Search PubMed⌕ Search

Biomedical subjects

D Myerson

Publications and source records attributed to D Myerson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Diffuse intestinal ulceration after marrow transplantation: a clinicopathologic study of 13 patients.

The cases of 13 allogeneic marrow transplant recipients who had undergone laparotomy for manifestations of severe enteritis were reviewed to determine the causes of the severe intestinal disease and to assess the relation between clinical, histologic, and microbiologic findings. Laparotomies were performed a median of 63 days (range, 11 to 273 days) after transplantation for suspected peritonitis, intestinal obstruction, or bleeding. Intestinal tissue was available from small bowel resections in nine patients, intraoperative biopsies in one, and from autopsies in three patients who died shortly after laparotomy. Widespread small bowel ulceration was present in all 13 cases. Four causes of ulceration were identified: chemoradiation toxicity (n = 2), acute graft-versus-host disease (GVHD) (n = 5), opportunistic infections superimposed on either GVHD or toxicity from chemotherapy (n = 4), and Epstein-Barr virus-associated lymphoproliferative disorder (n = 2). Intestinal infections, unrecognized before laparotomy, were due to cytomegalovirus (CMV), herpes simplex virus (HSV), adenovirus, and Torulopsis glabrata. CMV- and HSV-infected cells, often lacking diagnostic inclusions, were identified in the intestine by in situ hybridization with biotinylated DNA probes. Eleven patients died in the perioperative period, and two died 452 and 558 days after surgery of complications of chronic GVHD. Poor outcomes were related to extensive intestinal involvement, which was commonly underestimated before surgery, failure to diagnose intestinal infections early, poor marrow function, impaired immunity, and refractoriness of severe GVHD.

Acute Disease↗
PubMed1986

Use of bronchoalveolar lavage to diagnose acute diffuse pneumonia in the immunocompromised host.

We compared the diagnostic information obtained by bronchoscopy and needle aspiration of the lung with information obtained concurrently by open-lung biopsy in 15 marrow transplant recipients. Bronchoscopy included a wash, brush, and bronchoalveolar lavage. Laboratory evaluation included standard histological and cytological methods, specific immunofluorescence with monoclonal antibodies, and DNA hybridization to detect cytomegalovirus (CMV). Bronchoscopy permitted diagnosis of five of six patients with CMV pneumonia, whereas needle aspiration alone permitted diagnosis of only one of six. Bronchoalveolar lavage alone provided the diagnosis in four of six patients. Bronchoscopy also identified the bacterial component of a combined infection and identified one case of primary lung hemorrhage. Immunofluorescent staining and hybridization studies each diagnosed one case of CMV pneumonia not identified by standard techniques. The diagnostic sensitivity of the bronchoscopy was 89%, as compared with 17% for needle aspiration, and there were no complications.

Antibodies, Monoclonal↗
PubMed1986

Viral diagnosis by in situ hybridization. Description of a rapid simplified colorimetric method.

An improved method of colorimetric in situ hybridization for the diagnosis of viral infections in standard formalin-fixed, paraffin-embedded tissue sections has been developed. This method employs a 2-hour hybridization with biotin-labeled DNA probes followed by direct colorimetric detection with avidin-alkaline phosphatase complexes. Visual results are obtained within 8 h of cutting the tissue section. Specific histologic localization of cytomegalovirus and adenovirus genetic information has been achieved in infected lung tissues from autopsy or biopsy. Simultaneous denaturation of tissue and probe DNA at elevated temperature (100-105 degrees C) resulted in increased signal. It is our suggestion that these denaturing conditions may be required to denature more fully formalin cross-linked tissue DNA and favor penetrance of probe into the tissues. Comparison of the results of hybridization and viral culture for the diagnosis of CMV infections suggest that in clinical situations hybridization will allow specific diagnosis of productive viral infection more rapidly than viral culture with some loss in sensitivity. Colorimetric in situ DNA hybridization offers the surgical pathologist a powerful new technique that provides an alternative to immunocytochemistry and electron microscopy in the diagnosis of viral pathogens.

Adenoviridae Infections↗
PubMed1986

Detection of viral DNA and RNA by in situ hybridization.

