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Biomedical subjects

D Page

Publications and source records attributed to D Page.

At least 19 recordsLinked to original sources

Immunotoxicological profile of morphine sulfate in B6C3F1 female mice.

This study was undertaken to investigate a number of immune parameters which may be compromised with exposure to morphine sulfate. Mice were implanted subcutaneously with 8-, 25-, or 75-mg morphine sulfate pellets. Placebo pellets of identical makeup to the 75-mg morphine pellet (without morphine of course) were used as a control. Twenty-four hours after implantation of a 75-mg morphine pellet, blood levels reached a peak of 1610 ng/ml. Corticosterone increased in parallel with morphine and reached a peak level of 966 ng/ml 24 hr after implantation. The dose response of morphine to increase corticosterone, however, was flat. The weight of the lymphoid organs, spleen and thymus, and the liver were significantly reduced in the morphine-treated groups. Morphine treatment was associated with an increase in serum albumin, SGPT, BUN, and alkaline phosphatase indicative of hepatic damage. In contrast to increased serum proteins, the C3 component of complement was reduced in a dose-dependent manner. Leukocyte number in the peripheral blood was significantly reduced, while erythrocyte number and hematocrit were both increased. The number of B cells and T cells was decreased in morphine-treated animals. However, the percentage of T cells relative to B cells was increased. The primary IgM antibody response to the T-dependent antigen, sheep red blood cells, was decreased. Natural killer cell activity was reduced in response to morphine, as was the phagocytic capacity of Kupffer cells. Host-resistance models of Listeria monocytogenes or Streptococcus pneumoniae showed an increased resistance following administration of morphine. This increased host resistance, however, was not due to an increase in antimicrobial action of sera obtained from mice treated with morphine. The majority of morphine's effects on the immune system exhibited a flat dose response, suggesting that these effects may be mediated secondarily through corticosterone.

Animals

Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation.

Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.

Adenoma

Attenuation of monochromatic X-rays by normal and abnormal breast tissues.

RATIONALE AND OBJECTIVES: A prior study indicated that differences in the x-ray linear attenuation coefficients of cancerous and normal breast tissues tend to increase as the energy of the incident beam decreases. The authors investigated x-ray energies down to 20 keV. In the current study, the linear attenuation coefficients for normal and selected cancerous breast tissues within the energy range of 14 to 18 keV were determined. METHODS: Fifty breast biopsy specimens consisting of a mixture of breast malignancies, normal tissues, fat specimens, and tumors grown in rats were used. X-ray linear attenuation coefficients were measured for each sample within the energy range of 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory. Each sample was measured at 130 different energies starting at 14.15 keV with step sizes of 0.030 keV. Correlation of the measured attenuation coefficients for cellular makeup was performed. RESULTS: The mean of linear attenuation coefficients for samples classified as "cancers" was 10.9% higher than the mean of samples classified as "normal" breast tissues and was 66.5% higher than the mean of samples classified as normal breast fat. CONCLUSIONS: Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.

Biopsy

An update on the diagnosis and management of pediatric asthma. Based on the National Heart, Lung and Blood Institute expert panel report.

Asthma morbidity and mortality are increasing despite the availability of antiasthma medicines and a broader understanding of the pathology of the disease. In an attempt to enhance the understanding of asthma and to aid in appropriate asthma management, the National Heart, Lung and Blood Institute assembled an expert panel, which developed a report titled "Guidelines for the Diagnosis and Management of Asthma." These guidelines are designed to facilitate patient and health-care-provider education, and diagnosis and management of asthma. Proper diagnosis of the disease is a frequent problem in children and adults. For proper diagnosis of asthma, a complete patient history, physical examination and specific laboratory tests are required. Health care providers who educate patients and their families about common symptom triggers, encourage avoidance techniques and who incorporate state-of-the-art treatment for acute and chronic asthma management may reduce the recent increases in asthma morbidity and mortality while maintaining normal growth and development of the child.

Academies and Institutes

Early detection of breast carcinoma: a comparison of palpable and nonpalpable lesions.

A retrospective study of 536 needle-localization biopsies of nonpalpable breast lesions and 623 excisional biopsies of palpable breast lesions was performed. Carcinoma was present in 17.9% of needle-localization biopsy specimens and in 11.1% of excisional biopsy specimens. Noninvasive carcinoma constituted 50% of carcinomas detected by needle-localization biopsy and only 7.3% of carcinomas detected by excisional biopsy (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was associated with axillary lymph node metastasis in 9.8% of patients who had axillary dissection, compared with 37.7% of patients with invasive carcinoma detected by excisional biopsy of a palpable mass (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was less than 2 cm in size (T1) in 93.5% of biopsy specimens; in contrast, invasive carcinoma detected by excisional biopsy was less than 2 cm in size in only 54.7% of biopsy specimens (p less than 0.005). Nonpalpable breast lesions that proved to be invasive carcinoma were pathologic stage I in 82.9% of patients. Palpable breast lesions that proved to be invasive carcinoma were pathologic stage I in only 47.2% of patients. Survival benefits of mammographic screening and biopsy of nonpalpable lesions are likely the result of detection of invasive carcinoma at an early stage and detection of noninvasive carcinoma that may later develop into or mark increased risk of invasive carcinoma.

