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Biomedical subjects

S D Finkelstein

Publications and source records attributed to S D Finkelstein.

At least 73 records · Page 4Linked to original sources
PubMed1994

Disease activity of hepatitis C correlates with single-stage polymerase chain reaction detection of hepatitis C virus.

Hepatitis C virus (HCV) RNA was amplified and detected in the serum of 17 anti-HCV antibody positive patients using a single-stage (30 cycles) polymerase chain reaction (PCR). Specific amplification, targeted to the C-100 protein (anti-HCV) region, was confirmed by direct sequencing of the PCR product. Single-stage PCR detected the virus in 11 patients. Polymerase chain reaction-positive patients demonstrated a significantly higher histologic activity index (10.3 + 1.2 standard error of mean [SEM] than those testing negative (5.8 + 1.5 SEM, P < .05). Nine of 11 PCR-positive patients exhibited a rise in alanine transaminase (ALT) values within 1 month of assay, compared with only 1 of 6 PCR-negative patients. The correlation between rising ALT levels and PCR positivity was significant (P < .01). Direct sequencing revealed mutability in all cases, some of which resulted in amino acid substitutions. The authors concluded that HCV detection using single-stage PCR correlates with biochemical and histologic features of disease activity. Mutability is likely an important feature of HCV pathobiology and may significantly affect detection methods.

Adult↗
PubMed1994

Postmortem magnetic resonance imaging of experimental spinal cord injury: magnetic resonance findings versus in vivo functional deficit.

The relationship between the severity of the posttraumatic functional deficit and findings on magnetic resonance imaging (MRI) was investigated in a rat model of experimental spinal cord trauma. Thirty Sprague-Dawley rats were subjected to an identical, moderate, contusion injury of the spinal cord. Control animals underwent laminectomy without cord injury. The severity of the functional deficit was assessed with the Combined Behavioral Score (CBS). Animals were killed at 3, 7, 14, 21, or 28 days after injury, and the fixed, excised spinal cords were studied with MRI at 1.9 T. The lesion length was measured on sagittal spin-echo MRI. The lesion length measured on MRI was highly correlated with the CBS functional score (r = 0.56, P = 0.002). There were significant correlations between lesion length as determined by MRI and by histological morphometry (r = 0.44, P = 0.02), between histological morphometric lesion length and CBS functional deficit (r = 0.76, P < 0.001), and between the area of residual white matter at the lesion epicenter, determined by histological techniques, and the severity of functional deficit (r = -0.59, P = 0.001). A qualitative estimate of the area of preserved white matter, derived from MRI, was significantly correlated with the severity of functional deficit (r = -0.56, P = 0.006). A multiple regression of MRI-determined lesion length and MRI estimate of residual white matter versus CBS explained more than 42% of the variability of the functional deficit among these animals subjected to the same weight drop injury. We conclude that MRI parameters are reliable predictors of the severity of neurological deficit in experimental spinal cord trauma.

Animals↗
PubMed1994

Histological characteristics and expression of acidic and basic fibroblast growth factor genes in intracerebral xenogeneic transplants of human glioma cells.

Eleven athymic nude rats had stereotactic intracerebral inoculation of cells from one of three established human glioma cell lines (A172, A1207, and A1235). The implants grew progressively in 9 of 11 instances, which led to spontaneous death of the host in 14 to 37 days. For comparison, two Sprague-Dawley normal albino rats were implanted with the rat C6 glioma cell line. One rat died at 14 days, and the other was killed at Day 16. The human glioma cells developed into partially (A172, A1235) or totally (A1207) circumscribed tumor masses. Invasion, when present, was manifested as infiltrating prongs of cells rather than as individual cell infiltration. The growth of the human glioma cells was accompanied by a small zone of surrounding edema and marked central necrosis. These features were not encountered in the C6 implants. Inflammatory changes were minimal to nonexistent in all cases. All tumor lines produced internal cerebral herniation and neuraxis spread with implants seeded throughout the ventricular system, often associated with ventricular dilation. In situ hybridization, by the use of isotopic and nonisotopic detection methods, was used to study the cellular expression of the acidic fibroblast growth factor and basic fibroblast growth factor genes in A172 glioma xenografts. The expression of these genes was not seen in normal rat brain, but the genes were selectively overexpressed by the glioma cell implants, with especially high signal in the tumor periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type.