Using cloned restriction endonuclease fragments of Herpes simplex virus (HSV), human papillomavirus (HPV), and cytomegalovirus (CMV) DNA as probes, viral DNA and RNA sequences have been detected in human tissues. The probes were labeled either with a radioactive isotope, for subsequent detection by autoradiography, or with biotin. This latter technique has been successfully used to visualize HPV DNA in tissues that have been fixed in formalin and embedded in paraffin, and is therefore of value in retrospective studies of histological specimens. HPV DNA was detected under non-stringent conditions (Tm = -42 degrees C) with heterologous probes in plantar and common warts, laryngeal papillomas, and anogenital condylomas. The specific type of HPV was established using stringent hybridization conditions (Tm = - 17 degrees C). Results from these and from malignant tissues show the distribution and localization of HSV and HPV RNA and DNA sequences in malignancies of squamous cell origin in the anogenital region. Both HSV and HPV DNA sequences have occasionally been detected in the same tumor, providing a further impetus to test the hypothesis that an initiator-promoter relationship might involve these common human viruses in the development of some tumors.

Base Sequence↗
PubMed1986

A single-step silver enhancement method permitting rapid diagnosis of cytomegalovirus infection in formalin-fixed, paraffin-embedded tissue sections by in situ hybridization and immunoperoxidase detection.

A single-step silver enhancement method was developed which intensifies the polymerized nickel-complexed diaminobenzidine (Ni-DAB) reaction product of peroxidase. With such enhancement, an in situ hybridization procedure can be performed in less than 8 hr by using a 2-hr hybridization incubation and direct detection. Cytomegalovirus (CMV)-infected lung sections were hybridized in situ for 2 hr with a biotinylated CMV genomic-length probe. The probe was detected directly with avidin-biotinylated peroxidase using Ni-DAB as the substrate, and the reaction product was enhanced with silver. Silver was deposited only on the Ni-DAB and not on normally argyrophilic substances. Indirect detection of the probe using a sandwich technique before silver enhancement proved more sensitive, but the length of the procedure was increased without substantially changing the result (infection vs. no infection). Sensitivity was also improved by omitting the dehydration step before applying the probe, and by increasing the temperature and duration of denaturation. In a blinded study of 21 open-lung biopsies, 13 of 13 culture-negative specimens were negative by hybridization, and 7 of 8 culture-positive specimens were positive by hybridization. Modified short hybridization with a biotinylated probe and silver-enhanced direct detection therefore provides a rapid but sensitive method for diagnosis of viral infection.

3,3'-Diaminobenzidine↗
PubMed1985

Detection and localization of human papillomavirus DNA in human genital condylomas by in situ hybridization with biotinylated probes.

We have examined the distribution of human papillomavirus (HPV) DNA in paraffin sections of humans warts by in situ hybridization with biotin-labeled DNA probes. Recombinant plasmid DNAs (HPV-1, -6, -11, -16) were labeled by nick translation with biotinylated deoxyuridine triphosphate. Paraffin sections were hybridized with the probes for 18 h in stringent or non-stringent conditions, and DNA-DNA hybrids were detected by immunocytochemistry. Paraffin sections of warts were also examined for the presence of HPV capsid antigen with the avidin-biotin peroxidase complex method for immunocytochemistry. HPV DNA was detected and localized in paraffin sections from a plantar wart, a laryngeal papilloma, and seven anogenital condylomas. The specific HPV type present in each lesion was determined by hybridization under stringent conditions with the homologous DNA probe. The papillomas were found to contain many more cells with replicating virus DNA, as demonstrated by in situ hybridization, than was apparent from the number of cells containing detectable virus antigen. In situ hybridization with biotin-labeled probes is an effective technique for the identification of HPV infection in routinely collected and processed tissue specimens.

Antigens, Neoplasm↗
PubMed1985

Detection of species specific chromosomes in somatic cell hybrids.

We describe an in situ hybridization technique which allows rapid identification of species-specific chromosomes in somatic cell hybrid lines. Chromosome preparations from rodent-human hybrid lines are hybridized to biotinylated total human DNA which is subsequently detected by a series of immunocytochemical reactions which culminate in a peroxidase reaction visible by light microscopy. This technique not only allows identification of intact human chromosomes but also fragmented and rearranged human chromosomal segments. We have detected as little as 1 X 10(7) bp of human DNA inserted into a mouse chromosome using this procedure and estimate that the sensitivity of the technique would allow detection of sequences 5- to 10-fold smaller. The usefulness of the technique for screening hybrid cell gene mapping panels is discussed.

