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Biomedical subjects

J H Beckstead

Publications and source records attributed to J H Beckstead.

At least 55 records · Page 3Linked to original sources
PubMed1987

Leu-M1 antigen as a marker of acute nonlymphoid leukemia.

The monoclonal antibody Leu-M1 was originally described as a marker of myeloid/monocytic cells and their precursors. Its usefulness as a myeloid marker in bone marrow specimens was further supported by a limited number of studies using flow cytometry and cell suspensions. Recent reports on its utility in paraffin sections for the diagnosis of acute leukemia have not shown it to be an effective marker of myeloid differentiation. To further evaluate the diagnostic usefulness of Leu-M1 in acute leukemia, we investigated the immunoreactivity of Leu-M1 antigen in a series of 100 plastic-embedded bone marrow biopsies from patients with acute leukemia and compared these results to those obtained in a series of 30 paraffin-embedded specimens. We also investigated the usefulness of neuraminidase pretreatment of sections to enhance the sensitivity of Leu-M1. In plastic sections, we were able to demonstrate positive Leu-M1 staining in 48 of 50 (96%) cases of acute nonlymphoid leukemia (ANL) (FAB classification M1-M5) and 0 of 50 cases of acute lymphocytic leukemia (ALL). Comparatively, Leu-M1 stained positively in 10 of 20 (50%) cases of ANL and 0 of 10 ALL embedded in paraffin. In both plastic and paraffin sections, pretreatment with neuraminidase enhanced the sensitivity of Leu-M1 reactivity, but markedly decreased its specificity. Our study suggests Leu-M1 is both a reliable marker of myelomonocytic differentiation and a useful diagnostic tool in the differentiation of ANL from ALL in plastic sections, and confirms its limited usefulness in paraffin-embedded material.

Antibodies, Monoclonal↗
PubMed1987

An ultrastructural and histochemical study of the prominent inflammatory response in D(+)-galactosamine hepatotoxicity.

The biochemical basis of the hepatitis-like liver injury produced by D(+)-galactosamine in rats is well-established and is linked to depletion of uridine nucleotides within parenchymal cells. However, the prominent inflammatory response that accompanies this lesion in vivo has been largely overlooked as a component of the hepatic damage. This study examines the cellular components of the inflammatory infiltrate of galactosamine-induced liver injury over time using histochemical and ultrastructural techniques. By 12 h after toxin administration, the infiltrate consisted largely of neutrophils and recently-mobilized monocytes. By 24 to 48 h after the toxin, when hepatocellular necrosis was maximal, few neutrophils were found in the infiltrate. At these times, the infiltrate consisted almost exclusively of large phagocytic cells, histochemically and morphologically consistent with active tissue macrophages apparently derived from circulating monocytes. The extent of the inflammatory response to this experimental hepatotoxin suggests that effects on the generation and development of the inflammatory response should be considered for treatments reported to alter the intrinsic hepatotoxicity of galactosamine.

Acid Phosphatase↗
PubMed1987

Influence of training and experience in fine-needle aspiration biopsy of breast. Receiver operating characteristics curve analysis.

In an effort to assess the influence of training and experience on the interpretation of fine-needle aspiration biopsy (FNAB) specimens, five observers with varying degrees of training and experience reviewed a series of 50 breast FNAB specimens. The cases selected were from the cytology registry of the University of California, San Francisco; all cases necessarily had histologic follow-up. By using receiver operating characteristics analysis, we were able to show that training and experience significantly influenced the interpretation of breast FNAB specimens. The two experts operated at a higher level of sensitivity and specificity than did three nonexperts. This study shows that training and experience are important in the interpretation of breast FNAB specimens. It also demonstrates the utility of receiver operating characteristics analysis in anatomic pathology.

Biopsy, Needle↗
PubMed1986

Primary central nervous system lymphoma in acquired immune deficiency syndrome: a clinical and pathological study.

Twenty cases of primary lymphoma of the central nervous system associated with acquired immune deficiency syndrome were seen over a period of four years and were studied clinically and pathologically. Biopsy established the diagnosis in 11 cases, and autopsy confirmed it in 9. Multicentricity was demonstrated in all cases for which there was adequate autopsy material. Both large-cell immunoblastic and small noncleaved lymphomas were seen, and marker studies in 5 patients established that the lymphomas were of B-cell origin. Neurological symptoms and signs, cerebrospinal fluid characteristics, and radiographic appearance were reviewed. The clinical and radiographic picture is nonspecific and histological confirmation is essential for diagnosis. Although the tumor appears to be radiosensitive, prognosis is extremely poor, with an average survival of less than two months.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Leu-6-expressing cells in lymph nodes: dendritic cells phenotypically similar to interdigitating cells.