BACKGROUND: New measures enabling better prediction of biologic behavior of large bowel cancer are highly desirable. One hundred ninety-four consecutive primary, recurrent, and metastatic colorectal adenocarcinomas, accessioned during 1991 at Rhode Island Hospital, were classified according to the presence and specific type of K-ras-2 point mutation. METHODS: An integrated histopathologic-genetic approach was used to detect mutations starting with minute, topographically selected, tissue samples from formaldehyde-fixed, paraffin-embedded specimens. RESULTS: Each colorectal adenocarcinoma exhibited either no or only one of seven specific types of K-ras-2 mutation. The mutation type of each primary tumor was present consistently in its metastatic deposits. Thirty-five percent of primary colorectal adenocarcinomas were found to be mutated (42 of 119). A significantly higher mutation rate (65%) was seen in lymphogenous-hematogenous metastases as a group (35 of 54; P < 0.005). By contrast, 22% of anastomotic recurrences and transcoelomic metastasis were mutated (4 of 18). Twenty-eight percent of adenocarcinomas with invasion limited to muscularis propria (Tis, T1, T2) were mutated (16 of 57), compared to 41% for more deeply invasive tumors (T3, T4; 26 of 63). When colorectal adenocarcinomas were analyzed by specific K-ras-2 mutation type, it was found that codon 13 mutated tumors did not progress to local or distant metastasis (P < 0.01). Tumors having a codon 12 valine substitution did not metastasize beyond pericolonic-perirectal lymph nodes. In contrast, colorectal cancers with codon 12 aspartic acid substitutions accounted for most of the distant hematogenous deposits (P < 0.01). Tumors with normal K-ras-2 accounted for most intraperitoneal deposits. CONCLUSIONS: Genotyping of colorectal adenocarcinoma by K-ras-2 status can identify subsets of patients likely to pursue indolent and aggressive forms of disease. The integrated histopathologic-genetic approach outlined is feasible for use in diagnostic pathology, providing information that together with clinicopathologic staging may individualize and optimize treatment.

Adenine↗
PubMed1993

Determination of tumor aggressiveness in colorectal cancer by K-ras-2 analysis.

Markers that predict tumor aggressiveness on a case-by-case basis would enable individualization and optimization of oncologic therapy. To achieve this goal, the presence and specific type of K-ras-2 point mutation was determined from formalin-fixed, paraffin-embedded tissue sites in 247 primary and 166 metastatic-recurrent colorectal adenocarcinomas, using a novel approach consisting of topographic tissue selection, DNA amplification, and direct sequencing applicable to large and needle-biopsy-sized specimens. The results provide the basis for a genotypic classification of colorectal cancer capable of predicting individual tumor aggressiveness, including the pattern and extent of metastasis.

Adenocarcinoma↗
PubMed1993

Late recurrence of ductal carcinoma in situ at the cutaneous end of surgical drainage following total mastectomy.

A 40-year-old woman underwent upper outer quadrantectomy breast biopsy which revealed extensive intraductal carcinoma, predominantly comedocarcinoma type, with high nuclear grade. Involved ducts were transected at the edge of the biopsy. Total mastectomy with low axillary lymph node dissection was performed 2 weeks later, showing residual intraductal carcinoma in the upper inner quadrant and no evidence of metastasis. Eight years later, the patient developed two separate foci of recurrent, invasive ductal carcinoma at the exit sites for mastectomy drainage in the subcutaneous skin of the upper abdomen. The mastectomy scar was clinically free of tumor. The biological basis for this unusual sequela of treated intraductal carcinoma is discussed together with its importance for management of early breast cancer.

