Search PubMed⌕ Search

Biomedical subjects

L Alpert

Publications and source records attributed to L Alpert.

35 records · Page 2Linked to original sources

Morphometry and muscle gene expression in hypertrophied hearts from polyomavirus large T antigen transgenic mice.

Transgenic mice expressing polyomavirus large T antigen (PVLT) in cardiomyocytes develop a cardiac hypertrophy in adulthood. Morphometric analysis identified cardiomyocytes enlarged up to ninefold in cross-sectional area in the adult transgenic hearts compared with normal age-matched nontransgenic hearts. Most enlarged cardiomyocytes were found in the subendocardium, whereas normal-sized cardiomyocytes were localized to the midmyocardium. Transgenic hearts did not express detectable skeletal muscle actin mRNA or protein, or skeletal troponin I isoform mRNA. Some, but not all, transgenic hearts expressed an increase in the beta-myosin heavy chain mRNA. All five transgenic mice tested had increased expression of atrial natriuretic factor (ANF) mRNA. Whereas normal hearts expressed three myosin light chain proteins of 19, 16, and 15 kDa, we found that the 19-kDa myosin light chain was not observed in the transgenic hearts. We conclude that adult, PVLT-expressing, transgenic mice developed enlarged cardiomyocytes with an increase in beta-myosin heavy chain and ANF mRNA expression, but a widespread skeletal isoform usage was not present in these transgenic mice. The adult transgenic hearts thus display histological and molecular changes similar to those found in hypertrophy induced by a pressure overload in vivo.

Animals↗

Helicobacter heilmannii-like spiral bacteria in gastric mucosal biopsies. Prevalence and clinical significance.

BACKGROUND: Gastric Helicobacter pylori (Hp) is highly associated with histological gastritis and peptic ulcer disease, yet Helicobacter heilmannii (Hh, also known as Gastrospirillum hominis) may be a less frequent gastric pathogen about which less is known. PATIENTS AND METHODS: We evaluated 1223 gastric biopsies from 1042 upper endoscopies with biopsies performed over 1 year. Spiral bacteria were specifically sought in biopsies from 912 endoscopies. Clinical and pathologic data from patients with unusual spiral bacteria were tabulated and sera were evaluated for anti-Hp antibodies. RESULTS: The histologic prevalences of Hp and Hh-like bacteria were 59% and 0.5%, respectively, in 912 endoscopies. All four patients with Hh-like spiral bacteria had gastrointestinal symptoms and histologic gastritis. Two had immigrated from the Philippines and one from Belgium. Endoscopic findings and clinical course varied. One improved spontaneously; one improved following antibiotic therapy. One patient's symptoms and bacteria persisted without therapy. One patient coinfected with Hp was treated with apparent clearance of Hh but persistence of Hp. CONCLUSIONS: Helicobacter heilmannii-like bacteria can be distinguished from Hp with routine histologic stains; both bacteria are irregularly distributed. Helicobacter heilmannii appears to be a significant though uncommon cause of gastric inflammation. Some patients with Hh-like bacteria may benefit from anti-Hp therapy.

Adult↗

Clinical and histopathological variation in hepatocellular carcinoma.

OBJECTIVES: To assess clinical and histopathological variation in hepatocellular carcinoma from different endemic zones and to relate such variation to current putative pathogenic mechanisms of carcinogenesis. METHODS: Review of pertinent English language articles with emphasis on regional differences as they relate to our objectives. RESULTS: Clinical presentation of hepatocellular carcinoma is variable in different endemic zones. Such different features may depend on the interaction of different etiological initiators and, probably, promoters that can lead to different genetic aberrations. Similarly, there also may be histopathological variation. However, it is difficult to clearly delineate such differences, in part, because of lack of uniformity in reporting interpretation of histological data in the literature. And, the ethnic origin of patients is not always noted in middle and low endemic zones of hepatocellular carcinoma. CONCLUSIONS: Distinction in clinical and histopathological variation in hepatocellular carcinoma may benefit from delineating the ethnic origin of subjects included in studies and from adoption of clear uniform terminology for benign, indeterminate, and malignant lesions.

Carcinoma, Hepatocellular↗

A transgenic mouse line harboring a smooth muscle alpha-actin promoter polyomavirus middle T antigen transgene develops an epithelial hyperplasia in the rectum and distal stomach.

