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Biomedical subjects

D A Katz

Publications and source records attributed to D A Katz.

At least 19 recordsLinked to original sources
PubMed1995

Fc gamma RII, Fc gamma RIII, and CD18 receptors mediate in part neutrophil activation on a plasma coated expanded polytetrafluoroethylene surface.

BACKGROUND: A biomaterial-induced polymorphonuclear neutrophil (PMN) defect may predispose the implanted vascular graft to infection. PMNs bind, activate, and undergo morphologic changes when exposed to uncoated or plasma coated expanded polytetrafluoroethylene (ePTFE) surfaces. The purpose of this study was to investigate whether the CD18 integrin receptor or the immunoglobulin receptors Fc gamma RII and Fc gamma RIII mediate either PMN binding or activation on ePTFE. METHODS: PMN binding and activation were determined after incubation of these cells on human immunoglobulin (IgG) or fibrinogen coated surfaces and uncoated or plasma coated ePTFE. PMN activation was measured by using the ferricytochrome reduction assay. Binding was determined with chromium 51-labeled PMNs. To block the Fc gamma RII, Fc gamma RIII, and CD18 receptors, PMNs were preincubated with the monoclonal antibodies (mAbs) IV.3, 3G8, and IB4, respectively. Irrelevant isotype matched mAbs were used as control. RESULTS: Monoclonal antibody IB4 inhibited binding of activated PMNs to fibrinogen coated surfaces. Binding to IgG was affected by either mAb IB4 or IV.3, but the greatest degree of inhibition was achieved when mAbs IB4 and IV.3 were used in combination. IgG-induced activation was partially inhibited by mAb IV.3 but was fully inhibited by a combination of mAbs IB4 and IV.3 The mAbs did not affect PMN binding to uncoated or plasma coated ePTFE, nor was PMN activation on the uncoated ePTFE surface inhibited. PMN activation on the plasma coated ePTFE surface was, however, partially inhibited by the combination of mAb IB4 with either mAb IV.3 or 3G8. CONCLUSIONS: A synergistic interaction between the PMN Fc gamma RII receptor and the CD18 integrin receptor accounts for surface bound IgG-induced cell activation. Both receptors also play a role in mediating PMN activation on the plasma-coated ePTFE surface.

Antibodies, Monoclonal↗
PubMed1995

Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

AIDS Dementia Complex↗
PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗
PubMed1995

Circle of Willis: evaluation with spiral CT angiography, MR angiography, and conventional angiography.

PURPOSE: To evaluate the use of spiral computed tomographic (CT) angiography in the analysis of the arteries of the circle of Willis and compare these results with magnetic resonance (MR) angiography and conventional angiography. MATERIALS AND METHODS: The results in 17 patients who underwent examination were prospectively studied in a blinded fashion. The presence or absence of the arteries of the circle of Willis was determined by using maximum intensity projection reconstructions from CT angiography and MR angiography. These results were compared with results from conventional angiography. RESULTS: Similar sensitivities were determined for CT angiography (88.5%) and MR angiography (85.5%); however, MR angiography was found to differ significantly (P = .005) from conventional angiography. No significant differences (P > .05) were found between the two modalities and conventional angiography in the detection of the anterior, middle, or posterior cerebral arteries or the anterior communicating artery. CONCLUSION: Spiral CT angiography is highly sensitive in the detection of arterial anatomy in the circle of Willis and is a reliable alternative to MR angiography.

Cerebral Angiography↗
PubMed1995

Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings.

