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Biomedical subjects

H Popper

Publications and source records attributed to H Popper.

At least 19 recordsLinked to original sources

Primitive neuroectodermal tumor arising in the skin. Differentiation from neuroendocrine carcinoma of the skin.

We report a 25-year-old male patient with primitive neuroectodermal tumor presenting as a subcutaneous tumor on the right buttock, which was initially diagnosed as neuroendocrine carcinoma of the skin. Subsequently, local recurrence and metastatic spread to the lung occurred. The tumor was resistant to highly aggressive chemotherapy. The patient died 6 months later with severe pulmonary and lymph node involvement.

Adult

Total unilateral lung gangrene in Hodgkin's disease: treatment by thoracostomy.

Total gangrene of the left lung developed in a 30-year-old male patient with a pulmonary recurrence of Hodgkin's disease after mediastinal irradiation and chemotherapy. Clinically, tension pyopneumothorax and severe septic shock were present. Surgical repair was done by thoracostomy, resecting three ribs. A 2 x 0.5-cm hole in the necrotic wall of the left main bronchus was covered with an intercostal muscle bundle. The necrotic pleural surfaces were treated openly by daily change of dressings. The patient recovered satisfactorily and underwent four further courses of chemotherapy without any complications.

Adult

The significance of infections with two types of viral hepatitis demonstrated by histologic features in chimpanzees.

In view of the recognized importance of necroinflammatory episodes in chronic hepatitis B virus (HBV) infection, chimpanzees, either HBV surface antigen (HBsAg) carriers or noninfected (naive), were infected with other primary hepatotropic viruses to evaluate histologic alterations and changes in virologic and biochemical markers of infection. The advantages of studies on chimpanzees are the availability of serial biopsy specimens and the viral type-specific histologic lesions, not as well recognized in humans. Infection with hepatitis A and non-A, non-B (NANB) agents produced more severe lesions in chronic HBsAg carrier chimpanzees than in naive animals. During this superinfection, the specific expression of the second agent was predominant, indicating that the exacerbation is caused by the second agent, but that carriers are prone to more severe disease than the naive chimpanzees. Hepatitis delta virus (HDV) infections were always coexistant with HBV and superinfection of carriers produced histologic changes more severe than those seen in any other type of viral hepatitis. Such HDV infections revealed less evidence of lymphocytotoxicity but rather of cytotoxicity, and sometimes resembled in appearance the histopathology of NANB. Coinfection of HDV and HBV and superinfection of HBV-carriers with NANB resulted in hepatitis that was far less severe than superinfection of HDV in HBV carriers, greatly in keeping with human experiences. HBV replication was suppressed transiently in both NANB and HDV superinfection. This implies that in exacerbations during chronic HBV infections of humans, suppression of HBV replication markers indicates superinfection, for instance, by NANB for which markers are so far not widely available; by contrast, elevated markers of HBV replication suggest reactivation of the original HBV infection.

Animals

Pitfalls in intraoperative frozen section histology of mediastinal neoplasms.

We evaluated the reliability of intraoperative frozen section histology in 149 mediastinal tumours of which 106 lesions were localized in the anterior, 18 in the central and 25 in the posterior mediastinum. Gross non-resectability was ruled out by preoperative imaging. No preoperative cytological or histological diagnosis was obtained in any case. At thoracotomy, 3 biopsies from 3 different sites of the tumour were processed for frozen section as well as for paraffin histology and immunohistochemistry. In 67 of 73 benign lesions (91%), the intraoperative diagnosis was correct, 5 cases could not be classified by frozen section and 1 case had to be revised. Only 28 of 76 malignant lesions (36.8%) were diagnosed correctly by intraoperative frozen section. In 27 cases (35.5%), no intraoperative classification was possible and in 21 patients (27.6%), the diagnosis was wrong with the consequence of surgical overtreatment for lymphoma misinterpreted as thymic cancer in 3 cases. In patients in whom preoperative investigations suggest borderline resectability, a staged procedure to obtain histology prior to definitive surgery could prevent overtreatment.

Adolescent

Intraoperative radiation with external irradiation: an alternative for nonresectable non-small-cell lung cancer?

