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Biomedical subjects

W L Marsh

Publications and source records attributed to W L Marsh.

At least 37 records · Page 2Linked to original sources

Sextant prostate biopsies. A histopathologic correlation with radical prostatectomy specimens.

BACKGROUND: Among patients with clinically localized prostate cancer, preoperative prediction of tumor volume and pathologic stage has been unreliable. This study examines the application of transrectal ultrasound-guided sextant biopsies to predict the extent of disease. METHODS: One hundred and two patients with clinically resectable prostate cancer were evaluated by systematic sextant biopsies. Radical prostatectomy specimens were embedded totally as whole mounts, tumor areas were outlined, and volume was measured using a digital scanner. The number of positive sextant biopsies was compared with age, race, preoperative prostate specific antigen (PSA), PSA density, DNA ploidy, pathologic stage, capsular and seminal vesicle involvement, prostate and tumor volume, and Gleason score. Stepwise logistic regression was used to determine if pathologic stage or tumor size could be predicted by these parameters. RESULTS: The number of positive sextant biopsies correlated with traditional prognostic indicators. When patients with three or fewer positive biopsies were compared with those with four or more positive sextant biopsies, significant differences were identified relative to preoperative PSA (P < 0.001), tumor volume (P < 0.001), pathologic stage (P < 0.001), Gleason score (P < 0.001), seminal vesicle involvement (P < 0.001), and capsular penetration (P < 0.001). There were no significant differences based on age, race, DNA ploidy, and overall prostate volume. Logistic regression showed that patients with four or more positive sextant biopsies and high Gleason score had a greater likelihood of pT3 classification. Likewise, the probabilities of a tumor volume less than 0.5 ml could be predicted by the number of positive sextant biopsies and PSA alone. The number of positive sextant biopsies was the only factor that could predict a tumor volume greater than 4.0 ml. CONCLUSION: The number of positive sextant biopsies appears to be an important prognostic indicator of pathologic (pT) classification and tumor volume. This information is valuable in selecting the treatment strategy for patients with prostate cancer.

Age Factors↗

Sydenham's chorea: magnetic resonance imaging of the basal ganglia.

Analysis of cerebral magnetic resonance images of 24 subjects with Sydenham's chorea and 48 age-, height-, weight-, gender-, and handedness-matched controls demonstrated increased sizes of the caudate, putamen, and globus pallidus in the Sydenham's chorea group. In contrast, neither total cerebral, prefrontal, or midfrontal volumes or thalamic area were increased. These results indicate the selective involvement of the basal ganglia in Sydenham's chorea.

Adolescent↗

Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder.

OBJECTIVE: Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wide age range was sampled for both groups. METHOD: The brains of 50 male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T1-weighted coronal images. Interrater reliabilities (intraclass correlations) were 0.89 or greater. RESULTS: The normal pattern of slight but significantly greater right caudate volume across all ages was not seen in ADHD. Mean right caudate volume was slightly but significantly smaller in the ADHD patients than in the comparison subjects, while there was no significant difference for the left. Together these facts accounted for the highly significant lack of normal asymmetry in caudate volume in the ADHD boys. Total brain volume was 5% smaller in the ADHD boys, and this was not accounted for by age, height, weight, or IQ. Smaller brain volume in ADHD did not account for the caudate volume or symmetry differences. For the normal boys, caudate volume decreased substantially (13%) and significantly with age, while in ADHD there was no age-related change. CONCLUSIONS: Along with previous MRI findings of low volumes in corpus callosum regions, these results support developmental abnormalities of frontal-striatal circuits in ADHD.

Adult↗

The human Kell blood group gene maps to chromosome 7q33 and its expression is restricted to erythroid cells.

The Kell blood group is one of the major antigenic systems in human red blood cells. To determine the location of the Kell gene on human chromosomes, panels containing genomic DNA of human-hamster somatic cell hybrids were hybridized with radiolabeled cDNA probe specific for the Kell locus. Only the samples containing DNA from chromosome 7 gave positive hybridization signals. In situ hybridization analysis, using genomic clones isolated with the cDNA, localized the KEL gene to 7q33. Northern blot analysis of poly(A)+ RNA from human brain, kidney, lung, fetal and adult liver, and bone marrow showed that Kell transcripts were only present in fetal liver and bone marrow. This indicates that the Kell protein, which carries the Kell antigens, may only be expressed in erythroid tissues.

Animals↗

Molecular cloning and primary structure of Kell blood group protein.