Leu-6 is an antigen expressed by immature T cells, Langerhans cells, and indeterminate cells, the latter two of which are dendritic cells found predominantly within the skin. In dermatopathic lymphadenopathy, the paracortex is expanded by T cells and dendritic cells, including Langerhans cells. While the paracortex also contains Leu-6+ cells, the nature of such cells in lymph nodes has been controversial. To determine the characteristics of Leu-6+ paracortical cells, their morphologic, antigenic, and enzymatic features were studied in lymph nodes showing dermatopathic lymphadenopathy or reactive follicular hyperplasia. Immunologic studies with plastic, frozen, and paraffin sections demonstrated a dendritic cell morphology, a dendritic cell lineage phenotype (L3B12+, HLA-A,B,C+, HLA-DR+, S-100+), and the absence of T-cell lineage phenotype. These findings were corroborated by the enzymatic phenotype of these cells observed in plastic sections (membrane ATPase+, weak paranuclear acid phosphatase+, weak paranuclear alpha-napthylacetate esterase+). Although all paracortical dendritic cells were otherwise identical, only a subset of these cells were Leu-6+. The close phenotypic similarity between these Leu-6+ and Leu-6- paracortical dendritic cell subsets suggests a close ontogenetic relation. Furthermore, the greater abundance of the Leu-6+ subset in dermatopathic lymph nodes than in nodes exhibiting only reactive follicular hyperplasia, in conjunction with the presence of Leu-6+ dendritic cells within the sinuses of dermatopathic lymph nodes, suggests that at least some of the paracortical Leu-6+ cells are Leu-6+ Langerhans cells or indeterminate cells derived from the skin via the afferent lymphatics.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Enzyme histochemistry and thyroid neoplasia.

The authors have examined the enzyme histochemical staining of surgically removed human thyroid tissue in an attempt to identify markers that might be useful in the histopathologic diagnosis of thyroid neoplasms. Fresh thyroid glands and other tissues were fixed in cold (4 degrees C) 4% paraformaldehyde and embedded in glycol methacrylate. Forty-two specimens were studied in thin sections, which gave excellent histologic detail and enzyme preservation. Cytologic detail was similar to that in Papanicolaou-stained smears, with good definition of nuclear inclusions and grooves, particularly in cases of papillary carcinoma. The enzyme histochemical reactions studied were as follows: adenosine triphosphatase, alkaline and acid phosphatases, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Thyroid epithelial cells and the benign neoplasms derived from them were typically positive for 5'-nucleotidase, alpha-naphthyl acetate esterase, and acid phosphatase, and negative for adenosine triphosphatase and alkaline phosphatase. Staining for adenosine triphosphatase was present in papillary and follicular carcinomas and was seen in benign glands only under certain circumstances such as Graves' disease. The adenosine triphosphatase reaction therefore appears to be helpful in distinguishing between benign and malignant neoplasms derived from thyroid epithelium in humans and may be a useful adjunct to routine morphology.

5'-Nucleotidase↗
PubMed1986

Malignant fibrous histiocytoma tumor cells resemble fibroblasts.

The malignant fibrous histiocytomas (MFHs) are a histologically heterogeneous group of sarcomas that have been postulated to be derived from, or have the capacity to differentiate into, histiocytes. To determine whether MFH tumor cells actually express the features of histiocytes, i.e., bone marrow-derived cells of monocyte-macrophage lineage, we studied the antigenic and enzymatic phenotype of 13 MFHs in situ using frozen and plastic sections, respectively. Five pleomorphic three fibrous, two myxoid, two giant cell, and one histiocytic MFH were studied. While tumor cells in 12 of 13 cases were positive for HLA-A,B,C, tumor cells in all cases failed to express antigens present on bone marrow-derived macrophages, i.e., leukocyte common antigen (L3B12), HLA-DR, Leu-M3, and Leu-3a. Interestingly 8 of 13 cases were positive for CALLA. Although nonspecific, this may prove useful in differential diagnosis. Enzyme histochemistry demonstrated that tumor cells in 9 of 13 cases were positive for membrane 5' nucleotidase (5'N+). Four of these were also alkaline phosphatase positive (ALKP+). All cases were either negative or weakly positive for acid phosphatase (ACIDP) and alpha-naphthyl acetate esterase (ANAE). Tumor cells were unreactive for alpha-naphthyl butyrate esterase (ANBE) and adenosine triphosphatase (ATP). These findings indicate that MFH tumor cells do not express the enzymatic profile of cells of monocyte/macrophage lineage which are membrane 5'N-/ALKP- and ACIDP+/ANAE+/ANBE+/ membrane ATP+. In fact, these data suggest a similarity to fibroblasts which are membrane 5'N+, variably ALKP+, weakly ACIDP+/ANAE+, and ANBE-/membrane ATP-. Osteoclast-like giant cells present in two cases did express a histiocytic phenotype, suggesting that they are reactive elements not derived from admixed tumor cells. These results suggest that MFHs are primitive mesenchymal neoplasms, most likely sarcomas composed of poorly differentiated fibroblasts, and are unrelated to true histiocytic neoplasms.