PURPOSE: To evaluate and describe the neuroimaging findings of patients with neurosyphilis. METHODS: The neuroimaging studies of 35 patients with documented neurosyphilis were reviewed. Diagnosis was established in 34 patients with cerebrospinal fluid for a Venereal Disease Research Laboratory test, complemented by autopsy in 1 and brain biopsy in 1. All patients had reactive fluorescent treponemal antibody tests with absorption in their sera. Imaging studies included plain and contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, MR angiography, and conventional angiography. Imaging findings were also correlated with the relevant pathologic findings at autopsy in three additional patients with neurosyphilis who did not have brain imaging studies. RESULTS: Of the 35 patients with imaging studies, 32 tested human immunodeficiency virus (HIV)-seropositive, and 3 were HIV-seronegative. Eleven (31%) of 35 patients had normal radiographic findings. Cerebral infarctions were seen in 8 (23%) of 35 patients, and nonspecific white matter lesions in 7 (20%) of 35. Cerebral gummas and extraaxial enhancement indicating meningitis were noted in 2 (6%) of 35 patients, respectively. Arteritis was demonstrated in 2 (50%) of 4 patients who underwent either MR angiography or conventional angiography. The 3 subjects who had autopsy but not imaging studies were found to have manifestations of meningovascular syphilis, including syphilitic leptomeningitis and an obliterative endarteritis. CONCLUSION: We conclude that findings of vascular occlusive disease manifested as infarction or arteritis, enhancing cortical lesions with or without adjacent meningeal enhancement, focal or diffuse extraaxial enhancement, and white matter disease, although nonspecific, in the proper clinical setting should prompt appropriate testing for neurosyphilis, a treatable disease, in patients with and without HIV infection.

AIDS Dementia Complex↗
PubMed1992

Management of small abdominal aortic aneurysms. Early surgery vs watchful waiting.

OBJECTIVE: To compare two clinical strategies for the management of small abdominal aortic aneurysms (AAAs) less than 5 cm in diameter: early surgery (repair small AAAs when diagnosed) and watchful waiting (measure AAA size every 6 months and repair when the diameter reaches 5 cm). DATA SOURCES: We reviewed data from an earlier longitudinal study of patients with small AAAs to estimate incidence rates of rupture or acute expansion. Estimates for other parameters in the model were obtained by searching the medical literature (MEDLINE, 1966 to present). DATA SYNTHESIS: We constructed a Markov decision tree to compare early surgery with watchful waiting in patients with asymptomatic AAAs less than 5 cm in diameter, with respect to long-term survival in quality-adjusted life years. The average annual rates of rupture or acute expansion for AAAs with a maximal transverse diameter of less than 4.0, 4.0 to 4.9, and at least 5.0 cm, are 0, 3.3, and 14.4 events per 100 patient-years of observation, respectively. At an average rupture rate of 3.3 events per 100 patient-years and an average operative risk for elective surgery (4.6%, 30-day mortality), our model predicts that early surgery improves survival in patients who present with a 4-cm AAA. The benefit of early surgery decreases with increased age at presentation. If the average rupture rate for AAAs less than 5 cm is assumed to be low (eg, 0.4 event per 100 patient-years), watchful waiting if favored, particularly as operative risk increases. The decision in this subgroup, however, is sensitive to possible future increases in operative risk. CONCLUSIONS: In the majority of scenarios that we examined, early surgery is preferred to watchful waiting for patients with AAAs less than 5 cm in diameter. Watchful waiting is generally favored, however, for patients with a low risk of AAA rupture or acute expansion, including those patients who present with very small AAAs (eg, < 4 cm). More accurate data concerning the rupture risk of AAAs less than 5 cm would improve clinical decision making.

Aortic Aneurysm, Abdominal↗
PubMed1992

Viral proteins associated with the Epstein-Barr virus transactivator, ZEBRA.

The BamHI Z Epstein-Barr replication activator (ZEBRA) mediates disruption of latency and induction of Epstein-Barr virus (EBV) early gene expression in latently infected lymphocytes. Polyclonal rabbit sera raised against ZEBRA were used to immunoprecipitate ZEBRA-associated proteins (ZAPs). ZAPs of 19, 21, 23, and 42 kDa were coimmunoprecipitated with ZEBRA from extracts of EBV-producing lymphoid cell lines. ZAPs were not recognized directly by the rabbit sera, but they were antigenic for EBV+ human sera. Immunoprecipitation of ZAPs by ZEBRA-specific antisera required the presence of ZEBRA. ZAPs were not coprecipitated with ZEBRA from mouse cells expressing only ZEBRA, from Raji (a cell line in which EBV is unable to complete lytic replication), or from cells treated with inhibitors of viral DNA synthesis. Thus, ZAPs are late EBV-encoded proteins. ZEBRA and ZAPs colocalized to a salt-insoluble nuclear fraction, and both were found extracellularly in crude preparations of virions. ZAPs might function to affect the cellular localization of ZEBRA, to alter its capacity to transactivate, or to influence its target gene specificity.

