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Biomedical subjects

S Cole

Publications and source records attributed to S Cole.

At least 127 records · Page 7Linked to original sources

Immunohistochemical evaluation of pleural mesothelioma and pulmonary adenocarcinoma. A bi-institutional study of 47 cases.

Pleural mesotheliomas and peripheral pulmonary adenocarcinomas were evaluated by immunohistochemistry at two institutions (Yale University School of Medicine and the City of Hope National Medical Center). Twenty-three mesotheliomas, 11 with ultrastructural verification, and 24 pulmonary adenocarcinomas were studied. Antikeratin, anticarcinoembryonic antigen, anti-human milk fat globule related antigen, MC-1, B72.3, and Leu M-1 antibodies were employed. The immunohistochemistry of each case prepared at one institution was reviewed at the other. As groups, the two tumor types were distinguishable using this antibody panel. Essentially, mesotheliomas were keratin positive only. The adenocarcinomas were positive for CEA, MFG, B72.3, and Leu M-1. However, there were some ambiguities presented by the immunohistochemistry. The higher molecular weight keratins were found in most but not all mesotheliomas and in only a few adenocarcinomas. Lower molecular weight keratins were positive not only in all the mesotheliomas, but also in nearly all the adenocarcinomas, but also in a tumor determined by electron microscopy to be mesothelioma. Preabsorption of CEA decreased the sensitivity for adenocarcinoma, but did not change the positivity of the putative mesothelioma. B72.3 and Leu M-1 were specific for adenocarcinoma, but were found in only half of them. The MFG was apparently specific for adenocarcinoma, but the findings were difficult to interpret. At the level of individual cases, greater sensitivity of separation can be achieved by combining the results of two or more antibodies, but the lack of a detectable specific antigen in mesothelioma continues to make some cases difficult to evaluate by immunohistochemistry alone.

Adenocarcinoma↗

Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters.

The interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). The basis of this was investigated using the 139A strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. Cloned scrapie was passaged through hamsters (twice) or rats (thrice) and then reisolated in mice. Large species barrier effects were encountered on mouse-to-hamster and hamster-to-mouse passage resulting in the isolation of a mutant strain, 139-H/M, with properties very different from 139A. In contrast, the strain reisolated from rats was indistinguishable from 139A. However, a large species barrier was encountered at the mouse-to-rat passage but not at the rat-to-mouse passage. It is suggested that the transmission of scrapie between species may be associated with no change in properties or a permanent change in the scrapie genome due to the selection of mutants. A third possibility, the donor species effect, is a temporary change occurring only at first passage in the new host species which is largely or entirely caused by the introduction of material from the previous host. We speculate that the donor species effect could be explained if some host protein forms a functional part of the infectious agent.

Animals↗

Quantitative studies of the fate of epidermal Langerhans cells after X-irradiation of guinea-pig and mouse footpad skin.

Langerhans cell numbers, morphology and distribution were observed in cross sections of footpad epidermis at intervals from 1 to 28 days after exposure of the hind feet of CBA/H mice or albino guinea-pigs to a single absorbed dose of 20 Gy (2000 rad) of X-rays. In mice, the number of Langerhans cells reactive with anti-macrophage F4/80 monoclonal antibody steadily declined by approximately 85% within 10 days after irradiation, consistent with previous studies, in which Langerhans cells were identified in epidermal sheets by ATPase activity or presence of Birbeck granules. Remaining Langerhans cells were exceptionally dendritic. Very few Birbeck granule-containing cells were found in murine popliteal lymph nodes before or after irradiation but damaged cells were present in superficial strata of irradiated epidermis. The morphology and number of epidermal F4/80-positive cells approached normal by 15 days after irradiation. In guinea-pigs, gradual suprabasal movement and loss of rounded, ATPase-positive Langerhans cells from the epidermis were detectable from 5 to 20 days after irradiation but the magnitude of the cell loss and redistribution was partially obscured by the simultaneous appearance of clusters of replacement Langerhans cells in the basal layer and by keratinocyte hyperplasia.

Adenosine Triphosphatases↗

Mucin production in cervical intraepithelial neoplasia and in stage 1b carcinoma of cervix with pelvic lymph node metastases.

Sections from cervical intraepithelial neoplasia (CIN 3) and stage 1b carcinoma of the cervix were stained with periodic acid-Schiff (PAS) and alcian blue to identify the presence of intracellular mucin. One out of seven specimens of CIN 3 demonstrated intracellular mucin. In a series of 33 patients with stage 1b carcinoma of the cervix with pelvic lymph node metastases, PAS demonstrated intracellular mucin staining patterns that were similar in both tumour and lymph node in most patients. In the subgroup of 23 patients classified as having squamous carcinoma, 8 (35%) demonstrated intracellular mucin to some degree and only 2 (25%) of those 8 were alive after 3 years compared with 13 of the other 15 (87%) who did not show any mucin staining (P less than 0.01).

Adenocarcinoma↗

A modified adenosine polyphosphatase histochemical method to demonstrate Langerhans cells in fragile epidermis.