Axilla

Characterization of novel platelet and endothelial cell target antigens in a family with genetic susceptibility to autoimmunity.

This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.

Antigens, CD

Genetic mapping in the region of the mouse X-inactivation center.

The mouse X-inactivation center lies just distal to the T16H breakpoint. Utilizing pedigree analysis of backcross progeny from a Mus domesticus/Mus spretus interspecific cross, we have mapped a number of genetic loci, gene probes, microclones, and EagI linking clones distal to the T16H breakpoint. The genetic analysis provides a detailed genetic map in the vicinity of the mouse X-inactivation center. Comparative mapping data from the human X chromosome indicate that the most probable location of the mouse X-inactivation center is distal to Ccg-1 and in the region of the Pgk-1 locus. We report the assignment of two new loci, EM13 and DXSmh44, to the Ccg-1/Pgk-1 interval.

Animals

Haplotype and multipoint linkage analysis in Finnish choroideremia families.

Multipoint linkage analysis of choroideremia (TCD) and seven X chromosomal restriction fragment length polymorphisms (RFLPs) was carried out in 18 Finnish TCD families. The data place TCD distal to PGK and DXS72, very close to DXYS1 and DXYS5 (Zmax = 24 at theta = 0) and proximal to DXYS4 and DXYS12. This agrees with the data obtained from other linkage studies and from physical mapping. All the TCD males and carrier females studied have the same DXYS1 allele in coupling with TCD. In Northeastern Finland, 66/69 chromosomes carrying TCD had the same haplotype at loci DXS72, DXYS1, DXYS4, and DXYS12. The same haplotype is seen in only 15/99 chromosomes not carrying TCD. Moreover, in 71/104 non-TCD chromosomes, the haplotype at six marker loci is different from those seen in any of the 76 TCD chromosomes. This supports the previously described hypothesis that the large Northern Finnish choroideremia pedigrees, comprising a total of over 80 living patients representing more than a fifth of all TCD patients described worldwide, carry the same mutation. These linkage and haplotype data provide improved opportunities for prenatal diagnosis based on RFLP studies.

Choroideremia

Suppression of humoral immune responses by dialkylnitrosamines: structure-activity relationships.

Comparisons between chemical structure of N,N-dialkylnitrosamine congeners and their ability to alter the Day 4 IgM antibody response to sRBC, body weights, and organ weights of female B6C3F1 mice were investigated. Short-chain nitrosamine congeners were selected for these studies on the basis of two criteria: (1) congeners with symmetrical aliphatic chain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine (DEN), N-nitrosodipropylamine (DPN), N-nitrosodibutylamine (DBN)] and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine (MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine (MBN)]. The immunotoxicity of each congener was evaluated based on the compound's ability to suppress the in vivo sRBC antibody response following 7 consecutive days of treatment. An ED50 dose was calculated, using a linear regression analysis, for each congener and represents the millimoles of congener per kilogram body weight required to cause a 50% suppression of the sRBC response. These studies demonstrated two general trends: (1) those dialkylnitrosamine congeners that possessed an N-methyl group were most immunotoxic and exhibited comparable ED50 concentrations (42-183 mumol/kg); and (2) dialkylnitrosamine congeners possessing symmetrical aliphatic chains demonstrated an inverse relationship between aliphatic chain length and immunotoxic potency--DMN (62 mumol/kg) greater than DEN (276 mumol/kg) greater than DPN (467 mumol/kg) greater than DBN (1557 mumol/kg). Comparisons were also made between the immunotoxic potency of various nitrosamine congeners in the whole animal and their potency in an in vitro hepatocyte-spleen cell coculture system.

Animals

Short-term effects of various phenols and acids on the Fischer 344 male rat forestomach epithelium.

A series of phenols and acids was fed to rats for 9 days to determine effects on the [methyl-3H]thymidine labelling index and the histological appearance of the forestomach. A variety of proliferative effects in the rat forestomach were observed which paralleled changes in the [methyl-3H] thymidine labelling index. The 3-tert-butyl isomer of butylated hydroxyanisole (BHA) was as effective as the food grade mixture. In the 4-hydroxybenzoic acid ester series, activity was not found either with the free acid or the methyl ester. With the ethyl, n-propyl and n-butyl esters activity in the perfundic region of the forestomach increased with alkyl chain length, the n-butyl ester being nearly as effective as BHA. In contrast, 4-methoxyyphenol and propionic acid demonstrated their greatest effects in the midregion of the forestomach, the action of propionic acid not being apparent until 21 or 27 days of treatment. It was also found that after a 9-day treatment involving coadministration of BHA and acetylsalicyclic acid, the overall effect of the antioxidant on the forestomach was greatly reduced.

Animals

Splenic abscess following nonoperative management of splenic rupture.

A recent case of posttraumatic splenic abscess in a young man following nonoperative management of his splenic rupture is reported. With the recent trend toward nonoperative management of hemodynamically stable splenic rupture, the potential complications of splenic abscess may become more common. In view of the high mortality associated with unrecognized splenic abscess, it is important for the clinician to be aware of this entity.

Abscess

Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

Amino Acid Sequence