Fibroblasts↗
PubMed1986

Enzyme histochemistry of hepatocellular neoplasms.

We examined a series of hepatocellular neoplasms, including 4 adenomas, 7 hepatoblastomas, and 18 hepatocellular carcinomas (HCC) with enzyme histochemistry in plastic-embedded sections. Our most striking observation was that there was a distinct difference in the staining pattern for alkaline phosphatase (Alk0) in benign and malignant tumors. Non-neoplastic controls (normal liver, reactive lesions) and benign neoplasms showed a distinctive canalicular pattern of staining with Alk0. Malignant neoplasms, however, showed a virtual absence of Alk0 staining; 6 of 7 hepatoblastomas and 17 of 18 HCCs were practically devoid of staining, while the two positive cases showed a pattern easily discernible from normal. The sensitivity of the observed Alk0 staining pattern in detecting malignant hepatocellular neoplasms was 92% and the specificity was 100%. Cytoplasmic gamma-glutamyl-transferase (GGT) was present in a minority of HCCs, but faint staining was also seen in normal liver or in adenomas. It appears that these nonmorphologic techniques may aid the surgical pathologist in the differential diagnosis of primary hepatocellular neoplasms.

5'-Nucleotidase↗
PubMed1986

Preparation of mouse monoclonal antibodies and evidence for a host immune response to the preacetabular gland proteinase of Schistosoma mansoni cercariae.

Forty-six monoclonal antibodies were produced against the preacetabular gland secretions of Schistosoma mansoni cercariae by two different immunization protocols. These antibodies were of both the IgG and the IgM classes. One IgM monoclonal antibody (Ia4D6) was further characterized. It was specific to the cercarial stage by ELISA and showed specific binding to the 30,000 Mr proteinase in crude cercarial secretions by Western blot analysis. Preincubation of this antibody with purified cercarial proteinase resulted in inhibition of proteolytic activity, and it mediated complement-dependent cytotoxicity to cercariae in vitro. Immunoperoxidase staining of cercariae localized this antibody to vesicles visible within the preacetabular glands and their secretory ducts, and to secreted material. ELISA and Western blot analysis also showed that sera from infected mice and patients with schistosomiasis reacted with the cercarial proteinase. These studies demonstrate that a proteinase secreted into the host by invading cercariae is immunogenic and provide a monoclonal antibody probe for further characterization of its structure and function.

Animals↗
PubMed1986

Immunohistochemical localization of membrane and alpha-granule proteins in human megakaryocytes: application to plastic-embedded bone marrow biopsy specimens.

Using a new technique for antigen localization, we have demonstrated platelet proteins in megakaryocytes in plastic-embedded biopsy specimens of normal human bone marrow. In a series of 25 specimens, megakaryocytes showed labeling with antibodies to the integral membrane glycoproteins IIIa, IIb, and the IIb-IIIa complex; granule membrane protein 140; and five alpha-granule matrix proteins: thrombospondin, factor VIII-related antigen, beta-thromboglobulin, platelet factor 4, and fibrinogen. The antibodies to the membrane glycoproteins IIIa, IIb, and IIb-IIIa produced diffuse cytoplasmic staining and heavier staining on the plasma membrane, whereas the antibodies to the alpha-granule matrix proteins produced a distinct granular staining within the cytoplasm. Staining for granule membrane protein 140 was also granular in distribution. Rare mononuclear cells consistent with megakaryocyte precursors were labeled with these markers. Other enzyme histochemical and lectin-binding studies showed that the enzyme alpha-naphthyl acetate esterase, the lectin Ulex europaeus I, and the periodic-acid Schiff reaction were consistent, but not specific, markers of megakaryocytes. This immunohistochemical technique should facilitate the examination of qualitative and quantitative changes in megakaryocytes in a variety of physiologic and pathologic processes.

