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H Goldman

Publications and source records attributed to H Goldman.

At least 19 recordsLinked to original sources

Sucrase-isomaltase expression in chronic ulcerative colitis and dysplasia.

Sucrase-isomaltase (SI) is a mucosal disaccharidase that is present in normal small intestine and fetal colon. It also has been noted in colonic adenomas and adenocarcinomas. We used a polyclonal antibody to human SI to investigate enzyme presence and utility in detecting dysplastic changes in chronic ulcerative colitis. Sections from 32 cases were reviewed for the presence or absence of active colitis and dysplasia. Immunostaining of these cases for SI was performed and the results were reported based on location of immunoreactivity (ie, membrane and cytoplasmic staining in superficial and crypt epithelial cells) and percentage of positivity. Of 81 sections examined, 48 were rated negative for dysplasia (23 inactive colitis, 20 active, and five probably negative) and 28 were rated positive (eight low grade and 20 high grade). Surface membrane staining of epithelial cells was noted in all 28 dysplastic slides and positive cases (sensitivity, 100%) but also in 29 of 48 negative sections (P less than .001). In contrast, cytoplasmic positivity was present in 25 of 28 dysplastic and in only two of 48 negative slides (P less than .0001). The presence of cytoplasmic staining of SI in the superficial or crypt cells revealed a sensitivity of 92% and a specificity of 94%. There were five additional sections rated as indefinite for dysplasia (probably positive or unknown); two showed staining patterns typical of negative slides and three showed positive staining patterns. Of the 18 samples of transitional mucosa next to areas of dysplasia, surface membrane staining of SI was seen in all samples and cytoplasmic staining was seen in 15. We conclude that membrane staining of SI can be detected in inflammatory, regenerative, and dysplastic mucosa in ulcerative colitis. Cytoplasmic staining, however, correlates strongly with the presence of dysplastic change and may help in its detection.

Adult

Cerebrovascular responses to pentylenetetrazol: time and dose dependent effects.

The effects of subconvulsant and convulsant doses of pentylenetetrazol (PTZ) on cerebral blood flow (rCBF), permeability-capillary surface area products (rPS), and brain vascular spaces (BVS) were examined in 15 brain regions at 1 h, 24 h and 1 week after injection in male Sprague-Dawley rats. Brain histology was examined 3 days after injection. A dose of PTZ (50 mg/kg, i.p.), sufficient to trigger a single convulsive seizure, produced small regional changes in rCBF at 1 h, but not at 24 h or 1 week after injection. No significant changes in rPS or BVS were found at any time, and only mild histologic changes were observed. In contrast, a dose of PTZ (25 mg/kg) which failed to cause either convulsions or significant electrocorticographic changes, markedly increased rCBF and rPS. Some of these regional effects were still observed 1 week later. Similarly, more severe and extensive cellular changes followed treatment with the subconvulsive dose. These findings indicate that PTZ treatment can have prolonged effects on cerebrovascular functions and neuronal integrity even in the absence of convulsive activity.

Analysis of Variance

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Community Mental Health Services

Cerebrovascular changes in a rat model of moderate closed-head injury.

We have developed and tested a rat (Wistar) model of moderate concussion. Concussion is produced by controlled and repeatable mechanical fixed, closed-head injury. Moderate concussion in this model is characterized by 4 to 10 minutes of unconsciousness, absence of skull fractures or brain contusions, and few, if any, acute neurologic symptoms. By 2 hours postinjury, the subsequent trauma is further characterized by regional and global increases in cerebrovascular permeability and decreases in cerebral blood flow. Such changes are accompanied by brain swelling and two phases of elevated intracranial pressure; one lasting about 5 hours with a peak of about 10 mmHg, the other lasting more than 3 days postinjury with a peak of about 30 mmHg. Regional neurohistologic damage detected between 3 and 4 days postinjury correlates for the most part with earlier changes in regional permeability and blood flow. Significant morphologic changes which are characterized by patchy neuronal degeneration can be found in numerous forebrain locations, particularly in the frontal (coup) and entorhinal (contre coup) cortices. These observations have important parallels in human head trauma and suggest that this reliable physiological model may be a useful, relatively simple and inexpensive tool for investigating the mechanisms and therapeutics of head trauma.