Axilla↗
PubMed1992

Expression pattern of alpha-protein kinase C in human astrocytomas indicates a role in malignant progression.

Protein kinase C (PKC) is a family of isoenzymes which play an important role in regulating cell proliferation and differentiation. Constitutive activation of PKC, either by phorbol esters or overexpression of specific isoenzymes, leads to growth abnormalities in vitro and tumor promotion in vivo. Since stimulation of PKC in cultured astrocytes results in biochemical and morphological alterations associated with the transformed phenotype, we wanted to determine whether abnormal expression of specific isoenzymes of PKC was important in development of human astrocytomas in vivo. We have detected a specific pattern of alpha-PKC expression in human astrocytomas which is noteworthy because the highest transcript levels were detected in well-differentiated (Grade 1) tumors, with intermediate expression in anaplastic (Grade 2) astrocytomas and low or nondetectable levels in glioblastomas (Grade 3 astrocytomas) and normal controls. In comparison, the beta-PKC transcript was not detected in any of the tumors, while the gamma-PKC transcript was present in only one Grade 2 tumor. Immunohistochemistry, using a monoclonal antibody to alpha-PKC, revealed diffuse, positive cytoplasmic signals in most cells of the Grade 1 tumors. Grade 2 tumors exhibited heterogeneity of alpha-PKC expression, although a significant percentage of cells showed positivity. In contrast, only a small number of differentiated cells within Grade 3 tumors were positive for alpha-PKC expression, with the more malignant, dedifferentiated cells uniformly negative. Throughout all tumor grades, the staining pattern of alpha-PKC closely paralleled that of glial fibrillary acidic protein. Taken in conjunction with the established role of PKC in tumor promotion, these results suggest that the alpha-PKC isoenzyme plays a specific role in facilitating clonal expansion of transformed astrocytes in low-grade astrocytomas. Analysis of alpha-PKC may therefore serve as a direct biological marker of malignancy which may serve to enhance the current histopathological grading system.

Astrocytes↗
PubMed1991

Naloxone and experimental spinal cord injury: effect of varying dose and intensity of injury.

We have reported previously that high-dose (10 mg/kg) and megadose naloxone (as high as 150 mg/kg) failed to promote recovery of motor function after spinal cord injury in rat. In view of these negative results, in comparison to some reports of benefit of naloxone in the literature, the present study was undertaken to assess lower doses, using a modified 3 x 4 factorial design, to evaluate a range of lower doses in relation to various intensities of cord injury. Sprague-Dawley rats were assigned randomly to 10 groups (n = 10) relating to two factors: intensity of injury and dosage of naloxone. A dynamic-load injury was induced with a 10-g weight dropped from a height of 2.5 cm, 5.0 cm, or 17.5 cm. Animals were treated with naloxone 1 mg/kg, 4 mg/kg, 10 mg/kg, or saline (control). Tests of motor recovery were carried out weekly for 4 weeks postinjury. Histopathological morphometric analysis of the spinal cords was carried out for measurement of residual gray and white matter at the epicenter of the cord injury. In general, the behavioral data showed no improvement in recovery of function, with the possible exception of naloxone at a dosage of 4 mg/kg (not statistically significant at 4 weeks). Independent of naloxone treatment, there was a significant difference among the three intensities of injury. Pathologically, a difference could not be demonstrated in relation to dosage of naloxone, but as in the case of the behavioral data, a graded response occurred as a function of intensity of injury.

Animals↗
PubMed1990

Induction of heterotypic virus resistance in adult inbred mice immunized with a variant of Coxsackievirus B3.