Animals↗
PubMed1985

Rapid diagnosis of cytomegaloviral pneumonia by tissue immunofluorescence with a murine monoclonal antibody.

A murine monoclonal antibody to cytomegalovirus (CMV) was used to identify virus-infected cells in coded frozen tissue sections from 52 consecutive open-lung biopsies obtained from marrow transplant recipients with pneumonia. The diagnostic sensitivity of immunofluorescence (IF) using this antibody exceeded that of standard histology performed on touch imprints and frozen and permanent lung sections and was equal to viral culture and in situ CMV nucleic acid hybridization. In comparison with patients with CMV pneumonia demonstrated histologically and by IF, those with negative histology and positive IF were more likely to have seroconverted before biopsy. Despite this evidence of an immune response to CMV pneumonia, the two groups did not differ in CMV positivity by culture or by hybridization, and their long-term survival was equally poor. The findings demonstrate that this antibody can play an important role in both the rapid diagnosis of CMV infection and the elucidation of CMV pathophysiology.

Antibodies, Monoclonal↗
PubMed1984

Widespread presence of histologically occult cytomegalovirus.

Disseminated cytomegalovirus (CMV) has been investigated by in situ hybridization in formalin-fixed paraffin-embedded tissue sections with biotinylated DNA probes. Two cases of disseminated CMV infection were studied at autopsy by this highly specific technique. The presence of CMV in cytomegalic cells is readily shown. In addition, CMV has been detected and localized in many normal-appearing cells. This occult infection occurs in cardiac myocytes, hepatocytes, spleen and lymph node reticular cells, endometrial stromal and glandular cells, and breast stromal cells, as well as in cells in the renal glomerulus, tubule, and interstitium, adrenal cortex and medulla, fallopian tube submucosa, myometrium, and anterior pituitary. Cytomegalovirus infection of endothelial cells has been further documented by immunohistochemical methods utilizing antibody to Factor VIII. These findings suggest that CMV disseminates hematogenously throughout the body, initiating necrotizing foci of infection. The appearance of many diffuse foci suggests that local viral spread occurs via endothelial cell infection. Surprisingly , lymphocyte involvement was not observed.

Adult↗
PubMed1984

Diagnosis of cytomegaloviral pneumonia by in situ hybridization.

Cytomegalovirus was assayed by in situ hybridization in 29 consecutive specimens obtained by open-lung biopsy. Biotin-labeled cytomegaloviral DNA was hybridized to formalin-fixed, paraffin-embedded tissue sections and was detected by an immunoperoxidase procedure. The sensitivity of this technique was similar to that of both viral culture and viral antigen detection in frozen sections by monoclonal antibody. Cytomegaloviral infection was diagnosed within 24 hr by study of the formalin-fixed, paraffin-embedded sections of lung tissue. The assay was specific, reproducible, and readily applicable both to the study of multiple tissue sections for diagnostic purposes and to retrospective studies. Hybridization studies of multiple sections from two patients with fatal cases of pneumonia showed that cytomegaloviral infection is not homogeneous in all cases.

Antibodies, Monoclonal↗
PubMed1984

HSV, CMV, and HPV in human neoplasia.

We are studying the role of sexually transmitted viruses in the development of human tumors. The persistence of herpes simplex virus, cytomegalovirus, and human papillomavirus nucleic acid sequences has been examined using cloned viral DNA sequences as probes. The relationship of the viruses to various stages in the progression of neoplasia is examined, with particular reference to the role of viral and/or cellular genes in the initiation, promotion, and maintenance of the neoplastic phenotype. The human tumors of major interest in this context are carcinomas of the cervix, vulva, and anus and Kaposi's sarcoma. The minimal fragment of HSV-2 DNA detected in cervical tumors is contained within a 656-bp sequence that can be used in transfection experiments to transform rodent cells in vitro to a malignant phenotype. However, neither this fragment nor any other is consistently retained in cervical tumors, suggesting that this viral DNA may initiate but not maintain the transformed phenotype.

Carcinoma↗
PubMed1983

Detection of viral genomes in cultured cells and paraffin-embedded tissue sections using biotin-labeled hybridization probes.