The Kell blood group is a major antigenic system in human erythrocytes. Kell antigens reside on a 93-kDa membrane glycoprotein that is surface-exposed and associated with the underlying cytoskeleton. We isolated tryptic peptides and, based on the amino acid sequence of one of the peptides and by using the PCR, prepared a specific oligonucleotide to screen a lambda gt10 human bone-marrow cDNA library. Four clones were isolated, one containing cDNA with an open reading frame for an 83-kDa protein. All known Kell amino acid sequences were present in the deduced sequence; moreover, rabbit antibody to a 30-amino acid peptide, prepared from this sequence, reacted on an immunoblot with authentic Kell protein. The Kell cDNA sequence predicts a 732-amino acid protein. Hydropathy analysis indicates a single membrane-spanning region, suggesting that Kell protein is oriented with 47 of its N-terminal amino acids in the cell cytoplasm, and a 665-amino acid segment, which contains six possible N-glycosylation sites, is located extracellularly. Computer-based search showed that Kell has structural and sequence homology to a family of zinc metalloglycoproteins with neutral endopeptidase activity.

Amino Acid Sequence↗

Nonpigmented papillary carcinoma in a black thyroid gland.

A case of papillary thyroid carcinoma occurring in a 27-year-old man with black thyroid syndrome is reported. The tumor, in contrast to the remaining thyroid, was not pigmented. The significance and potential utility of the differential pigmentation are discussed.

Adult↗

Poorly differentiated ('insular') thyroid carcinoma. Report of two cases and review of the literature.

The clinical, histopathologic, immunohistochemical, and electron microscopic findings of two cases of poorly differentiated ("insular") thyroid carcinoma are reported and compared with the 25 cases previously described in the literature. These 27 cases occurred in eight men and 19 women, aged from 34 to 77 years. All but 2 presented with a thyroid mass. Eleven (41%) of the 27 patients experienced local recurrences following surgery, 17 (63%) had development of cervical lymph node metastases, 5 (19%) had development of mediastinal lymph node metastases, 11 (41%) had pulmonary metastases, and 9 (33%) had bone metastases, and 9 (33%) had bone metastases. At least 15 patients (56%) are known to have died of their disease, usually within 8 years of diagnosis. Pathologically, the tumors are distinctive and grow as solid islands (insulae) of small cells separated by artifactually created clefts. In some instances, small follicles are also noted within the insulae. All tumors were positive on immunostaining for thyroglobulin. In view of the propensity for local recurrences and lymphatic and hematogenous dissemination, a total thyroidectomy and neck dissection would seem advisable. Additionally, adjuvant external beam irradiation, systemic chemotherapy, and/or radioactive iodine therapy should also be considered.

Adenocarcinoma↗

Abnormal membrane physical properties of red cells in McLeod syndrome.

McLeod red cells (RBCs) lack Kx antigens and have weak expression of the Kell antigens. Individuals who carry the McLeod phenotype have acanthocytic RBCs and a compensated hemolytic state. To elucidate the role of the protein on which the Kx antigens reside in maintaining membrane deformability, the rheologic properties of McLeod RBCs were determined by ektacytometry. RBCs were obtained from normal individuals and from four patients with McLeod syndrome. Osmotic gradient deformability profiles of McLeod RBCs showed decreased whole cell deformability. Resealed ghosts from McLeod RBCs also showed decreased deformability, partly because of the decreased cell surface area and partly because of an intrinsic membrane stiffness in this syndrome. For the measurement of membrane mechanical stability, resealed ghosts were subjected to constant high shear stress in the ektacytomer, and deformability was recorded continuously as the deformable ghosts fragmented into rigid spherical vesicles. Membranes from McLeod RBCs showed a noticeable increase in mechanical stability. Acquired causes of acanthocytosis, such as liver disease, did not cause the rheologic abnormalities observed in McLeod cells. Other abnormalities noted in McLeod RBCs were decreased RBC potassium content and an increased number of dense RBCs, as determined by centrifugation on a discontinuous density gradient. The data indicate that McLeod RBCs are rigid and have decreased surface area and that their membranes are intrinsically rigid with increased mechanical stability. These abnormalities may account for the reduced RBC survival observed in McLeod syndrome. The protein that carries the Kx surface antigen seems to be required for the maintenance of the normal physical function of RBC skeletal proteins.

Adult↗

Hairy cell leukemia involving an inguinal hernial sac.

A 37-year-old man with hairy cell leukemia was found incidentally to have a right inguinal hernia. Microscopic examination of the resected herniorrhaphy specimen disclosed dense transmural infiltration by hairy cells. Electron-microscopic and immunoperoxidase studies confirmed the presence of surface cytoplasmic projections and B cell phenotype, respectively, of the infiltrating cells. This case is, to our knowledge, the first reported instance of hairy cell leukemia involving a hernial sac and demonstrates the capacity of hairy cells to infiltrate unexpected soft-tissue sites.

Adult↗

Diffuse angiomatosis of the extremities presenting as a sarcoma.