Infection of adult male C3H/HeJ mice with a host range variant of Coxsackievirus B3 (CB3W-RD) induced resistance in these mice to an otherwise lethal dose of Coxsackievirus B1 (CB1). The protective effect induced by CB3W-RD was detectable as early as 1 day post-vaccination and was still present 10 weeks later. While untreated mice infected with CB1 died within 5 days because of massive hepatic necrosis, the liver was spared in mice immunized with CB3W-RD and then challenged with CB1. In general, CB1 titers in heart, liver, and pancreas of CB3W-RD-vaccinated animals were lower than that found in unvaccinated animals. Virus neutralizing antibody was not a mediator of this heterotypic, virus-induced protective effect. In addition, the outcome of CB1 infection could be modified if superinfection with CB3W-RD took place within 1-4 days following CB1 infection. In this regard, maximum therapeutic efficacy was observed when CB1 infected mice were superinfected 2 days after CB1 infection. CB1-infected mice that survived as a result of treatment with CB3W-RD exhibited liver regeneration but did develop myocardial necrosis.

Animals↗
PubMed1990

Experimental spinal cord injury: qualitative and quantitative histopathologic evaluation.

This study involved a morphometric analysis of an experimental model of spinal cord injury. The spinal cords of rats were injured by a weight drop at T8 level. Animals were sacrificed 4 weeks after injury, and histopathologic examination of the spinal cords was carried out qualitatively and also quantitatively with the aid of computer-assisted morphometry. Total cross-sectional areas of residual gray and white matter were determined at five regularly spaced intervals through the injured cord segment. The histologic findings were correlated with height of weight-drop and motor recovery in the hind limbs at 4 weeks postinjury. The weight-drop injury was found to produce a longitudinally asymmetrical cavitary defect, which was better assessed by a series of cross-sectional profiles than by a single histologic cross-section through the epicenter (site of maximal impact) of the cord injury. There was a strong correlation between height of weight-drop and amount of residual tissue (gray and white matter) at the epicenter. A correlation was also found between height of weight-drop and a composite of residual tissue evaluated at multiple levels through the injury site. By comparison with cross-sectional morphometry at the epicenter, multiple cross-sections, reflecting volume of residual tissue in the longitudinal extent of injury, showed greater statistical correlation with functional (behavioral) outcome. This "volumetric" assessment of the total region of injury is therefore recommended as preferable to a histopathologic evaluation limited to the epicenter.

Animals↗
PubMed1989

Heterogeneity of intraductal carcinoma of the breast.

Fifty-one women (29 to 75 years of age) with 55 cancers (ductal carcinoma in situ [DCIS] or ductal carcinoma in situ with microinvasion [DCISM] were studied by comparing biopsy specimens with mastectomy specimens. Presentation, histologic type, nuclear grade, microscopic duct counts, multicentricity, and microinvasion were correlated. Forty-seven percent of the cancers (26 of 55) were detected by mammography, 18% (ten of 55) were incidental to benign disease, and 35% (19 of 55) were palpable or exhibited nipple abnormality. Incidental tumors were all DCIS, averaged seven ducts, and showed no residual tumor during mastectomy. Mammographic lesions averaged 117 ducts (31% [eight of 26] were DCISM and 42% [11 of 26] were multicentric). Most comedocarcinomas that showed a high incidence of microinvasion were in this group. Clinical lesions averaged 110 ducts (42% [eight of 19] were DCISM and 68% [13 of 19] were multicentric). Three had nodal metastases. Mammographic and clinical tumors in the quantitative range of the incidental group (50 ducts) showed significant differences from it for all variables studied. Histologic and quantitative study of these tumors is necessary to best guide treatment. Incidental tumors, however, may only need observation.

Adult↗
PubMed1989

Cerebral Pseudallescheria boydii infection: unique occurrence of fungus ball formation in the brain.