A method of in situ cytohybridization is described for the detection of specific viral genomes in infected cell cultures or paraffin-embedded tissue sections without the use of radioisotopes. Biotin-labeled analogs of TTP are incorporated into viral DNA in vitro by nick translation and the resultant DNA probes hybridized to cytologic samples. Cells containing viral genetic material are then revealed by standard immunofluorescence, immunoperoxidase, or affinity cytochemical techniques that are based on the specific interaction between biotin and antibiotin IgG or avidin. Hybridization probes containing nucleotides that have an 11- or 16-atom spacer arm between the biotin molecule and the pyrimidine ring interact with these detector proteins more efficiently than probes containing biotin-nucleotides with a 4-atom spacer arm. The total procedure can be performed fairly rapidly (24 hr or less) and numerous samples can be processed simultaneously. Although the detection methods employed to date are not as sensitive as autoradiographic procedures with high specific activity probes, more sensitive protein detector complexes are currently being constructed. The speed, specificity, and resolving power of this technique should be of general utility in screening for the presence of infectious agents in cell or tissue samples. Here we report the visualization of parvovirus, polyomavirus, herpes simplex virus, adenovirus, and retrovirus genetic material in infected cell cultures and herpes simplex and adenovirus DNA in paraffin-embedded autopsy tissues.

Adenoviruses, Human↗
PubMed1983

Prophylactic and therapeutic treatment with acyclovir of genital herpes in the guinea pig.

The antiviral drug, acyclovir, was tested on experimentally infected guinea pigs with either of two herpes simplex virus type 1 (HSV-1) isolates following intravaginal inoculation. The drug was continuously infused subcutaneously utilizing an osmotic pump. Infusion was begun either prior to virus inoculation (prophylactic) or after virus inoculation at the time of first appearance of lesions (therapeutic). Prophylactic treatment markedly reduced the severity of the genital lesions, the appearance of acute neurologic sequellae, and the virus excretion in the genital tract of guinea pigs infected with either of the two strains tested. Therapeutic acyclovir treatment, however, did not decrease the incidence of acute neurologic sequellae with one of the two HSV-1 strains tested, nor did it reduce the severity of the genital lesions of either strain. These neurologic sequellae may be due to insufficient levels of ACV in the central nervous system as the concentration of ACV in the dorsal root ganglia was found to exceed that of the plasma, but only trace amounts of acyclovir were present in the brain and spinal cord. Continuous perfusion of ACV gave far higher tissue levels than intermittent injections. These findings suggest that prophylactic ACV is far more effective than therapeutic treatment for genital herpes in the guinea pig model.

Acyclovir↗
PubMed1980

Gastroduodenitis. A broader concept of peptic ulcer disease.

To evaluate the frequency and type of gastroduodenal mucosal inflammatory changes in patients with symptomatic acid peptic disease and nonulcer dyspepsia, 100 patients with gastrointestinal symptoms indicative of acid peptic disease or dyspepsia and 10 control subjects were clinically evaluated and underwent radiographic, endoscopic, and biopsy studies of the stomach and duodenum. Clinical evaluation revealed that of the 100 patients, 61% had classic and 39% had atypical manifestations of acid peptic (ulcer) disease. Endoscopic and histologic evaluation revealed that 25 patients had peptic ulcer craters, 86-90% of whom had associated gastroduodenitis. Thirty-nine patients had acute and 20 patients had chronic gastroduodenitis without ulcer crater. Twelve symptomatic patients had no histologic changes in the gastroduodenal mucosa. Two of the ten control subjects had mild gastritis. In the 61% of the patients with classic manifestations of peptic ulcer disease, we could not clinically distinguish the 24 patients with craters, (40% of the classic group) from the 25 patients with acute gastroduodenitis without craters (41% of the classic group). As a result of this study of our group of patients, we believe that gastroduodenitis can be symptomatic and may present with the same manifestations as peptic ulcer crater. Further study will be required to determine whether gastroduodenitis is an independent entity or part of the spectrum of acid peptic (ulcer) disease.

Adult↗
PubMed1979

Renal capsular tumors: the angiographic features.

Five masses of the renal capsule, which were studied angiographically, demonstrated a typical inward displacement of the renal parenchyma, and prominence and variable displacement of the renal capsular arteries. Benign lesions typically lacked malignant neovascularity and had a sharp interface with the renal parenchyma. The angiographic characterization of renal capsular lesions may help in identification of benign lesions and prevent unnecessary nephrectomy.

Abscess↗