Adenosine polyphosphatase enzymes provide useful markers for epidermal Langerhans cells. Established adenosine polyphosphatase histochemical methods were refined and applied to demonstrate Langerhans cells in thin sheets of murine dorsal epidermis. The skin was supported during staining by attaching the keratinized surface to polyallyl diglycol carbonate "plastic" slides with cyanoacrylate adhesive and flattening it with pressure from a glass slide on the dermal surface. Optimal specific staining of dendritic Langerhans cells occurred after fixation of ethylenediaminetetraacetic acid-separated epidermal sheets in cacodylate buffered formaldehyde for 20 min and incubation, in the presence of magnesium and lead ions, with 9.36 X 10(-4) M adenosine diphosphate (ADP) for 45 min. Better definition of the cells was obtained with ADP as a substrate than with any concentration of adenosine triphosphate.

Adenosine Triphosphatases↗

Ranitidine potentiates ileum contractions caused by GABA and electrical stimulation.

GABA-evoked contractions of the guinea pig ileum were significantly potentiated by the histamine H2-receptor antagonist ranitidine in concentrations above 10 microM. To help define the mechanism of this interaction, the present study compared the effects of ranitidine on contractile responses of the guinea pig ileum to GABA, acetylcholine (A Ch) and electrical stimulation of intrinsic cholinergic neurons. Ranitidine, at concentrations that potentiated responses to GABA, also potentiated contractions induced by transmural electrical stimulation. The ability of ranitidine to amplify these latter responses was antagonized by atropine. Contractile responses to exogenous A Ch, however, were unaffected by ranitidine at any concentration. These results suggest that prejunctional, rather than postjunctional mechanisms, are of primary importance in the interaction between ranitidine and GABA.

Animals↗

Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of hemoglobin--implications for therapy.

The drug BW12C, which increases the oxygen affinity of hemoglobin, reduces oxygen availability to tissues. This results in protection against radiation damage to the hemopoietic system and epidermal Langerhans cells in CBA mice. The drug also protects against beta-irradiation damage in pig epidermis. BW12C increases the hypoxic cell fraction in tumors and histological examination of an experimental T cell lymphoma shows that the induced hypoxia leads to tumor necrosis.

Aldehydes↗

Long-term effects of local ionizing radiation treatment on Langerhans cells in mouse footpad epidermis.

Langerhans cells (LC) were studied with ADPase histochemistry in sheets of hind footpad epidermis from groups of CBA/H mice. Single, local 20-Gy doses of 250-kV x-rays were administered to the right hind feet of the mice when they were 3-4 months old, and LC were counted at intervals ranging from 2 to 24 months later. In unirradiated mice, aged 5-19 months, the mean density of LC in footpad was 1521-1617 cells/mm2. It dropped to 1137 +/- 86 cells/mm2 (mean +/- SE) in untreated 28-month-old mice. At times from 2-15 months after irradiation, normal mean densities of LC were present in footpad epidermis. On average, LC numbers were subsequently reduced to 1078 +/- 65/mm2 by 19 months after irradiation (71% of the cells in age-matched controls) and to 789 +/- 53/mm2 by 24 months (59% of the cells in age-matched controls). Loss of cells was focal. Chronic radiation-induced fibrosis and damage to circulatory function in skin may have contributed to impaired replacement of LC from bone marrow precursors. The possibility that late radiation-related depletion of the LC population permits development of skin tumors as a delayed consequence of exposure to ionizing radiation is discussed.

Age Factors↗

Comparisons of data from regional perinatal mortality surveys.

The standard format in which NHS regions are invited to submit data from their perinatal mortality surveys for comparative analysis in the British Journal of Obstetrics and Gynaecology is described. Some examples of the way these data can and will be used to compare regional differences in mortality patterns are given and possible future developments are discussed. Although the term perinatal mortality is used in the title, it is hoped that surveys will cover stillbirths and neonatal deaths and also, where possible, late fetal deaths of less than 28 weeks gestation.

Birth Weight↗

Linkage of DNA markers to cystic fibrosis in 26 families.

Two DNA markers, the met oncogene and the anonymous probe, pJ3.11, previously reported to be tightly linked to cystic fibrosis (CF), were used for linkage analysis in 26 families with two or more individuals affected with CF. A new high frequency polymorphism was identified using BanI and the pmetD probe. The results of linkage analysis were as follows: between met and CF, lod score of 18.2 at theta of .009; between pJ3.11 and CF, lod score of 12.1 at theta of 0; and between met and pJ3.11, lod score of 16.7 at theta of 0. These data indicate that most or all of CF is due to an abnormality at a single locus and that the DNA markers are useful for prenatal diagnosis and heterozygote detection within affected families.

Cystic Fibrosis↗

Changes with time in Langerhans cell number, ATPase reactivity and morphology in murine epidermis after exposure to UVB.

