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B Yoffe

Publications and source records attributed to B Yoffe.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Incarcerated diaphragmatic hernia presenting as colonic obstruction].

Diaphragmatic hernias in adults that are not categorized as hiatal hernias are rare. Hernias of the diaphragm itself appear in the perinatal age group and are defined as congenital hernias, presenting with severe respiratory distress and requiring immediate repair. There are a few asymptomatic post-partum cases in young children or adults. We present 3 cases of diaphragmatic hernia in men, aged 19, 20 and 74, respectively. 2 were admitted because of colonic incarceration with strangulation in the hernial sac. In the other case there was an incidental finding of incarcerated colon in a diaphragmatic hernia discovered in a patient who initially presented with unrelated thoraco-abdominal trauma. Contrary to the dominant clinical presentation as infant-respiratory distress, the predominant findings in adults are gastrointestinal complications. We believe successful treatment is more likely when there is a high level of awareness of the possibility of this kind of hernia in the adult, which can be a recurrence after perinatal hernia repair. It is essential to recognize that this is a combined thoraco-abdominal problem since it is often necessary to perform simultaneous laparotomy, thoracotomy and stoma formation.

Adult↗
PubMed1996

Effect of hepatocyte proliferation and cellular DNA synthesis on hepatitis B virus replication.

BACKGROUND & AIMS: Interrelationship between hepatitis B virus (HBV) replication and the stage of hepatocyte proliferation and differentiation may play an important role in the pathogenesis of HBV infection. The aim of this study was to assess the effect of hepatocyte proliferation and/or cell arrest on HBV replication. METHODS: Hepatoblastoma cells transfected with HBV were subjected to serum deprivation or treatment with aphidicolin or camptothecin. Cell cycle analysis was performed using flow cytometry, and cellular DNA synthesis was analysed by assessing 5-bromo-2'-deoxyuridine incorporation. Distribution of episomal HBV DNA and proliferating cell nuclear antigen in liver specimens was assessed by simultaneous in situ hybridization and immunohistochemistry. RESULTS: Serum deprivation inhibited cellular DNA synthesis and increased levels of HBV messenger RNA (mRNA). Aphidicolin treatment resulted in cell arrest in C1, with concomitant increases in levels of HBV mRNA and viral DNA. Cell entry into S phase inhibited expression of HBV mRNA. Camptothecin induced G2 cell arrest and inhibited cellular DNA synthesis with increased amounts of viral replication and levels of HBV mRNA. In vivo studies showed an inverse correlation between expression of proliferating cell nuclear antigen and presence of episomal HBV DNA in individual hepatocytes. CONCLUSIONS: HBV replication is cell cycle dependent, supporting the concept of enhanced viral replication in quiescent hepatocytes. The results may explain the mechanism of viral elimination during cell regeneration.

Cell Cycle↗
PubMed1996

Detection of Helicobacter pylori in paraffin-embedded gastric biopsy specimens by in situ hybridization.

Helicobacter pylori is the causative agent of chronic gastritis, peptic ulcers, and is also associated with gastric cancer. Eradication of H pylori infection has proven to be difficult to confirm. The authors developed a nonradioactive in situ hybridization method for detection of H pylori and compared it with conventional methods for diagnosis of the infection. Reverse transcription followed by polymerase chain reaction (PCR) with two 22-base primers was used to amplify a 520 base pair (bp) segment of 16S rRNA from H pylori. The PCR product was labeled with digoxigenin and used as a probe. Specificity of the probe was tested by dot blot hybridization against DNA from 30 different strains of related and unrelated bacteria. Specificity of in situ hybridization assay was proven by the lack of hybridization on sections with gram negative and positive bacteria other than H pylori, with an unrelated probe, without probe, and after RNase treatment. A random sample of 15 biopsy specimens was blindly studied by in situ hybridization method and the results were compared with those of culture and conventional histology. Comparison of in situ hybridization and conventional histology showed agreement in all 15 specimens (5 negative and 10 positive). Between culture and in situ hybridization there was agreement in 13 cases (8 positive, 5 negative). Two cases were negative by culture but positive by in situ hybridization and histology. Nonradioactive in situ hybridization provides a sensitive and specific method for detection of H pylori infection. It should be particularly useful for confirmation of infection in cases equivocal with other methods, and potentially useful in post-treatment evaluation.

