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Biomedical subjects

J Crouch

Publications and source records attributed to J Crouch.

At least 19 recordsLinked to original sources

Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation.

Epstein-Barr virus (EBV)-specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV(+) individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8(+) T cells specific for lytic and latent cycle-derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell-depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations. (Blood. 2000;96:2814-2821)

Adult↗

Epstein-Barr virus RNA detection and glandular differentiation in nasopharyngeal carcinoma: report of 2 cases.

Most tumors arising in the nasopharynx are either squamous cell carcinoma or so-called undifferentiated carcinoma of the nasopharyngeal type. Primary adenocarcinomas of the nasopharynx are rare, and glandular differentiation in undifferentiated carcinoma of the nasopharyngeal type has not been reported to date. We report 2 cases of undifferentiated carcinoma of the nasopharyngeal type that show distinct glandular differentiation by light microscopy, histochemistry, immunohistochemistry, and ultrastructure. Both tumors showed equal positivity for Epstein-Barr virus latent membrane protein and in situ hybridization for Epstein-Barr virus genome in the undifferentiated areas of the tumor and those featuring glandular differentiation.

Adenocarcinoma↗

Evaluation of a telerobotic system to assist surgeons in microsurgery.

A tool was developed that assists surgeons in manipulating surgical instruments more precisely than is possible manually. The tool is a telemanipulator that scales down the surgeon's hand motion and filters tremor in the motion. The signals measured from the surgeon's hand are transformed and used to drive a six-degrees-of-freedom robot to position the surgical instrument mounted on its tip. A pilot study comparing the performance of the telemanipulator system against manual instrument positioning was conducted at the University of Southern California School of Medicine. The results show that a telerobotic tool can improve the performance of a microsurgeon by increasing the precision with which he can position surgical instruments, but this is achieved at the cost of increased time in performing the task. We believe that this technology will extend the capabilities of microsurgeons and allow more surgeons to perform highly skilled procedures currently performed only by the best surgeons. It will also enable performance of new surgical procedures that are beyond the capabilities of even the most skilled surgeons.

Evaluation Studies as Topic↗

Pediatric AIDS-associated lymphocytic interstitial pneumonia and pulmonary arterio-occlusive disease: role of VCAM-1/VLA-4 adhesion pathway and human herpesviruses.

Because the mechanisms of lymphocyte accumulation in the lungs of children with AIDS-associated lymphocytic interstitial pneumonia (LIP) are unknown, we studied the relative contributions of known adhesion pathways in mediating lymphocyte adherence to endothelium and the potential role of human herpesviruses in the expansion of these lesions. LIP was characterized by lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and infiltration of the pulmonary interstitium with CD8(+) T lymphocytes. In some individuals there was expansion of the alveolar septae with dense aggregates of B lymphocytes, many containing the Epstein-Barr viral (EBV) genome. Patients with concurrent EBV infection also demonstrated large-vessel arteriopathy characterized by thickening of the intimae with collagen and smooth muscle. Venular endothelium from the lung of children with LIP, but not uninflamed lung from other children with AIDS or lung from children with nonspecific pneumonitis, expressed high levels of vascular cell adhesion molecule-1 (VCAM-1) protein. In turn, inflammatory cells expressing very late activation antigen-4 (VLA-4), the leukocyte ligand for VCAM-1, were the predominant perivascular infiltrate associated with vessels expressing VCAM-1. Expression of other endothelial adhesion molecules, including intracellular adhesion molecule-1 and E-selectin, was not uniformly associated with LIP. Using a tissue adhesion assay combined with immunohistochemistry for VCAM-1, we show that CD8(+) T cell clones that express VLA-4 bind preferentially to pulmonary vessels in sites of LIP: vessels that expressed high levels of VCAM-1. When tissues and cells were pretreated with antibodies to VCAM-1 or VLA-4, respectively, adhesion was inhibited by >/=80%. Thus, infiltration of alveolar septae with CD8(+) T cells was highly correlative with VCAM-1/VLA-4 adhesive interactions, and focal expansion of B cells was coincidental to co-infection with EBV.

AIDS-Related Opportunistic Infections↗

Comparison of four real-time ultrasound systems that predict intramuscular fat in beef cattle.

