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H Goldman

Publications and source records attributed to H Goldman.

At least 73 records · Page 4Linked to original sources

Cerebrovascular responses to soman: time and dose dependent effects.

The effects of convulsant and subconvulsant doses of soman on cerebral blood flow (rCBF) and permeability-capillary surface area products (rPS) were examined in 15 brain regions at 1 hr, 24 hr and 1 week after injection in male, Sprague-Dawley rats. Brain histology was examined 3 days after injection. A convulsant dose of soman (70 micrograms/kg, sc) produced large increases in blood flow in all brain regions 1 hr after injection. Such elevations were still observed in 7/15 brain regions 1 day later and in 2/15 regions (septal area and basal ganglia) 1 week later. Similarly, rPS was significantly elevated in every brain region at 1 hr after injection, in 11/15 brain regions at 24 hr, and 4/15 regions 1 week later. Blood pressure peaked at 1 hr and remained well above control levels (115 mm Hg) for 5 hr after drug administration. A subconvulsant dose of soman (33 micrograms/kg) led to a significant, though less dramatic increase in blood flow in all brain regions within 1 hr but not at 1 day or 1 week after injection. In contrast, rPS increases were generally small except in hind-brain structures at 1 hr and 1 day after agent injection. By 1 week however, rPS values appeared to be rising generally and were significantly elevated in the olfactory bulbs and tubercle, as well as hindbrain regions. At this dose, blood pressures were unchanged from control levels (110-120 mm Hg) at all time periods. At 72 hr following injection of a convulsant dose of soman, severe and extensive cellular changes were found in 11/17 regions. After a subconvulsant dose, such abnormalities were still observed in 6/17 brain regions. The data strongly indicate that soman exposure can produce prolonged regional effects on cerebrovascular functions and neuronal integrity even in the absence of physiologic or behavioral evidence of seizure activity or sustained elevations of blood pressure.

Animals↗

Esophageal squamous papillomas. A clinicopathologic study of 38 lesions and analysis for human papillomavirus by the polymerase chain reaction.

The pathogenesis of esophageal squamous papilloma is not known, but chronic mucosal irritation and infection with human papillomavirus are two proposed etiologies. To investigate these hypotheses, we analyzed the clinical data and histological features of 38 esophageal squamous papillomas from 33 patients and performed the polymerase chain reaction technique for detection of several common human papilloma virus types on a subset of cases (n = 26) with sufficient available material. Clinically, males were affected more often than females (M:F ratio = 24:9); average age was 50 (range, 2-86 years). Most papillomas occurred singly (85%) and were located in the distal esophagus (70%). Patients with esophageal squamous papillomas, especially those with lesions in the distal esophagus, commonly had an associated chronic and often severe form of esophageal mucosal irritation such as esophagitis or Barrett's esophagus. Esophageal squamous papillomas were small polyps (average size, 0.5 cm) that we classified histologically into three types (exophytic, 50%; endophytic, 37%; spiked, 13%) based on the predominant shape of the squamous papillae. Fifty percent of the papillomas (13 of 26) tested, from 57% of patients (12 of 21), were positive for human papilloma virus, most commonly type 16 (nine of 13), less often type 16 and 18 together (3/13), and rarely type 6b/11 (1 of 13). We propose a multifactorial etiology in which the synergistic action of mucosal irritation and human papilloma virus may be necessary for the development of esophageal squamous papillomas.

Adolescent↗

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↗

Research resources.

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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 measles virus in cultured human thymic epithelial cells.

Measles virus can replicate in cultures of both infantile and fetal human thymic epithelial cells. Virus-induced cytopathology including syncytium formation was first evident around 24 hr after viral inoculation of these cultures. At the same time, the cultures began to lose their characteristic thymus-like organizational structure. Viral antigens were detected in infected cells by indirect immunofluorescence, and the presence of progeny virions was demonstrated in culture fluids.

Animals↗

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↗

Infection of cultured human fetal pancreatic islet cells by rubella virus.

A high incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in children and young adults previously afflicted with congenital rubella syndrome (CRS). The authors have studied the effect of rubella virus infection on human pancreatic islet cells in tissue culture. These experiments were performed with the use of both monolayers and free-floating human fetal islets of Langerhans tissue. Levels of production of immunoreactive insulin by islet cells that had been infected by rubella virus were lower than those observed in control cultures, under conditions of high glucose concentration (11.1 mmol/L) in the medium. The presence of rubella viral antigens in human pancreatic beta and non-beta cells was demonstrated by double-label immunofluorescence. These results suggest that rubella virus can infect human pancreatic islet cells and that such infection may lead to significant reductions in levels of secreted insulin.

Antigens, Viral↗