Animals

Thymic epithelial cell transplantation in patients with acquired immunodeficiency syndrome. Evidence for infection by HIV-I of newly differentiated T cells at the site of transplantation.

From October 1983 to July 1984, 11 adult AIDS patients have received single or repeated thymic grafts. All have had opportunistic infections and 3 also had Kaposi's sarcoma. Thymic tissue from infants undergoing cardiac surgery was cultured to provide a thymocyte- and fibroblast-free epithelial cell inoculum. 18-21 days post-explantation, cells and explants were injected intraperitoneally, intramuscularly or intrahepatically. Transplants were well tolerated in all cases. In 7 cases liver biopsy was performed at the time of grafting and 2 months later. Ten patients have died after a mean survival time following transplantation of 8.7 months while 1 patient was lost to follow up. Clinical improvement and absence of new opportunistic infections were apparent for 4 months following transplantation. Partial immunoreconstitution was evidenced by an increase in peripheral blood lymphocytes (8 of 10 cases) and lymphocyte subsets (7 of 10 cases) as well as by presence of T4 and T8 positive cells in the liver (5 of 7 cases). In 5 of 7 patients, double-staining immunofluorescence showed that HIV-I antigens were present in T4-phenotype cells, at the site of the graft, 2 months after grafting, but were not detected in the liver at the time of grafting. Transient immunoreconstitution, therefore, maybe related to destruction of newly differentiated T lymphocytes.

Acquired Immunodeficiency Syndrome

Barrett's esophagus in children and young adults. Frequent association with mental retardation.

Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication.

Adolescent

Infection of human thymic lymphocytes by HIV-1.

We have succeeded in infecting human thymic lymphocytes with both the HIV-IIIB laboratory strain of HIV-1 as well as with a clinical isolate of this virus. Thymic lymphocytes were at least as susceptible to infection by HIV-1 as were cord blood lymphocytes, but appeared to display somewhat greater resistance to the cytopathic effects of the virus. As measured variously by each of indirect immunofluorescence for detection of viral p17, antigen capture assay for the presence of viral p24 in culture fluids, and levels of viral reverse transcriptase activity in culture fluids, infection of thymic lymphocytes could be detected as early as 2 days after infection by HIV-1, and persisted through at least 14 days of tissue culture maintenance. These findings suggest that thymic lymphocytes may be susceptible to infection by HIV-1 in vivo, and may also be relevant to our understanding of HIV-1-induced pathogenesis, particularly in pediatric populations.

Cells, Cultured

Allergy-related proctocolitis in infants: diagnostic usefulness of rectal biopsy.

To evaluate the diagnostic utility of rectal mucosal biopsies in infants with proctocolitis, we compared the clinical and histologic features of an allergy-related group (N = 36) with those of normal (N = 12) and inflammatory (N = 8) controls. Clinical features were nondiscriminatory among the three groups of patients, except for an increased absolute peripheral eosinophil count in the allergic group. Similarly, morphologic evidence of proctitis (cryptitis and crypt abscesses) and small or moderate numbers of eosinophils (less than or equal to 60 per ten high power fields) in the lamina propria of the biopsies did not discriminate among the three groups. However, large numbers of eosinophils (greater than 60 per ten high power fields) and eosinophils located in the muscularis mucosae or as the predominant cell in crypt abscesses were significantly associated with allergy-related disease. No histologic features of chronic colitis were noted in the allergy-related group. Thus, in tandem with the remainder of the clinical data, rectal mucosal biopsy is a useful adjunct in the diagnosis of allergic proctocolitis.

Biopsy

Replication of cytomegalovirus in human thymic epithelial cells.