In 15 patients with nonresectable non-small-cell lung carcinoma (NSCLC) (10 squamous, 1 large cell, 4 adenocarcinomas; T1-T3, N0-N2, all M0), lymph node dissection and intraoperative irradiation of the tumour (IORT) with doses between 10 and 20 Gy (11-20 MeV electron beam) was performed. Four weeks postoperatively 46-56 Gy external irradiation (8 or 23 MeV photons) was delivered to the mediastinum and 46 Gy to the tumour-bearing area. Four weeks postoperatively, 8 minor responses (MR, tumour regression between 4% and 45%) and 6 partial responses (PR, 50%-84%) were found. In 1 case, CT was inconclusive. Eighteen weeks after IORT, volumetry showed 3 CR, 9 PR (62% to 94%) and 1 28% MR. One patient died from intrabronchial hemorrhage 7 weeks after IORT (50% PR). Two others (both CR) died from unrelated causes, 6 and 12 months, respectively, after IORT. One patient (62% PR) died after 14 months from an unknown cause. Another patient died at 15 months from local relapse after CR. The latest CT volume assessment between 7.5 and 21.5 months, respectively, yielded 8 CR, and 1 63% PR. One further case of local CR has developed contralateral pulmonary metastasis after 10 months. All these patients are alive and well. The median time elapsed since IORT is 12.5 months, 10 patients have survived more than 12 months.

Aged

Quantitative evaluation of melanoma cell invasion in three-dimensional confrontation cultures in vitro using automated image analysis.

Tumor invasion is a crucial feature of tumor growth in vivo. Confrontation cultures of multicellular melanoma spheroids and embryonic chick heart fragments provide a model for invasive growth in vitro. We have developed an image analysis method, which facilitates the objective measurement of tumor cell invasion in this model. Cryostat sections of confrontation cultures were immunohistochemically stained with an antiserum directed against the stromal component for automated recognition of the stroma tissue. The slides were automatically processed by a grey level based computerized image analysis system. On Spearman's rank correlation test, 25 out of 39 parameters correlated with the reference value of invasion, which was derived from the subjective evaluation of five independent observers. Two parameters combining the stroma margin and the total amount of stroma tissue completely reproduced the judgement of the morphologists in our test set. The quantitative evaluation of tumor invasion in vitro by automated image analysis may be helpful in pharmacologic and pathogenetic studies of tumor growth.

Animals

Composition of fat in different types of liposarcomas in comparison with lipomas.

Different types of liposarcomas, and for comparison, lipomas were investigated for their lipid composition. Triglycerides were the main components of lipomas and lipoma-like liposarcomas. Myxoid liposarcomas had a high water content and contained considerable amounts of free cholesterol and phospholipids. One pleomorphic liposarcoma resembled a myxoid liposarcoma in its lipid composition and water content. In 4 liposarcomas of mixed type the lipid composition resembled the main subtype. A glycerol ether-like fraction was found in all lipoma-like (well differentiated) liposarcomas, in one myxoid type but not in the other types.

Chemical Fractionation

Hepatocellular carcinoma in woodchuck hepatitis virus-infected woodchucks: presence of viral DNA in tumor tissue from chronic carriers and animals serologically recovered from acute infections.

During long-term studies of the natural history of woodchuck hepatitis virus infection, five cases of histologically confirmed, primary hepatocellular carcinoma were observed in a total of 92 woodchucks which had recovered, by analysis of viral serologic markers (WHsAg-, anti-WHc+, anti-WHs+), from experimental acute woodchuck hepatitis virus infections 20 to 30 months prior to the detection of hepatocellular carcinoma. No hepatocellular carcinoma was observed in 167 uninfected controls at least 3 years of age and held in the same laboratory environment. Southern blot hybridization analysis of liver tissue taken from four of these recovered woodchucks revealed the presence of low levels (0.1 to 0.3 copies per cell) of integrated woodchuck hepatitis virus DNA in hepatocellular carcinoma (four of four animals) and nonneoplastic tissue (three of four animals). Similarly, hepatocellular carcinoma tissue obtained from two wild-caught, naturally infected and serologically recovered woodchucks also contained low levels of integrated woodchuck hepatitis virus DNA. Liver tissues from another 27 of these 92 recovered woodchucks (without hepatocellular carcinoma) were examined for woodchuck hepatitis virus nucleic acids 13 to 31 months following experimental woodchuck hepatitis virus infection. Nonreplicating woodchuck hepatitis virus DNA was present in the liver of eight (30%) and in the peripheral blood lymphocytes from eight (30%) of these 27 animals. These results were in marked contrast to the analysis of woodchuck hepatitis virus DNA in the liver tissue of chronic woodchuck hepatitis virus carriers (20 experimentally infected and nine naturally infected). In these animals, high levels of replicating woodchuck hepatitis virus DNA (up to 2,000 copies per cell) were observed in all hepatocellular carcinoma and nonneoplastic liver tissue. Integrated woodchuck hepatitis virus DNA was found in eight of 60 individual hepatocellular carcinomas detected in 29 chronic carriers, 15 to 40 months postinfection. Integrated woodchuck hepatitis virus DNA was present in the nonneoplastic tissue from four of these 29 chronic woodchuck hepatitis virus carriers.