Eighty-one crossbred steers were used to evaluate four commercially available ultrasound systems that predict intramuscular fat. The software systems represented included Animal Ultrasound Services, Inc., Ithaca, NY; CPEC, Oakley, KS; Critical Vision, Inc., Atlanta, GA (CVIS); and Classic Ultrasound Equipment, Tequesta, FL. Systems were evaluated using marbling scores and percentage ether extractable fat of the longissimus muscle. Before statistical analyses, system predictions were corrected for the respective system's average deviation between the prediction and carcass measurement. The absolute difference between system prediction and percentage ether extract (EEADIFF) or marbling score (MADIFF) converted to ether extract by regression was analyzed with a model accounting for effects of system, technician within system, animal, and animal x system. Steers with USDA marbling scores less than Small00 were assigned to a low marbling class, and all others were assigned to a second class. Data were then analyzed with a subsequent model including marbling class. For EEADIFF in the first model, system, animal, and system x animal were significant (P < .001). For MADIFF, technician within system (P < .05) and all other effects (P < .001) were significant. In the second model, system x marbling class was significant (P < .05) for EEADIFF and approached significance for MADIFF (P = .17). Least squares means for EEADIFF indicated that the systems were more precise measuring animals in the low marbling class. Finally, the CPEC and CVIS systems were the most precise for predicting intramuscular fat.

Adipose Tissue↗

Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD. METHODS: To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen. RESULTS: Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy. CONCLUSIONS: Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.

Acyclovir↗

Epstein-Barr virus suspension cell assay using in situ hybridization and flow cytometry.

We have developed a procedure for quantitative assay of Epstein-Barr virus (EBV)-infected cells in suspension in either latent or replicative phase using in situ hybridization and flow cytometry. The cells were hybridized with EBV-specific digoxigenin or biotin-labeled oligonucleotide probes, followed by binding to fluorescein-conjugated anti-digoxigenin or phycoerythrin-conjugated streptavidin, respectively. The cells hybridizing to the specific probes were quantitated by flow cytometry. A strong shift in fluorescence intensity (20-fold) was observed when the EBV-positive culture cells were hybridized with a specific EBER1 antisense probe. The sensitivity of the assay was at least one positive cell out of 9,000 beyond the normal control mean +/- 2 S.D. We performed two-color in situ hybridization/flow cytometry using probes to an EBV replication phase-specific mRNA and EBER1 on B95-8 cells in which a small portion (2-4%) of cells induce spontaneously into the replicative phase. In addition, we have developed a method for simultaneous analysis of the cell surface phenotype and EBV nucleic acid content in individual cells.

Cell Separation↗

Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.

Adult↗

Lymphomatoid granulomatosis of the skin and lung. An angiocentric T-cell-rich B-cell lymphoproliferative disorder.

OBJECTIVE: To test the recent hypothesis that lymphomatoid granulomatosis (LYG) is a clonal B-cell proliferative process related to Epstein-Barr virus (EBV). BACKGROUND AND DESIGN: Historically, LYG has been classified as an angiocentric T-cell lymphoproliferative disorder. To further characterize LYG in the skin, we analyzed for EBV RNA in lymphocytes using in situ hybridization, coupled with colabeling for B-cell and T-cell markers. Clonality of lymphocytes was assessed by polymerase chain reaction using primers for immunoglobulin heavy chain genes and T-cell receptor beta and gamma genes. SETTING: Academic referral center. PATIENTS: In a 5-year retrospective review, we identified 4 patients with classic clinical and pathologic features of LYG in skin and lung, and tissue available from both sites. MAIN OUTCOME MEASURES: The presence or absence of EBV RNA and clonal gene rearrangements in cutaneous and pulmonary lesions of LYG. RESULTS: Biopsy specimens of skin and lung in all patients revealed angiocentric infiltrates predominantly composed of T lymphocytes. Epstein-Barr virus RNA was identified in the skin of 1 patient and the lung of 3 patients, and was restricted to B cells. Polymerase chain reaction revealed clonal immunoglobulin heavy chain gene rearrangements and no clonal rearrangement of T-cell receptor genes in skin and lung tissue of all patients. CONCLUSIONS: At least some examples of LYG in the skin and lung are characterized by a clonal proliferation of B lymphocytes, some of which contain EBV RNA. The B cells are typically scarce and may be obscured by striking angiocentric T-cell infiltrates.

Adult↗

Intracranial pressure waveform indices in transient and refractory intracranial hypertension.