Cytomegalovirus (CMV) has often been cited as a cause of immune suppression in children, yet little is known of the mechanisms through which this agent might affect immune function. We have succeeded in using CMV to productively infect cultured human fetal and infantile thymic epithelial (TE) cells. Morphological changes were apparent by 2-4 days after viral inoculation. CMV-related early antigen (EA) and late antigen (LA) were detected by immunofluorescence after 8 days, and progeny infectious CMV was recovered from culture media after 12-17 days. TE cells that reacted with monoclonal antibodies specific for keratin and for GQ ganglioside were predominant throughout the culture period. In contrast, infection by CMV resulted in a significant decrease in numbers of cells reactive with monoclonal antibodies specific for mesoderm-derived components. Inoculation of TE cells with CMV also caused a diminution in levels of detectable interleukin-1 (IL-1)-related antigen by 17 days after infection.

Animals

Infection of cultured human thymic epithelial cells by human immunodeficiency virus.

We have succeeded in growing the HTLV-IIIB strain of human immunodeficiency virus type 1 (HIV-1) in cultured human thymic epithelial (TE) cells. Expression of the HIV-1 proteins p17 and p24 was detected by immunofluorescence and reached a peak at 3 days after infection. Antigen capture and reverse transcriptase assays were used to detect HIV-1 in culture fluids, with positive results also being realized. The infection was cytolytic; cellular disarrangement, increased numbers of Hassall's corpuscles, and giant cells first appeared in monolayers of TE cells at 2 days after inoculation. By 4 days these changes were increased, and by 7 days, retraction and involution of TE cells were evident. The infection of TE cells by HIV-1 was blocked by preincubation with monoclonal OKT4A antibodies directed against CD4 target molecules.

Antibodies, Monoclonal

Effect of co-incubation with cytomegalovirus on growth of interleukin 2-dependent lymphocytes.

We have tested the ability of human cytomegalovirus (CMV) to interfere with the interleukin-2 (IL-2)-dependent proliferation of T lymphocytes in long-term tissue culture. The results indicate that CMV was able to establish an apparently abortive infection in approximately 40% of such cells, although productive viral replication could not be detected, and was able to impede cellular proliferation almost completely. The addition of high concentrations of exogenous IL-2 to cultures of CMV co-incubated cells was not readily able to overcome the anti-proliferation inhibitory effect induced by this virus. Exposure to CMV led to an approximate 50% decrease in the number of cells which expressed Tac Ag, or IL-2 receptor, at the cell surface.

Cell Division

Scanning electron microscopy of Barrett's epithelium and its correlation with light microscopy and mucin stains.

The surface epithelial cells of Barrett's esophagus were characterized using quantitative scanning electron microscopy and light microscopy with mucin histochemical stains. Fifty-one biopsy specimens of Barrett's esophagus from 15 patients and 31 control specimens of the stomach and intestines from 9 patients were examined. Three distinct surface cell types, in addition to the goblet cell, were recognized in Barrett's epithelium: the gastric-like cell in 31% of specimens, which was similar to the normal gastric surface cell by quantitative scanning electron microscopy; the intestinal-like cell in 41%, which was most similar to the normal small intestinal surface cell; and the variant cell in 80%, which had a range of surface features. By light microscopy, all specimens with variant and intestinal-like cells were classified as specialized columnar epithelium. The surface mucous cells in Barrett's epithelium displayed a variety of mucin staining patterns with acid nonsulfated (small intestinal-like) mucin present in 90% of specimens and acid sulfated (colonic-like) mucin in 43% of specimens. Quantitative scanning electron microscopy and mucin histochemical stains reveal a striking cellular heterogeneity not apparent by routine light microscopy.

Barrett Esophagus

Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9.

Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes.

Adrenocorticotropic Hormone

Sulcular exudate flow in gingival inflammation.

Sulcular exudate flow measurements were obtained from 45 subjects and compared to the clinical as well as histologic degrees of inflammation. The results of this investigation demonstrated no statistically significant difference between exudate flow and the clinical degree of inflammation while demonstrating a statistically significant difference between exudate flow and the clinical assessment of inflammation. It was proposed that current clinical indices do not accurately reflect the microscopic degree of gingival inflammation.

Gingival Crevicular Fluid