BACKGROUND: Transgenic mice are the product of the microinjection of foreign DNA directly into the pronuclei of a one-cell embryo. The foreign DNA can cause insertional inactivation or activation of the flanking genetic locus. EXPERIMENTAL DESIGN: We isolated five lines of transgenic mice harboring the chicken alpha-actin vascular smooth muscle enhancer/promoter linked to the polyomavirus middle T antigen using a standard microinjection protocol. The expression of the transgene was assessed in RNA prepared from affected and nonaffected tissue by RNase protection and reverse transcriptase-polymerase chain reaction analyses. Cell morphology was determined in stained sections from fixed tissues. RESULTS: In this article, we document the development of epithelial hyperplasia in the rectum and distal stomach together with female infertility in a single line of transgenic mice harboring the transgene. We were unable to demonstrate the expression of the transgene in any tissue examined, regardless of the degree of hyperplasia. The phenotype was present in the heterozygous state in both males and females. CONCLUSIONS: In the absence of the expression of the transgene, we conclude that the insertion of the transgene may have caused the epithelial hyperplasia directly or may have contributed to a condition that promotes hyperplasia. The transgene may have activated a dominant-acting neighboring gene.

Actins↗

Selection of the chimpanzee over the baboon as a model for Helicobacter pylori infection.

Baboons (Papio sp.) and chimpanzees (Pan troglodytes) were screened for the presence of Helicobacter pylori. The gastric mucosae of the baboons were colonized by large spiral bacteria. However, a group of adult chimpanzees were identified that were free of spiral gastric bacteria, with five animals being recruited into an H. pylori challenge study. These animals were inoculated orogastrically with one of four strains of H. pylori and followed for up to 26 weeks. H. pylori was established in one of these animals during a primary challenge and in two other animals on secondary challenge. It was shown that the chimpanzee can be infected with H. pylori and that the inflammatory response in these animals mimics that seen in humans. Infection was marked by an antibody response to H. pylori-specific antigens in two animals. It was observed that H. pylori antibody-negative chimpanzees had no apparent infection by H. pylori or related bacteria. Thus serological screening of chimpanzees can be used to identify candidate animals for further evaluation.

Animals↗

Calcium oxalate in breast lesions biopsied for calcification detected in screening mammography: incidence and clinical significance.

Two types of calcification have been reported in breast tissue: one appears as dark-blue deposits in routine histologic tissue sections and has been found to be composed mostly of calcium phosphate (CaP); the other is colorless and represents calcium oxalate (CaOx). CaP has been well characterized, but little is known about CaOx. The presence of CaOx was evaluated in 91 breast lesions (71 retrospective and 20 prospective cases) biopsied for the presence of calcification in screening mammography. CaOx was found in 36 cases (39%). CaOx is usually not clearly visible in routine histologic sections. CaOx is found as refractile, strongly birefringent crystals with characteristic morphology. CaOx was present only within benign lesions which frequently showed apocrine metaplasia. However, the breast tissue away from the areas with CaOx displayed a morphologic spectrum roughly similar to that in cases with CaP only. CaOx was clinically significant, i.e., actually represented the mammographic calcification, for which the biopsy was performed in 12% (11/91) of all cases studied and in 31% (11/36) of cases in which CaOx was found. In the cases where CaOx was not considered clinically significant, it was either not radiographically visible or, if visible, did not definitely represent the mammographic calcification for which the biopsy was performed. Since CaOx in breast biopsies is often clinically significant, and since CaOx is not clearly visible in routine sections, examination under polarized light is suggested for all breast biopsies removed for mammographic calcification, particularly when CaP deposits corresponding to the mammographic calcification are not apparent.

Adult↗

Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection.

This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection.

Adult↗

Cholesteatoma of the renal pelvis: endoscopic management.

We report 2 cases of renal cholesteatoma, 1 of which was associated with inactive renal tuberculosis and the other with urinary stone disease. Both cases were managed by endourological techniques. The diagnosis of cholesteatoma was suspected at ureteroscopic examination of the renal pelvis and it was confirmed by histological examination of biopsy material in both cases. Treatment consisted of endoscopic extraction of the keratinous debris from the collecting system. In 1 case this was achieved with the ureteroscope and in the other case the nephroscope was used.