Base Sequence↗
PubMed1996

p53 abnormalities in hepatocellular carcinoma from United States patients: analysis of all 11 exons.

Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely. p53 Exons 1 to 11 were analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing in HCCs from 12 patients from the United States and in adjacent non-tumorous liver from 10 of them. Abnormalities of the p53 gene were found in five of the 12 tumors, including mutations in exon 4 (one patient), exon 5 (one patient) and exon 8 (three patients). In all 12 tumors, a normal conformation of exon 7 was found; in five of these HCCs the absence of mutations was confirmed by direct sequencing. Thus, the mutations of p53 codon 249 that have frequently been found in HCCs from endemic areas apparently do not play a role in most HCCs in the United States. Since the mutations in codon 249 are thought to be due to aflatoxin ingestion, the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA.

Adolescent↗
PubMed1996

Diagnosing and treating cytomegalovirus pneumonia in patients with AIDS.

Because cytomegalovirus (CMV) can be isolated from pulmonary secretions of human immunodeficiency virus (HIV)-infected patients without causing disease, its clinical significance as a cause of pneumonia in this patient population is frequently questioned. In a 22-month period, CMV pneumonia was diagnosed in 17 (8%) of 210 HIV-infected patients who underwent lung biopsy on the basis of microbiological and histologic criteria. The clinical presentations of these patients were nonspecific, including fever (100% of patients), shortness of breath (71%), cough (76%), and Pao2 of < 75 mm Hg (88%). A high correlation in the degree of viral burden in lung biopsy specimens was demonstrated by histologic examination, immunohistochemical analysis, and in situ hybridization. No other pulmonary pathogens were identified for nine patients, whereas other possible causes of pneumonia were present in eight: 11 patients had evidence of extrapulmonary CMV disease at presentation. Most patients initially responded to specific anti-CMV therapy; the overall mean survival +/- SD was 3.1 +/- 2.5 months. CMV should be considered as a possible cause of pneumonia in patients with advanced AIDS especially if CMV infection is documented at other sites.

AIDS-Related Opportunistic Infections↗
PubMed1996

Ganciclovir treatment of active hepatitis B virus infection in a heart transplant patient.

Hepatitis B virus (HBV) infection in patients who undergo organ transplantation is a serious illness, associated with progressive and often fatal liver disease. Attempts at eradication of infection with antiviral agents, such as interferon and adenine arabinoside, have produced disappointing results. Similarly, prevention of HBV reinfection with the use of passive immunization with hepatitis B immunoglobulin or a combination of active and passive immunization have not been uniformly successful. We report the successful use of ganciclovir, a synthetic analogue of 2-deoxyguanosine, in a heart transplant patient with active HBV infection. The patient developed decompensated liver disease with ascites, edema, and marked derangement of liver tests despite drastic reduction in immunosuppressive therapy. Ganciclovir therapy was administered intravenously, and the patient showed remarkable improvement with clinical recovery and normalization of the liver tests. Moreover, the serum HBV DNA and hepatitis B e antigen became undetectable. Ganciclovir was a safe and effective treatment of HBV infection in this transplant patient.

Aged↗
PubMed1995

Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin.