Antigens↗
PubMed1986

Immunohistochemical localization of membrane and alpha-granule proteins in plastic-embedded mouse bone marrow megakaryocytes and murine megakaryocyte colonies.

Using an immunoperoxidase technique that permits optimal antigen localization at the light microscope level, we have detected two platelet alpha-granule constituents and three platelet membrane glycoproteins in mouse bone marrow megakaryocytes and in murine megakaryocyte colonies grown in soft agar culture for three to seven days. Using polyclonal antibodies prepared against human platelet proteins, we have demonstrated labeling for von Willebrand factor, fibrinogen, and the membrane glycoproteins IIIa and GMP-140 in both bone marrow megakaryocytes and megakaryocyte colonies after seven days of culture. Using monoclonal antibodies to membrane glycoproteins IIb and GMP-140, we have demonstrated label in mouse bone marrow megakaryocytes. Granulocyte and macrophage colonies were negative for each of these markers. Murine bone marrow megakaryocytes and megakaryocyte colonies demonstrated a similar enzyme histochemical pattern: weakly positive for alpha-naphthyl acetate esterase and negative for chloroacetate esterase. These data indicate that megakaryocytes grown in soft agar culture express many of the same glycoproteins as bone marrow megakaryocytes. Furthermore, the ability of antibodies directed against human platelet membrane glycoproteins to identify murine megakaryocyte glycoproteins indicates that these constituents have been highly conserved during evolution.

Animals↗
PubMed1986

The bone marrow biopsy. A diagnostic strategy.

Recent technical advances have dramatically improved the diagnostic information available from a properly prepared bone marrow biopsy specimen. The most important of these is the ability to perform both enzyme histochemical and immunohistochemical procedures on the bone marrow biopsy specimen. These techniques make it possible to apply marker studies to all leukemias, including those with marrows that cannot be aspirated, and to focal lesions that may not be present in aspirated material. This review outlines the optimal use of the bone marrow biopsy as a tool in the evaluation of human bone marrow.

Adult↗
PubMed1985

Enzyme histochemical comparison of biomphalaria glabrata amebocytes with human granuloma macrophages.

In fresh water snails, amebocytes are the principal cells that react to parasitic infection. Ultrastructurally, amebocytes resemble mammalian macrophages. To clarify the relationship between amebocytes and macrophages, we compared the histochemical staining for seven enzymes in Biomphalaria glabrata snail amebocytes, both in the amebocyte-producing organ (APO) and in the encapsulation reaction formed around parasite sporocysts with the staining in macrophages from the lymph nodes of patients with sarcoid or tuberculosis. Snails were infected with Echinostoma paraensei and Schistosoma mansoni miracidia. APOs and ventricular tissue with encapsulated parasites were fixed and embedded in glycol methacrylate monomer. Hardened blocks were sectioned at 2 micron and stained for alkaline phosphatase, acid phosphatase, alpha-naphthyl acetate esterase (ANAE), ATPase, peroxidase, 5'nucleotidase, and chloroacetate esterase. The amebocyte-producing organ contained cells that were positive for acid phosphatase, ANAE, and ATPase. Amebocytes in the capsules formed around echinostome sporocysts showed stronger staining for the same three enzymes. Capsules did not form around schistosome sporocysts, but the connective tissue around them contained numerous amebocytes that were also positive for these three enzymes. The amebocyte enzyme histochemistry resembled that in human granuloma macrophages, but differed from that in neutrophils. The increased expression of enzymes in amebocytes involved in the encapsulation reaction as compared to those in the APO was reminiscent of the alterations observed when human monocytes convert to tissue macrophages. These studies support the hypothesis that the amebocyte is an "invertebrate macrophage."

Acid Phosphatase↗
PubMed1985

Monocyte/macrophage derived cells in normal and transplanted human kidneys.

The existence of HLA-DR/Ia-like antigen (Ia)-bearing cells of the mononuclear phagocyte system, macrophages (Mac), and/or interdigitating cells (IDC), in the normal kidney is controversial. If present, such cells may be important in renal transplant rejection. We performed enzyme histochemistry using alpha-naphthyl acetate/butyrate esterases (alpha NAE, alpha NBE), 5'-nucleotidase (5'N), acid phosphatase (AcP), alkaline phosphatase (AlkP), and ATPase (ATP) as well as immunoperoxidase staining for Ia and lectin binding (Ulex europaeus I; UEA) on plastic-embedded tissue sections of normal kidneys and rejected renal allografts. Plastic embedding provides clear visualization of histologic detail and allows specific identification of immunoperoxidase-stained cells. Mac and IDC (shown to be Ia+, alpha NAE+, AcP+, ATP+ in other sites) could not be demonstrated in normal renal interstitium. IDC and Mac were not generally identified in normal mesangium, although they could not be altogether distinguished from Ia+ endothelial cells. Focal mesangial staining for alpha NAE but not alpha NBE was present. Rejected kidneys showed increased numbers of alpha NAE+ cells in glomeruli. These cells were frequently Ia negative and often appeared to be blood monocytes present in capillary lumens. Peritubular capillaries and glomerular endothelium stained strongly for UEA, 5'N, and Ia. Our results suggest that previous reports of the presence of IDC in renal tissue on the basis of staining for Ia on frozen tissue may be due to staining of compressed or obliquely sectioned vascular structures that were not adequately visualized.

