IHC) on 245 paraffin-embedded, Stage I and II breast cancers from patients treated at the City of Hope between the years 1980 and 1987. Only cases showing membrane staining were scored as positive. Fifty-four (22%) of the tumors stained positively for neu. Probability of disease-free survival (DFS) and overall survival (OS) was compared based on neu positivity and other prognostic factors. Overall, DFS and OS did not differ significantly among neu-positive and neu-negative cases. However, when only cases with favorable (Stages I and II) nuclear grade were analyzed, OS and DFS were significantly lower in neu-positive cases, with a 9-fold increase in risk of death and a 3-fold increase in risk of relapse. Our findings suggest that immunohistologic study of neu oncoprotein may help to define patients at greater risk among low-stage/low-nuclear-grade patients with breast cancer, a group hitherto recognized as having a good prognosis.
Adult↗
Induced proto-oncogene expression increases susceptibility to radiation-induced carcinogenesis.
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3T3 Cells↗
Quantification of estrogen receptors on paraffin-embedded tumors by image analysis.
Emphasis on early detection of breast carcinomas has increased the number of instances in which an insufficient amount of tissue is available for biochemical estrogen receptor (ER) assay. Image analysis, used together with immunohistochemistry, introduces the possibility of quantifying molecules, such as ER, in routinely processed tissues. To explore that possibility, sections from 40 formalin-fixed, paraffin-embedded breast carcinomas with biochemically determined ER values were reacted with H222 anti-ER antibody (ER-ICA) and quantified on a CAS 200 image analysis system. A minimum of ten fields comprising at least 15,000 microns 2 of nuclear area were analyzed in each case. If the antigen distribution were not homogeneous, proportional sampling of the different tumor areas was carried out. Of the 31 ER-positive (10 to 344 fmol/mg) tumors, 27 (87%) were immunoreactive by the ER-ICA assay (greater than 5% positive nuclear area), which represents an improvement over simple microscopic evaluation (68%). Bivariate analyses showed statistically significant, albeit only modest, correlation between ER values and the percentages of positive area (r = 0.556) and positive stain (r = 0.518). The following obstacles were found to interfere with a proper correlation: (a) antigen loss during fixation and processing; (b) intratumoral antigenic heterogeneity; and directly associated with it, (c) interobserver variability. Uniform tissue handling or, alternatively, the use of internal controls to compensate for fixation-induced differences, together with thorough assessment of the tissue, should reduce these obstacles and facilitate accurate and reproducible quantification.
Antibodies, Monoclonal↗
Laparoscopic laser cholecystectomy and choledocholithiasis.
The management of common bile duct stones during laparoscopic laser cholecystectomy (LLC) is uncertain. Open common bile duct exploration is the least desirable option since it defeats the purpose of LLC. Endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy has become the procedure of choice since it has a high rate of success and results in minimal morbidity. Intraoperative techniques using balloon catheters and the flexible choledochoscope via the cystic duct may obviate the need for ERCP in selected cases.
Cholangiopancreatography, Endoscopic Retrograde↗
Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis.
The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right.
Autoantibodies↗
Genetic factors in child psychiatric disorders--II. Empirical findings.
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Adolescent↗
Erythrocyte autoantibodies, subclasses of IgG and autoimmune haemolysis.
The subclass pattern of red cell bound IgG autoantibody was studied in 304 patients on 426 occasions. Subclass interrelationships with time, other cell bound immunoglobulins (IgM, IgA), amount of bound IgG and serum haptoglobin levels were investigated using population proportions; because of the multiple statistical tests, P less than 0.01 was required for significance. IgG1 was most common, being found in 98% of cases and as the sole subclass in 64%; multiple subclasses occurred in 34.5%. The IgG subclass pattern possibly changed with time (P less than 0.02, greater than 0.01), populations being compared at 6 and 12 months. There was a highly significant and important correlation between multiple IgG subclasses and multiple immunoglobulin coating; in our further studies, this necessitated the use of samples where only cell bound IgG was increased. Multiple IgG subclasses strongly correlated with larger amounts of cell bound IgG, groups with greater than 2 and less than 1 OD units by the enzyme-linked direct antiglobulin test being compared (approximately greater than 800 and less than 400 molecules IgG per red cell respectively). Multiple subclasses (P less than 0.05, greater than 0.01), but not IgG3, were possibly associated with low haptoglobin levels; significance was reached, however, if the multiple immunoglobulin effect was ignored. IgG subclass interrelationships are clearly complex and require strictly defined populations for their study.
Adolescent↗
Stimulation of renal and hepatic c-myc and c-Ha-ras expression by unilateral nephrectomy.
Unilateral nephrectomy induces compensatory hypertrophy of the contralateral kidney in rats, resulting in a 25% weight increase in 14 days. We have demonstrated that expression of the c-myc and c-Ha-ras protooncogenes is increased more than ten-fold in the contralateral kidney within 4 to 8 hr following unilateral nephrectomy in rats. The increased expression of these genes is analogous to the increased expression of c-myc and c-Ha-ras that occurs early in liver regeneration, preceding the first increase in DNA synthesis by at least 20 hr. In order to define the tissue specificity of the signals for compensatory renal hypertrophy, we also determined the early protooncogene response and the proliferative response in the liver of rats following unilateral nephrectomy. The expression of c-myc and c-Ha-ras was also increased (five- to ten-fold) in the livers of these animals. DNA synthesis was stimulated in the contralateral kidney at 26-30 hr following nephrectomy as measured by 3H thymidine incorporation, indicating a hyperplastic response to unilateral nephrectomy. However, there was no increase in DNA synthesis in the liver despite the dramatic increase in c-myc and c-Ha-ras expression. Our data suggest that the early increase in protooncogene expression in response to unilateral nephrectomy is stimulated by circulating signals that are not tissue-specific. Increased protooncogene expression in both kidney and liver following unilateral nephrectomy is an early response to the regenerative stimulus, but later signals must provide the tissue specificity necessary for regeneration and cellular proliferation.
Animals↗
Unique sequence organization and erythroid cell-specific nuclear factor-binding of mammalian theta 1 globin promoters.
The theta 1 globin gene is an alpha globin-like gene, and started to diverge from the other members of the alpha globin family 260 million years ago. DNA sequencing and transcriptional analysis indicated that it is functional in erythroid cells of the higher primates, but not in prosimians and rabbit. The theta 1 promoter region of higher primates including man consists of GC-rich sequences characteristic of housekeeping gene promoters, and CCAAT and TATA boxes located further upstream. It is shown here that the housekeeping gene promoter-like region of human theta 1 contains two tandemly arranged, GC-rich motifs (GC-I and GC-II). Of these, GC-II interacts with nuclear factor(s) present in the globin-expressing, erythroleukemia cell line K562, before and after hemin induction. GC-I, however, interacts with nuclear factor(s) only present in hemin-induced K562 cells. These factors are different from previously reported erythroid cell-specific factors, and are not detectable in non-erythroid Hela cells. Furthermore, the sequence of the motif GC-I and its location relative to ATG codon have been conserved among all known mammalian theta 1 globin genes. Finally, and most interestingly, the CCAAT box of theta 1 is contained within a 38 bp internal segment of Alu repeat sequence. Immediately upstream from this CCAAT box-containing Alu repeat segment is a 241 bp Alu repeat pointing in the opposite direction. The conservation of this novel arrangement among the higher primates suggests that an inserted Alu family repeat and its flanking genomic sequence have co-evolved, for at least 30 million years, to provide the canonical CCAAT and TATA promoter elements of the theta 1 globin genes in higher primates.
Animals↗