Pseudallescheria (Petriellidium) boydii is the most frequent etiologic agent of mycetoma in temperate regions of the world. In addition, it may also occur as a systemic infection in immunocompromised patients. Infection of the central nervous system is rare, and only eleven cases of Pseudallescheria brain abscess have been documented. We report a leukemic patient in whom disseminated pseudallescheriasis was diagnosed only after death. This case is unique in that a white matter cavitation was present containing a fungoma of Pseudallescheria, the first report of a cerebral fungus ball caused by this organism. The previous cases of Pseudallescheria brain abscess are reviewed, and the histopathologic features of Pseudallescheria which permit its differentiation from Aspergillus and other fungi are discussed.

Adult↗
PubMed1988

Pathogenesis of acute myocardial necrosis in inbred mice infected with coxsackievirus B3.

The pathogenesis of myocardial necrosis due to CB3W infection was studied in BALB/c and C3H/HeJ mice. BALB/c mice infected with 5 x 10(4) pfu were found to die of massive hepatic coagulative necrosis before myocardial changes occurred. Reducing the inoculum size to 5 x 10(2) pfu resulted in sublethal hepatic involvement and multifocal myocardial coagulative necrosis by day 7 p.i. In contrast, C3H/HeJ mice survived infection and developed multifocal myocardial coagulative necrosis, but not liver disease following inoculation with as much as 5 x 10(6) pfu of CB3W. As with BALB/c mice infected with 5 x 10(2) pfu, myocardial lesions became apparent in C3H/HeJ mice a few days after peak cardiac virus titer was attained. Minimal inflammatory infiltrate was seen following development of cellular necrosis and was restricted to the areas of virus-induced pathologic change. However, no evidence was found for virus-specific cytotoxic T cell activity or for delayed type hypersensitivity responses. Furthermore, myocardial necrosis in CB3W-infected, T cell-depleted C3H/HeJ mice was as severe as in CB3W-infected, immunocompetent mice. These data have led us to conclude that cardiac lesions were due to virus-induced cytopathology rather than immunopathogenic mechanisms.

Animals↗
PubMed1988

Fat embolism to the cardiac conduction system associated with sudden death.

During a brief hospital stay, a patient under treatment with corticosteroids for lymphoma died suddenly and unexpectedly. At autopsy, fat emboli were identified in the lungs, myocardium, liver, and brain. Examination of the cardiac conduction system revealed fat emboli in the vessels of the bundle of His as well as those accompanying the bundle branches, a finding believed to have resulted in the sudden death. This report is the first of fat embolization to the cardiac conduction system and emphasizes the importance of examination of this system in cases of unexplained or sudden death.

Bundle of His↗
PubMed1988

Models of spinal cord injury: Part 3. Dynamic load technique.

Having previously studied a static load model of cord injury in rats, we report here an evaluation of a dynamic (weight drop) technique. Under general anesthesia, Sprague-Dawley rats were subjected to a laminectomy at T12, after which a 10-g weight was dropped onto a force transducer and impounder resting on the spinal cord; the weight drop distances varied in different groups from 0 (control) in increments of 2.5 cm to a maximal height of 17.5 cm. A strain gauge attached to the force transducer yielded an oscilloscopic wave form from which force of impact (peak force and impulse) was calculated. Eighty-six animals were used in this parametric study. The animals were observed for 4 weeks postinjury with two tests of motor recovery (Tarlov score for locomotion and the inclined plane test). After sacrifice at 4 weeks, the spinal cords were removed and, with the use of preset criteria, qualitative histopathological scoring of the extent of tissue damage was carried out. We found that the variable height of weight drop was capable of producing a graded injury that correlated with the force of injury (as measured by the force transducer) and with the outcome parameters of functional recovery and degree of morphological damage in the spinal cord. Histopathologically, there was a tendency to central cavitation of the cord. Both the static load and the dynamic load techniques seem to be valid models of spinal cord injury. Pathologically, however, the tissue damage after static load injury involved primarily the dorsal half of the cord. By contrast, the dynamic load technique produced central cavitation comparable to that observed in human spinal cord injury. In this respect, the dynamic model seems to be superior and its use is therefore recommended for studies of therapeutic intervention for spinal cord injury.

Animals↗