BACKGROUND: Recent studies have demonstrated that the plant-derived alkaloid camptothecin (CPT) and its derivative, 9-nitro-CPT (9NC), are cytotoxic in tumorigenic cells but cytostatic in nontumorigenic cells in vitro and in vivo. Also, CPT induces differentiation of human leukemia cells in vitro along specific lineages. In this study, we have investigated the effects of 9NC on nontumorigenic HepG2 cells derived from human hepatoblastoma. A newly discovered senescent cell-derived inhibitor (SDI1) plays a critical role in the cell cycle, so we evaluated the effect of 9NC on the expression of the SDI1 gene. EXPERIMENTAL DESIGN: The effects of 9NC on HepG2 cells were evaluated by monitoring DNA synthesis, morphologic and ultrastructural changes of cells, and perturbation in the cell cycle and by assessing the levels of p53 protein and SDI1 mRNA. RESULTS: Treatment of HepG2 cells with 9NC results in a dose-dependent inhibition of cell proliferation and DNA synthesis. Flow cytometric analysis of DNA content showed that 9NC-treated HepG2 cells are arrested in the G2-phase of the cell cycle. Light and electron microscopic examination revealed that 9NC at low concentrations induces morphologic and growth features that resemble properties highly differentiated or senescent cells, i.e., increased cell size and decreased nuclear/cytoplasmic ratio, as well as enlarged numbers of lysosomes, mitochondria, and lipid in the cytoplasm. No significant alteration in the p53 protein level was noted in 9NC-treated cells. In contrast to untreated, logarithmically grown HepG2 cells, 9NC-treated cells arrested at the G2-phase of the cell cycle and contained increased levels of SDI1 mRNA. Kinetic studies revealed gradual increases in SDI1 mRNA synthesis. CONCLUSIONS: Induction of SDI1 mRNA by 9NC represents the first documentation that the SDI1 gene can be overexpressed in the G2-phase of the cell cycle and provides a valuable cell culture system to dissect the events controlling the G2 checkpoint. In addition, this finding corroborates the hypothesis that genes up-regulated in senescent cells can also be induced in tumor-derived immortalized cells.

Antineoplastic Agents↗
PubMed1994

Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation.

Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.

Adolescent↗
PubMed1994

Hepatic arterial infusion of floxuridine, leucovorin, doxorubicin, and cisplatin for hepatocellular carcinoma: effects of hepatitis B and C viral infection on drug toxicity and patient survival.

PURPOSE: To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival. PATIENTS AND METHODS: Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks. RESULTS: Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all). CONCLUSION: HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.

Aged↗
PubMed1993

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.

BACKGROUND: A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. METHODS: Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. RESULTS: Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. CONCLUSIONS: The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Adolescent↗
PubMed1993

In situ hybridization and immunohistochemical analysis of cytomegalovirus-associated ileal perforation.

A patient with the acquired immunodeficiency syndrome (AIDS) with a cytomegalovirus (CMV) infection localized in the area of an ileal Kaposi sarcoma resulting in perforation is described. Because only one case of such an association of Kaposi sarcoma with CMV leading to perforation has been reported, the presence and distribution of CMV-related nucleic acids and proteins in the affected segment of intestine were evaluated. By using in situ hybridization and immunocytochemical analyses the presence of CMV was shown within epithelial, endothelial, smooth muscle, and inflammatory cells at the site of perforation. This study not only confirmed that CMV can be detected in virtually all components of the intestinal wall despite the absence of distinctive cytomegalic changes, but also generated critical information that illustrates the usefulness of immunohistochemistry and in situ hybridization in elucidating the pathogenesis of CMV-associated lesions. These findings lend further support to the concept that CMV plays a pivotal role in the pathogenesis of intestinal perforation and emphasize the critical importance of in situ hybridization in gaining insight into the mechanisms of CMV-induced injury.

Antigens, Viral↗
PubMed1993

Myxomatosic aneurysm of a brachial artery in a child.

We present a case of an aneurysm in a brachial artery of a 4.5-year-old child which was resected with the interposition of a venous graft. Histological examination of the aneurysm showed a myxomatous damage to the wall of the vessel. Examination of the cardiovascular system did not reveal a myxoma of the heart. The available literature was searched for a similar description of an isolated aneurysm of a peripheral artery but none was found.

Aneurysm↗
PubMed1993

Southern-blot analysis and simultaneous in situ detection of hepatitis B virus-associated DNA and antigens in patients with end-stage liver disease.