Cell Line↗
PubMed1992

Transcriptional synergy by the Epstein-Barr virus transactivator ZEBRA.

ZEBRA is an Epstein-Barr virus (EBV) transcriptional activator that mediates a genetic switch between the latent and lytic states of the virus by binding to the promoters of genes involved in lytic DNA replication and activating their transcription. A computer survey revealed that 9 of 23 potential or known ZEBRA-responsive EBV genes contained two or more upstream binding sites; this suggested that ZEBRA can stimulate transcription synergistically. By using a series of synthetic promoters bearing one, two, three, five, and seven upstream recognition sites, we showed that ZEBRA activates transcription synergistically when templates bearing multiple sites were compared with a template bearing a single site. This phenomenon was observed in both uninfected and EBV-infected B-lymphoid cells and in vitro in a HeLa cell nuclear extract. DNase I footprinting was used to show that the synergy was not due to cooperative DNA binding mediated by direct contact between ZEBRA dimers. The in vitro experiments revealed two manifestations of synergy. One was seen when the levels of transcription observed with the same amounts of ZEBRA added to templates bearing different numbers of sites were compared. The other was observed when the two lowest concentrations of ZEBRA that stimulated measurable transcription from any given template were compared. On the basis of both the number of sites and the calculated Kd of ZEBRA for a single site, we estimated that the critical concentration of ZEBRA needed to elicit transcriptional synergy corresponds to a site occupancy of two or three bound ZEBRA dimers. Our results have biologic implications for both the EBV lytic cycle and other processes in which the concentration of an activator changes either temporally or spatially.

Base Sequence↗
PubMed1992

Magnetic resonance demonstration of intracranial CSF flow in children.

We determined the feasibility and value of studying intracranial CSF flow in children with potential CSF pathway problems using a cardiac gated cine magnetic resonance (MR) format. We studied 15 consecutive patients with a variety of clinical problems that suggested possible CSF pathway problems. The diagnoses included Chiari malformation, Dandy-Walker syndrome, external hydrocephalus, cerebellar tumor, CNS histoplasmosis, and tuberculous meningitis. In addition to documenting the feasibility of the technique in children (7 of 15 were less than 2 years of age), we derived significant new information relative to pathogenesis and/or therapy. The study provides preliminary evidence supporting intracranial CSF flow studies at the time of routine MR imaging of appropriate children.

Adolescent↗
PubMed1991

Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome.

BACKGROUND: Measurement of adrenocorticotropin levels in plasma from the inferior petrosal sinuses of patients with Cushing's syndrome can distinguish adrenocorticotropin-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion from an occult tumor. However, it is unknown whether such measurement consistently identifies patients with Cushing's disease and whether testing with corticotropin-releasing hormone (CRH) enhances the value of the procedure. METHODS: We prospectively studied 281 patients with Cushing's syndrome to evaluate the diagnostic efficacy of the procedure. Bilateral sampling was successfully accomplished in 278 patients, with no major morbidity; 262 of these patients underwent sampling before and after administration of ovine CRH. The adrenocorticotropin levels in the samples were used to calculate the ratio of the concentration in plasma from the inferior petrosal sinuses to the concentration in peripheral-blood plasma (the IPS:P ratio). RESULTS: The diagnosis of 246 patients was confirmed surgically as Cushing's disease in 215, as ectopic adrenocorticotropin syndrome in 20, and as primary adrenal disease in 11. An IPS:P ratio greater than or equal to 2.0 in basal samples identified 205 of the 215 patients with Cushing's disease (sensitivity, 95 percent), with no false positive results (specificity, 100 percent). A peak IPS:P ratio greater than or equal to 3.0 after CRH administration identified all 203 of the patients with Cushing's disease who received CRH (sensitivity, 100 percent), with no false positive results (specificity, 100 percent). The sensitivity was much lower when the adrenocorticotropin concentrations in the samples from one sinus were considered alone. In patients with Cushing's disease a difference of greater than or equal to 1.4-fold between the concentrations in the two sinuses (the adrenocorticotropin gradient) predicted the location of the microadenoma in 68 percent of 104 patients during basal sampling and in 71 percent of 105 patients after CRH administration. CONCLUSIONS: Simultaneous bilateral sampling of plasma from the inferior petrosal sinuses, with the adjunctive use of CRH, distinguishes patients with Cushing's disease from those with ectopic adrenocorticotropin secretion with high diagnostic accuracy.