Animals

Activation and release of enzymes and major basic protein from guinea pig eosinophil granulocytes induced by different inflammatory stimuli and other substances. A histochemical, biochemical, and electron microscopic study.

In order to investigate the availability and release of enzymes from eosinophilic granulocytes in response to a variety of stimuli, guinea pig peritoneal eosinophils were obtained after repeated intraperitoneal injections of freeze-dried Trichinella spiralis larvae. The activities of the enzymes peroxidase, arylsulfatase B, beta-glucuronidase, aminopeptidase, histaminase, cytochrome c oxidase, acid phosphatase, adenosine triphosphatase and glucose 6-phosphatase, and the major basic protein (MBP) were studied histochemically and, in part, also biochemically. Eosinophils were incubated with the following substances: histamine, platelet activating factor, calcium ionophore, compound 48/80, leukotriene B4, prostaglandins E1, and E2, heparin, and eosinophil-chemotactic factors from neutrophils and lymphocytes. Eosinophils displayed a selective and stimulus-dependent enzyme and MBP reaction. Calcium ionophore and compound 48/80 provoked a release of cytotoxic major basic protein, partly associated with peroxidase release, while leukotriene B4 and eosinophil chemotactic factors caused histaminase and peroxidase release and activated leucinaminopeptidase. Heparin and calcium ionophore induced release of both MBP and histaminase. These data support the concept that eosinophils exhibit either inflammatory or cytotoxic, or antiinflammatory properties upon stimulation by various agents.

Animals

Natural history of woodchuck hepatitis virus infections during the course of experimental viral infection: molecular virologic features of the liver and lymphoid tissues.

In this study, the kinetic patterns of woodchuck hepatitis virus (WHV) infection were monitored in the liver and the five primary components of the lymphoid system (peripheral blood lymphocytes, lymph nodes, bone marrow, spleen, and thymus). Groups of woodchucks experimentally infected with a standardized inoculum of WHV were sacrificed at different times over a 65-week period beginning in the preacute phase of viral infection and continuing to the period of serologic recovery or the establishment of chronic infections and subsequent hepatocellular carcinoma. Infection by WHV was not limited to the liver but involved the major components of the lymphoid system during all stages of virus infection. A complex series of kinetic patterns was observed for the appearance of WHV DNA in the different lymphoid compartments and the liver during the entire course of viral infection. A progressive evolution of different WHV genomic forms related to the replicative state of WHV was also observed. Lymphoid cells of the bone marrow were the first cells in which WHV DNA was detected, followed in order by the liver, the spleen, peripheral blood lymphocytes, lymph nodes, and finally the thymus. Several differences were observed in the cellular WHV DNA patterns between woodchucks that developed chronic WHV infections and those that serologically recovered from acute WHV infections. The observations compiled in this study indicate that the host lymphoid system is intimately involved in the natural history of hepadnavirus infections from the earliest stages of virus entry.

Animals

Rheumatoid arthritis with extensive lung lesions.

A man of 74 who had had seropositive rheumatoid arthritis for 10 years presented with dyspnoea and reticular striation in both lung fields. At necropsy two years later there was pulmonary fibrosis with multiple rheumatoid nodules and non-specific granulomas.

Aged

Histologic features in autoimmune hepatitis.