To gain new insights into the pathogenesis of hepatitis B virus-induced chronic liver disease, we have used nonisotopic in situ detection methods for the simultaneous analysis of hepatitis B virus DNA and antigens at the single-cell level. Paraffin-embedded liver specimens from 23 cirrhotic patients (12 HBsAg positive and 11 HBsAg negative) who underwent liver transplantation were evaluated by in situ hybridization with a digoxigenin-labeled DNA probe and digoxigenin detection system and by immunohistochemistry with an enhanced biotin-streptavidin technique. DNAs extracted from liver and serum specimens were analyzed by Southern- and slot-blot hybridization, respectively. Using the in situ techniques, we detected hepatitis B virus-specific DNA and antigens in 11 of 12 HBsAg-positive patients and in none of the 11 HBsAg-negative individuals. Replicative intermediates of hepatitis B virus DNA were detected by Southern-blot analysis in the same 11 HBsAg-positive patients, 6 of whom had no serological markers of hepatitis B virus replication. Therefore a good correlation was found between the results obtained by the in situ and Southern-blot hybridization analyses of tissue specimens. However, a lack of correlation was found between serum- and tissue-associated markers of viral replication. In addition, the simultaneous in situ detection analyses revealed that some hepatocytes containing high levels of viral DNA were devoid of detectable HBcAg, suggesting a mechanism by which the virus may escape immunological surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1992

Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance.

In this study, peripheral-blood mononuclear cells from patients with chronic hepatitis B and spontaneous or therapy-induced disappearance of HBsAg were examined for HBV DNA. Samples were evaluated by in situ hybridization and polymerase chain reaction both before and after clearance of HBsAg. By in situ hybridization, positive signals were observed in 2 of 13 samples collected after HBsAg loss, in 8 of 15 samples before HBsAg loss and in 0 of 4 control patients without serological markers of active or prior HBV infection. When polymerase chain reaction analyses were performed, HBV DNA was detected in 5 of 12 HBsAg-negative samples and 10 of 15 HBsAg-positive samples from the study group. Testing of mononuclear cells after disappearance of HBsAg revealed that two of eight patients were HBV DNA positive by in situ hybridization and by polymerase chain reaction, whereas two additional patients were positive by polymerase chain reaction alone. Mononuclear cell-associated HBV DNA was detected between 2 and 9 mo after the disappearance of circulating HBsAg by in situ hybridization and as long as 4 yr later by polymerase chain reaction. These data indicate that patients who have undergone HBsAg seroconversion may nonetheless harbor HBV DNA in their peripheral-blood mononuclear cells for prolonged periods.

Adult↗
PubMed1992

Hepatitis B virus. New and evolving issues.

Recent developments in molecular biology have advanced our understanding of the pathogenesis of HBV-induced disease. New data derived from the molecular analysis of clinical material have begun to bridge the gap between bench research and the clinical arena. In this review, we consider topics that have relevance to clinical management and that have not been summarized in the recent literature. The recent advances that have been made in the areas of HBV variants, in vitro cell culture systems, and extrahepatic infection are discussed in greater detail.

Animals↗
PubMed1992

Simultaneous detection of HBV-specific antigens and DNA in paraffin-embedded liver tissue by immunohistochemistry and in situ hybridization using a digoxigenin-labeled probe.

To understand the pathogenesis of HBV infection at the single cell level, we have established a sensitive, specific and reproducible method for the simultaneous in situ detection of HBV-specific nucleotide sequences and antigens in paraffin-embedded liver tissue using nonradioactive hybridization and immunohistochemical techniques. Liver sections were stained for HBsAg or HBcAg by immunohistochemistry (IHC) using an enhanced biotinstreptavidin technique. Following immunohistochemical staining of the liver sections, in situ hybridization (ISH) was performed on the same section using a digoxigenin-labeled, HBV-specific probe. Specific hybridization was detected using an anti-digoxigenin, Fab fragment-alkaline phosphatase conjugate. This simultaneous assay permits the subcellular localization of HBV DNA and antigens with excellent preservation of tissue morphology and absence of background staining. In addition, the types and percentage of cells harboring HBV in the tissue can be determined. Although both reactions are detected by immunohistochemical methods, the application of a dual detection system using two different color reagents permits the identification of HBV antigens as a red signal and HBV DNA as a blue-purple signal at the single cell level. Both ISH and IHC can be performed in the same tissue section without significantly reducing the sensitivity of either assay. In addition, since this simultaneous detection assay can be completed within two days and eliminates the need for radioactive probes, it may be used effectively as a routine clinical procedure.

DNA Probes↗