Diffuse angiomatosis of the extremities is a rare condition characterized by extensive or multifocal benign mass-forming vascular lesions involving multiple tissue planes; histologically, adipose and fibrous tissue are admixed with vascular elements that vary from capillary proliferations to large vessels that are often structurally abnormal. Although diffuse angiomatosis most likely represents a hamartomatous form of arteriovenous malformation, it behaves clinically as a benign but slowly progressive and unresectable neoplasm. We describe a case of diffuse angiomatosis of the lower extremity that presented clinically as a soft-tissue sarcoma.

Angiomatosis↗

Purification and characterization of an erythrocyte membrane protein complex carrying Duffy blood group antigenicity. Possible receptor for Plasmodium vivax and Plasmodium knowlesi malaria parasite.

A murine monoclonal antibody, named anti-Fy6, which agglutinates all human red cells except those of Fy(a-b) phenotype was used for purification and characterization of Duffy antigens. Duffy antigens are multimeric red cell membrane proteins composed of different subunits of which only one, designated pD protein, reacts in immunoblots with the murine monoclonal antibody anti-Fy6. Affinity-purified detergent-soluble antigen-antibody complex obtained from red cells, surface-labeled with 125I yielded a complex pattern of bands when separated by polyacrylamide gel electrophoresis. Proteins that react with anti-Fy6 in immunoblots are: pA and pB (greater than 100 kDa) and pD (36-46 kDa). Electroeluted pD protein aggregates and generates bands of similar molecular mass to pA and pB proteins. Electroeluted pA and pB proteins disaggregate yielding pD protein. Oligomers and monomers of pD protein are present in red cells carrying Duffy antigens and absent in Fy(a-b-) cells. Six other proteins of molecular weight ranging from 68 to 21 kDa either associate or co-purify with pD protein. These proteins are only present in Duffy antigen positive cells. The pD protein is different in Fy(a+b-) and Fy(a-b+) cells by fingerprint analysis. Human antisera identify the same proteins in red cell carrying Duffy antigens as the murine monoclonal antibody anti-Fy6.

Animals↗

The Kmod blood group phenotype in a healthy individual.

This report describes a healthy blood donor whose red cells have weakened expression of Kell blood group antigens. Kell antigen activity could not be detected by flow cytometric analysis and was demonstrable only by sensitive serologic techniques. As with normal-strength Kell antigens, reactivity could be abolished by treatment with 2-aminoethylisothiouronium bromide (AET). The donor's red cells have Kx antigen activity. Other commonly tested blood group antigens (MNSs, Rh, P1, Lewis, Duffy, and Kidd systems) appear normal. Clinical and serologic examination showed that this case is different from previously described examples of modified Kell expression. The propositus's phenotype has remained unchanged for 19 months, which suggests that it is not a transient condition. However, family studies provide no evidence that it is inherited. A 93-kD protein, which reacted weakly by Western blot with rabbit antibody to Kell protein, was isolated from the propositus's red cells by immunoprecipitation. This finding was not reproduced in subsequent studies, which suggests that the quantity of Kell protein recovered was at the threshold level detectable by the technique used. The red cell phenotype is categorized as Kmod, of which this is the first example reported in a healthy individual.

Absorption↗

Hyperreactio luteinalis. Benign disorder masquerading as an ovarian neoplasm.

Hyperreactio luteinalis (HL) refers to moderate to marked cystic enlargement of the ovaries due to multiple benign theca lutein cysts and is most often associated with hydatidiform mole or choriocarcinoma. The cause of this condition is unknown, but is believed to be related to elevated levels of, or abnormal ovarian response to, human chorionic and pituitary gonadotropins. Only 47 cases of HL unassociated with trophoblastic disease have been previously reported in the English-language literature, mostly before 1974, and almost exclusively in the gynecologic literature. We present two additional cases of HL unassociated with trophoblastic disease and review the literature. One of our case reports documents the unusual occurrence of unilateral HL. Of the 49 cases described, 11 occurred with fetal hydrops (8 immunologic; 3 non-immunologic), 8 with multiple pregnancies, and 30 in otherwise normal single pregnancies. Hyperreaction luteinalis is most often bilateral and found incidentally at the time of cesarean section. However, HL may present during any trimester as an abdominal mass or acute abdomen. The natural course is postpartum regression. Recognition of HL is important, since misinterpretation at laparotomy or erroneous histologic diagnoses have resulted in unnecessary surgery, often with sterilization in 16 of the cases. A conservative approach is indicated with wedge biopsy and frozen section diagnosis. Oophorectomy is necessary only to remove infarcted tissue or to control hemorrhage.

Adult↗

Chondrolipoma of the breast.

Benign cartilage-containing mesenchymal tumors of the breast are extremely rare. We describe a patient with chondrolipoma of the breast who presented with a breast mass that was detected by routine mammography. Although the mammographic features of chondrolipoma are not specific, the histologic features are diagnostic and show a well-circumscribed mass composed of benign adipose tissue and lobules of mature cartilage. We also discuss the differential diagnosis of benign mesenchymal tumors of the breast.

Breast Neoplasms↗