ACTH Syndrome, Ectopic↗
PubMed1991

Clonal composition of pituitary adenomas in patients with Cushing's disease: determination by X-chromosome inactivation analysis.

The synthesis and secretion of anterior pituitary hormones are subjected to a variety of positive and negative feedback mechanisms. Aberrancies of these highly regulated phenomena may lead to hyperplasia involving multiple cells of the anterior lobe. Alternatively, a rare genetic mutation in a single cell may precede its clonal expansion. Which of these mechanisms is operative in the development of corticotroph adenomas is not known. To examine this question, we studied the clonal composition of ACTH-producing pituitary adenomas from female patients with Cushing's disease by using X-chromosome inactivation analysis. Nine of 27 patients examined were heterozygous at 1 of the 2 X-chromosome-linked polymorphic loci, hypoxanthine-phosphoribosyl-transferase and phosphoglycerate-kinase. The methylation patterns of the hypoxanthine-phosphoribosyl-transferase and phosphoglycerate-kinase genes, distinguishing between the active and inactive alleles, were analyzed in DNA extracted from the central part of the tumor and compared with those of autologous lymphocyte DNA. Six tumors (4 microadenomas and 2 macroadenomas) showed a single active allele of the X-chromosome-linked genes and were monoclonal in nature. The other 3 pituitary adenomas (1 microadenoma and 2 macroadenomas, 1 from a patient with Nelson's syndrome) revealed a polyclonal pattern of X-chromosome inactivation. Our data demonstrate that corticotroph adenomas of the pituitary may arise from a single cell or from more than one cell. Whether fundamentally different endocrine mechanisms underlie the two processes remains to be seen.

Adenoma↗
PubMed1991

Malignant clear cell hidradenoma: a case report and literature review.

Malignant clear cell hidradenoma is an uncommon variant of sweat gland tumors. Histological sections show lobulated masses and anastomising cords of cells which were polygonal to slightly fusiform in appearance. Most of the cells have bland appearing ovoid nuclei with slightly eosinophilic to clear cytoplasm. Focal areas within the lesion may show malignant changes. These areas may demonstrate large pleomorphic hyperchromatic nuclei, numerous mitotic figures, and a tendency toward squamous differentiation with many of the neoplastic cells demonstrating individual keratinization. Treatment is wide local resection. Consideration of regional lymph node dissection should be entertained because of the tendency to angiolymphatic spreads. Radiotherapy has not been shown to be helpful. Various chemotherapeutic regimens have been tried with inconclusive results. An illustrative case report is presented.

Adenoma, Sweat Gland↗
PubMed1991

Brain growth and cognitive improvement in children with human immunodeficiency virus-induced encephalopathy after 6 months of continuous infusion zidovudine therapy.

The ventricular area at the level of the foramen of Monro was measured from axial x-ray computed tomography (CT) scans obtained prior to and 6 months after the initiation of continuous infusion of zidovudine (ZDV) in eight children with human immunodeficiency virus-induced encephalopathy. Evidence of moderate to severe central atrophy was present on initial CT scans (p less than 0.05). Ventricular area and ventricular brain area ratio (VBR) decreased after ZDV therapy in seven of eight children (mean decrease of 21.5 and 20%, respectively, p less than 0.05). The degree of decrease in VBR correlated with reductions in cerebrospinal fluid (CSF) protein concentration (r = 0.93, p less than 0.01), but not lymphocyte T4 or T8 counts. Intelligence quotients (IQs) improved in all seven children tested (mean improvement of 17.7%, p less than 0.01) and correlated significantly with reductions in CSF protein concentration (r = -0.85, p = 0.003). The magnitude of IQ changes was not significantly correlated with the magnitude of changes in ventricular area. We conclude that the cognitive improvement of HIV encephalopathy seen after 6 months of continuous infusion of ZDV is accompanied by reduction in brain atrophy and decreased CSF protein, suggesting an ameliorating effect of ZDV on the pathogenesis of AIDS encephalopathy in children.