In order to see if the term of "plasma cell hepatitis", dating back to the early sixties, is still valid as a morphological diagnosis for autoimmune chronic hepatitis (AICH), and to find out if the existence of several subgroups is reflected by histopathology, we investigated 26 patients with chronic hepatitis, who met the criteria of autoimmune hepatitis based on tests for antinuclear, anti-smooth muscle antibodies (SMA) and on immunoassays for liver-kidney-microsomal (LKM) antigen, liver membrane antigen (LMA), and soluble liver antigen (SLA). In our material autoimmune hepatitis represent the entire spectrum of chronic hepatitis with variable inflammatory activity ranging from chronic persistent hepatitis to severe inflammatory lesions in chronic active hepatitis with transition to cirrhosis. When compared to viral chronic hepatitis A and non-A, non-B, however, characteristic features can be evaluated consisting in broad hypocellular areas of collapse and microacinar transformation of hepatocytes with hydropic swelling being the predominant type of cell lesion. Eosinophilic clumping and acidophilic necrosis were insignificant. Plasma cells were not a constituent feature of AICH. From this histopathologic pattern it may be concluded that the disease seems to run a sluggish course in most patients, however, in few cases a dramatic development may determine the disease with fatal acute episodes which are terminated by death or fade into slow progression. The different subgroups could not be distinguished by histopathology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The goal. 1967.

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Education, Medical

Aetiological association of a virus-like particle with enterically transmitted non-A, non-B hepatitis.

Virus-like particles, approximately 27 nm in diameter, were identified in faeces from an Indian patient with enterically transmitted non-A, non-B (ENANB) hepatitis. They were serologically distinct from hepatitis A virus (HAV). Nucleic acid extracted from the particles did not hybridize with cDNA probes representing the genomes of HAV, enteroviruses, and cardioviruses. Chimpanzees were experimentally inoculated with faecal suspensions containing this 27 nm particle or with faeces from another case of ENANB hepatitis. Mild histological and biochemical hepatitis developed in these animals and there was serological evidence of infection with the virus-like particle as shown by immunoelectronmicroscopy (IEM). Serological analysis by IEM suggested that this agent or an antigenically similar virus was the aetiological agent of two epidemics and a sporadic case of ENANB hepatitis in India and of an epidemic of the illness in the USSR. Antibody to the particle was found in sera from patients with ENANB hepatitis from various geographic areas over a 30-year period.

Animals

Viral versus chemical hepatocarcinogenesis.

Almost all experimental studies on hepatocarcinogenesis have been performed on models induced by chemicals. The human hepatocellular carcinoma (HCC), a highly malignant tumor, particularly frequent in the Far East and in Africa, is overwhelmingly associated with hepatitis B virus (HBV) infections and only very rarely is it caused by chemicals. This raises the question as to what degree observations on the preferentially studied chemical carcinogenesis apply to human HCC. This question is timely, since a woodchuck model has been developed in which laboratory infection with a hepadna virus, biologically and genomically similar to HBV, regularly produces HCC in prolonged surface antigen carrier woodchucks. Permanent surface antigen carriage by itself may also be a risk factor. A comparison, based on available observations of chemical and hepadna viral carcinogenesis, was attempted on four aspects: (1) histologic features, (2) growth patterns, (3) growth factors, and (4) molecular biological observations. At this time, only few conclusions can be drawn, mainly on a morphological and molecular biological basis. In the initial stage, chemicals cause mutations of very few bases, while in hepadna viral infections long sequences are inserted into both strands of chromosomal DNA. Additional studies appear to be indicated, to the greatest degree with existing methods and primarily on hepadna viral carcinogenesis. A key question is whether the active necroinflammation, preceding or observed at the time the HCC is recognized, in woodchuck and also in human chronic HBV infections is a promoting event or a secondary reaction. Additional therapeutic strategies, specific for hepadna viral carcinogenesis, can be considered, particularly elimination of hepatocytes carrying integrated viral sequences and prevention or suppression of the promoting necroinflammation. Success in HCC may be applicable to cancers related to papilloma virus in other organs, for instance, the female genital tract.

Aflatoxins

Studies of prototype live hepatitis A virus vaccines in primate models.

We have prepared two prototype live hepatitis A virus (HAV) vaccines by serial passage of the HM-175 strain of HAV in African green monkey kidney cells. Passage 21 (P-21) HM-175 virus shows evidence of attenuation for chimpanzees but not for marmosets; passage 32 (P-32) HM-175 virus shows evidence of attenuation for both species. Animals that received P-32 HAV had fewer elevations in levels of liver enzyme activity and evidence of less virus replication in the liver and excretion of virus in stool than did those that received wild-type virus. The P-21 and P-32 viruses were highly immunogenic in both species. The information provided by this study will aid in the development of a live HAV vaccine.

Alanine Transaminase