Effects on Langerhans cells of a single 200 mJ/cm2 dose of 284-316 nm UVB were studied in the dorsal epidermis of CBA/H mice. ATPase-positive cells were counted using light microscopy and compared with numbers of cells containing Birbeck granules. In interfollicular epidermis from untreated mice 633 +/- 20 (mean +/- S.E., n = 30) ATPase-positive cells/mm2 were found. By 3 days after UVB treatment, the number of ATPase-positive cells decreased by 90%, whilst the Birbeck granule-containing cell population was only reduced by 40% and very few cells had ultrastructural damage, suggesting that many Langerhans cells lost ATPase marker but remained intact. 7 d after irradiation there were 50% more cells with Birbeck granules than in controls, but the number of cells bearing ATPase remained below normal. ATPase-positive cell numbers approached normal only after a further 2-3 weeks. Langerhans cell responses after UVB differed from those previously found after X-irradiation.

Adenosine Triphosphatases↗

Nucleotide sequence of the AIDS virus, LAV.

The complete 9193-nucleotide sequence of the probable causative agent of AIDS, lymphadenopathy-associated virus (LAV), has been determined. The deduced genetic structure is unique: it shows, in addition to the retroviral gag, pol, and env genes, two novel open reading frames we call Q and F. Remarkably, Q is located between pol and env and F is half-encoded by the U3 element of the LTR. These data place LAV apart from the previously characterized family of human T cell leukemia/lymphoma viruses.

Acquired Immunodeficiency Syndrome↗

Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus.

We have determined the complete 9202 nucleotide sequence of the visna lentivirus. The deduced genetic organization most closely resembles that of the AIDS retrovirus in that there is a novel central region separating pol and env. Moreover, there is a close phylogenetic relationship between the conserved reverse transcriptase and endonuclease/integrase domains of the visna and AIDS viruses. These findings support the inclusion of the AIDS virus in the retroviral subfamily Lentivirinae.

Acquired Immunodeficiency Syndrome↗

Beta blocker overdose with propranolol and with atenolol.

During a one-month period, two cases of beta-adrenergic blocker overdose were treated by the emergency staff at our hospital. One case of propranolol intoxication demonstrated profound cardiovascular collapse and generalized tonic-clonic seizures. The condition failed to respond to high-dose intravenous pressor agents, but did improve significantly with IV glucagon infusion. The second overdose involved atenolol. Although the blood levels reported were very high, the patient showed no cardiovascular compromise and required only inhaled bronchodilators for an exacerbation of her asthma.

Adolescent↗

Plate atelectasis.

Postmortem examination was performed in 15 patients who had plate atelectasis (PA) on their last antemortem radiograph. In 10 patients, corresponding abnormalities were found in the lungs. In all 10, there was peripheral subpleural linear collapse combined with invagination of the overlying pleura; prominent interlobular septa were observed within or bordering the linear atelectasis in nine. The atelectasis and the invaginated pleura both contributed to the linear radiographic density. The bronchi supplying the areas of PA showed no obstruction nor rearrangement. Despite a frequent association with pulmonary embolism (6/10), there was no evidence that PA directly represented thrombosed vessels or infarcts. The findings suggest that PA represents one (radiographically visible) form of peripheral atelectasis. In persisting low-volume states, the dependent subpleural lung appears to buckle and fold in. The frequent association of PA with congenital pleural clefts, indentations, scars, and incomplete fissures suggests that this process may preferentially occur at sites of pre-existing pleural invagination. PA frequently indicates more widespread peripheral atelectasis than is radiologically apparent; it also may indicate the presence of some other (more serious) abnormality in the chest or abdomen.

Aged↗

Dose response of Langerhans cells in mouse footpad epidermis after X irradiation.

Effects of a range (2-50 Gy) of single doses of 250 kV X rays on epidermal Langerhans cells in vivo were quantified in groups of CBA/CaH mice. Animals were sacrificed and compared with controls on the 10th day after local irradiation of their hind feet, when Langerhans cell numbers were at a minimum. ATPase-positive Langerhans cells in sheets of footpad epidermis were counted by light microscopy and cells with Birbeck granules were enumerated by electron microscopy. Both methods revealed a dose-dependent loss of Langerhans cells after ionizing radiation. Fifty percent of the ATPase-positive cells were lost after 14.4 +/- 1.3 Gy, and 50% of Birbeck granule-containing cells were lost after 17.9 +/- 4.2 Gy, suggesting that differentiated epidermal Langerhans cells are radioresistant. Loss of equivalent proportions of ATPase-positive and ultrastructurally identifiable cells after a range of doses indicates that X rays do not merely alter Langerhans cell surface markers but actually deplete the epidermal population of these cells.

Animals↗

Spina bifida and anencephaly in Scotland.

Data obtained from routine sources showed that from 1971 to 1982 the birth prevalences of spina bifida and anencephaly in Scotland fell. When known terminations after routine alpha fetoprotein screening were added to total births the adjusted birth prevalence could be calculated. In 1974-82 this fell by 40% for spina bifida (3 X 0-1 X 8) and 36% for anencephaly (2 X 2-1 X 4). These findings were compared with data on birth prevalences in England and Wales, Northern Ireland, and Glasgow. The fall in birth prevalences of spina bifida and anencephaly over the past decade appears to have been due both to a true fall in incidence as well as to increased screening and termination for these conditions.

Anencephaly↗