Enzymes↗
PubMed1985

Comparison of fetal, newborn, and adult wound healing by histologic, enzyme-histochemical, and hydroxyproline determinations.

We compared simultaneous healing processes in fetal, newborn, and maternal rabbits using a miniaturized wound cylinder of expanded Gore-Tex tubing. The tubing was placed subcutaneously in fetal and maternal rabbits on day 23 of pregnancy (term = 31 to 32 days), and in 7-day-old newborn rabbits. At specific intervals, the tubing was removed and analyzed for hydroxyproline accumulation, histology, and cellular enzyme-histochemistry. Granulation tissue ingrowth and accumulation of hydroxyproline were each inversely related to age (fetus greater than newborn greater than maternal). The fetus showed an impressive infiltration of macrophages by day 4, fibroblasts by day 7, and a conspicuous lack of neutrophils in all specimens. Newborns and mothers had few cells until day 7, when a mixture of macrophages, neutrophils, and some fibroblasts appeared. We conclude that the fetus heals wounds rapidly by both mesenchymal cell proliferation and collagen deposition, and that these processes are more rapid in fetuses than in newborn or adult animals despite relative fetal hypoxemia.

Age Factors↗
PubMed1985

Enzyme histochemistry in plastic-embedded sections of normal and diseased kidneys.

Interest in the role of mononuclear phagocytes in glomerulonephritis (GN) and in defining markers of renal neoplasms led the authors to study alpha-naphthyl acetate/butyrate esterase (ANAE/ANBE), alkaline phosphatase (AlkP), acid phosphatase (AcP), 5'-nucleotidase (5'N), and ATPase (ATP) activity in paraformaldehyde-fixed, plastic-embedded renal tissue from patients with a variety of pathologic conditions. These conditions included GN, renal tumors, and transplant rejection. Enzymatic staining for ANAE, ANBE, AcP, AlkP, and ATP was generally confined to tubules and collecting ducts in normal kidney. Nine of 10 cases of renal carcinoma had weakly to strongly positive reactions with AlkP, AcP, and ANAE; 9 of 10 cases of Wilms' tumor showed weakly positive reactions with AcP and ANAE, particularly in tubular structures. Severely damaged kidney allografts showed surprising retention of normal histochemical features. In all cases 5'N stained both glomerular capillaries and interstitial vasculature; ATPase and AlkP stained interstitial vessels only. Plastic embedding provides superb preservation of both microscopic anatomy and enzymatic activity, which may allow utilization of enzyme histochemistry for diagnostic and research purposes.

5'-Nucleotidase↗
PubMed1985

Diffuse malignant lymphoma with cerebriform nuclei: A B-cell lymphoma studied with monoclonal antibodies.

A lymph node biopsy performed on a 55-year-old woman with asymptomatic generalized lymphadenopathy revealed a diffuse, malignant lymphoma composed of small to intermediate-sized lymphocytes with cerebriform-shaped nuclei; electron microscopy confirmed the nuclear complexity. The cerebriform nuclear configuration, coupled with an interfollicular pattern of nodal involvement with encroachment upon residual germinal centers, was presumptive of either mycosis fungoides or a peripheral T-cell lymphoma. Immunologic evaluation, however, indicated that the cerebriform lymphocytes represented a monoclonal B-cell population (IgM-IgD, lambda). Staining with monoclonal antibodies disclosed a phenotype of Ia+, B1+, BA-1+, BA-2+, Leu-1+; the neoplastic cells were unreactive with T-cell, lineage-specific antibodies (anti-Leu-2a, -3a, -4, -5) and with J5 (CALLA). In light of the immunophenotype and the distributional pattern, the cerebriform-shaped lymphocytes may represent an extreme morphologic variant of intermediate lymphocytic lymphoma.

Antibodies, Monoclonal↗