Adult↗

Captopril-induced liver dysfunction.

We have described a patient with captopril-induced cholestatic jaundice. Captopril was confirmed as the causative agent, because jaundice occurred after administration of captopril and resolved quickly after administration was stopped.

Captopril↗

Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer.

DNA ploidy and percent of (%S-phase) S-phase cells were determined from the DNA content distribution of 21 benign and 76 malignant (69 primary, 7 metastatic) breast tumors using flow cytometry. All of the benign tumors were diploid, whereas 89% of the malignant tumors had measurable aneuploidy. Multiple stem-lines were observed in approximately 10% of the malignant tumors. The ploidy distribution of the malignant tumors was bimodal with an increased frequency of tumors with a near diploid DNA index (DI), and a second group with DI ranging from triploid to tetraploid. The percentage of cells in S-phase ranged from less than 1% to 37.4%. DI and %S were significantly higher in poorly differentiated duct carcinomas, medullary carcinomas, and recurrent tumor metastases. DI and %S were also significantly higher in estrogen-receptor-negative tumors. There was no correlation between DI or %S and the extent of axillary nodal metastases. However, within the groups of node-negative and node-positive patients, DI and %S were not randomly distributed but were significantly correlated with degree of nuclear differentiation. Both parameters were higher in poorly differentiated tumors compared with well-differentiated tumors, indicating significant intrastage heterogeneity in tumor ploidy and proliferation characteristics. Determination of the prognostic significance of DI and %S will require a longer follow-up time.

Breast Neoplasms↗

Composite mucinous ovarian neoplasms associated with Sertoli-Leydig and carcinoid tumors.

The authors describe two mucinous ovarian tumors that were hormonally active due to Sertoli-Leydig elements within the septal stroma. Carcinoid was also present in each case. The mesenchymal stromal cells within the septa of the mucinous tumors have undergone neoplastic proliferation with the Sertoli and Leydig differentiations, leading to the formation of arrhenoblastoma. The carcinoid component of these tumors is thought to have originated from argentaffin cells of the "intestinal" mucinous epithelium.

Adenocarcinoma, Mucinous↗

Gallium scintigraphy demonstration of an appendiceal mucocele: a proposed mechanism of uptake.

An appendiceal mucocele demonstrated intense early avidity for Ga-67, despite the lack of inflammatory cells to account for the uptake. It is proposed that the acid mucopolysaccharide component of the mucus within the lumen and lining cells accounted for the uptake of the gallium ion, in a similar manner to the uptake of its analogue, the ferric ion, as demonstrated by intense staining of mucus by the colloidal iron technique.

Aged↗

Overexpression of cytochrome P-450 isoforms involved in aflatoxin B1 bioactivation in human liver with cirrhosis and hepatitis.

Studies were carried out to test the hypothesis that inflammatory liver disease increases the expression of specific cytochrome P-450 isoenzymes involved in aflatoxin B1 (AFB) activation. The immunohistochemical expression and localization of various human cytochrome P-450 isoforms, including CYP2A6, CYP1A2, CYP3A4, and CYP2B1, were examined in normal human liver and liver with hepatitis and cirrhosis. The constitutive expression of CYP3A4 in normal liver showed a characteristic pattern of distribution in centrilobular hepatocytes, whereas CYP1A2, CYP2A6, and CYP2B1 were expressed uniformly throughout the liver acinus. In sections of liver infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the expression of CYP2A6 was markedly increased in hepatocytes immediately adjacent to areas of fibrosis and inflammation. CYP3A4 and CYP2B1 were induced to a lesser degree, and expression of CYP1A2 was unaffected. In HBV-infected liver, double immunostaining revealed that overexpression of CYP2A6 occurred in hepatocytes expressing the HBV core antigen. In HCV-infected liver, CYP2A6, CYP3A4, and CYP2B1 were overexpressed in hepatocytes with hemosiderin pigmentation. These results suggest that alterations in phenotypic expression of specific P-450 isoenzymes in hepatocytes associated with hepatic inflammation and cirrhosis might increase susceptibility to AFB genotoxicity.

Adult↗