AIDS Dementia Complex↗
PubMed1990

Adoptive immunotherapy of intracerebral metastases in mice.

Lymphokine-activated killer (LAK) cells are a heterogeneous population of immune effector cells that nonspecifically destroy neoplastic cells but not normal cells. Although parenteral treatment with interleukin-2 (IL-2) alone or a combination of IL-2 and LAK cells reduces tumor load and prolongs survival in mice with pulmonary, peritoneal, or hepatic metastases, the effect of these treatments on brain metastases has not been studied. To determine in an animal model if intracerebral metastases would be protected by the immunologically privileged status of the brain, intracardiac and intravenous injections of 10(5) KHT sarcoma cells were performed in C3H mice to create brain and lung metastases, respectively. The mice were treated with adoptive immunotherapy to determine if efficacy seen in an extracerebral site could be reproduced in the brain, and if histological examination of these brains would reveal a significant degree of lymphocyte infiltration and cytolytic activity. Animals were treated with either parenteral IL-2 (7500 U three times daily on Days 3 to 7 after tumor injection), or IL-2 plus LAK cells (7500 U IL-2 times daily on Days 3 to 7, and 10(8) LAK cells intravenously on Days 3 and 6 after tumor injection), or IL-2 excipient (three times daily on Days 3 to 7 after tumor injection). As compared to control animals, pulmonary metastases on Day 14 after tumor injection were reduced or eliminated in animals treated with either IL-2 or IL-2 plus LAK cells (p less than 0.01). In these same animals, there was no reduction in the number of intracerebral metastases and no evidence of lymphocytic infiltration or cytolytic activity in the brain. This is the first study that reveals an organ-specific resistance to the treatment of metastases with adoptive immunotherapy, and affirms the concern that due to inadequate trafficking of endogenous or exogenous-activated lymphocytes or due to inadequate activation of in situ brain lymphoid precursors, there is no rejection of tumors in the brain. This information suggests that brain metastases in patients with systemic malignancies will not respond to intravenous treatment with LAK cells and IL-2, and that alternative forms of treatment are needed. Furthermore, this modification of a previously existing model of murine brain metastasis provides a method for concurrently evaluating the effectiveness of treatments for intra- and extracranial cancers.

Animals↗
PubMed1989

Neurosyphilis in acquired immunodeficiency syndrome.

In a retrospective study encompassing 42 months (January 1984 through July 1987), 12 patients were identified as having both neurosyphilis and acquired immunodeficiency syndrome. These patients constituted 44% of the entire group meeting rigorous diagnostic criteria for neurosyphilis and 1.5% of all patients hospitalized with acquired immunodeficiency syndrome. The typical patient with acquired immunodeficiency syndrome and neurosyphilis was young (mean age, 37 years) and male (83%). All had serological evidence of syphilis in both blood and cerebrospinal fluid. Syphilitic eye disease was surprisingly common in this group, occurring in 5 (42%). Four patients (33%) had been previously treated for syphilis. In 2, treatment for latent syphilis had been completed 3 and 5 months, respectively, before neurosyphilis was documented. Neurosyphilis is not uncommon in patients with acquired immunodeficiency syndrome in our population. In light of its diverse manifestations, syphilis should be considered in the differential diagnosis of any human immunodeficiency virus type 1-infected individual presenting with neurological, psychiatric, or ophthalmological disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A case of developmental right hemisphere dysfunction: implications for psychiatric diagnosis and management.

The authors present the case of an adult woman who was treated in the mental health system for many years for a syndrome of mixed anxiety and depression unresponsive to psychopharmacologic or psychotherapeutic treatment. A computed tomography scan revealed asymmetrical enlargement of the right temporal horn. This finding, as well as findings of severe difficulties in spatial relations together with mildly abnormal posturing of the left hand when walking (especially when the gait was stressed), suggested that the patient had a developmental disability of the right cerebral hemisphere. The authors conclude that because such patients might appear to have primarily psychiatric rather than neurologic problems, the diagnosis of right hemisphere dysfunction should be considered when the clinical presentation is indicative of atypical anxiety and affective disorders.

Anxiety Disorders↗