Analysis of data obtained by continuous computerized monitoring of intracranial pressure (ICP) in 109 adult patients with severe head trauma was performed to examine the pattern of change in indices of the ICP waveform. Indices derived from direct measurement of the ICP wave and obtained from a Fast Fourier Transform (FFT) were examined. Concurrent physiologic measurements were made. Two types of intracranial hypertension (ICH) were defined for comparison. 'Transient intracranial hypertension' occurred when an abrupt rise in ICP was followed by a return to below 25 mm Hg (n = 63). Increases in ICP that were progressive and led to neurologic deterioration and death were termed 'refractory intracranial hypertension' (n = 18). During transient ICH heart rate, arterial pressure, end-tidal carbon dioxide and jugular venous oxygen saturation all increased, while these measures either were unchanged or decreased during refractory ICH. The pulse amplitude of the ICP wave increased in both types of ICHtn. Other changes in the waveform indices were consistent with this change in pulse amplitude. HFC responded differently to the two types of changes, with an increase during the transient changes and a decrease during the refractory changes. The differences in changes in physiologic measurements as ICH occurred in the 2 groups suggest that in refractory ICH cerebral blood flow is maintained against the mounting ICP, while in transient ICH the hypertension is caused by an increase in cerebral blood flow. The waveform indices do not discriminate between the two types of changes.

Adult↗

Pilot study of current factors influencing the choice of psychiatry as a specialty.

OBJECTIVE: This is a time of major shifts in the perception of medical specialties. The authors have attempted to assess current attitudes of potential applicants for a residency in psychiatry. METHOD: Pilot interviews with fourth-year medical students at the University of California, San Francisco, led to the development of a questionnaire on factors influencing the choice of psychiatry as a specialty. The questionnaire was then sent to 113 fourth-year students with an identified psychiatric interest at nine schools. RESULTS: There was a response rate of 50.4%. The 54 students with a clear career decision had 22 of 38 item responses that significantly distinguished between those who matched in psychiatry and those who chose other specialties. CONCLUSIONS: Focused recruitment strategies are suggested based on answers to the questionnaire items.

Adult↗

Episodic excretion of ethanol during chronic intragastric ethanol infusion in the male rat: continuous vs. cyclic ethanol and nutrient infusions.

Continuous intragastric infusion of ethanol has been reported to result in episodic daily blood alcohol concentrations in male rats (Tsukamoto et al., 1985). We have used a total enteral nutrition (TEN) model to study the effects of chronic alcohol exposure on blood and urine alcohol concentrations in adult male Sprague Dawley rats (300 g). Two TEN models were studied: 1) the continuous model in which a complete diet was infused i.g. for 24 h/day; or 2) the cyclic model in which TEN was infused intragastrically for 12 h/day (i.e., only during the dark phase of the lighting cycle). In the continuous model, blood alcohol concentrations (BACs) were determined at 0900 h each morning and were found to vary from day to day in an episodic fashion, with values ranging from less than 10 mg/dl to greater than 500 mg/dl. The urine alcohol concentrations (UACs) were also episodic and closely tracked those of serum, such that the 24-h UACs were excellent predictors of the BACs taken at 0900 h. Both BACs and UACs increased from values below 10 mg/dl to greater than 500 mg/dl, and then decreased back to below 10 mg/dl with a mean peak-to-peak interval of 6 +/- 0.9 days. In the cyclic model, daily UACs were also episodic (i.e., had a daily variation) and very closely resembled those of the continuous model. We have proposed that ethanol metabolism during experimental intragastric ethanol infusion in the rat occurs via a system characterized by time-dependent pharmacokinetics.

Alcohol Dehydrogenase↗

Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats.

Intragastric infusion of ethanol to male rats as part of a system of total enteral nutrition allows chronic ethanol treatment without the nutritional and feeding problems associated with traditional liquid diets. Even though ethanol was infused at a constant rate 24 h a day, blood alcohol concentrations were observed to cycle over a 5- to 7-day period from values less than 10 mg/dl to greater than 400 mg/dl. Examination of the hepatic microsomal mono-oxygenase system in animals chronically treated with ethanol using this model revealed variable induction of cytochrome P450 CYP 2E1, the principal component of the microsomal ethanol oxidizing system. Correlations were observed between urine alcohol concentrations (UACs) and 1) the level of expression of CYP 2E1 mRNA in Northern blot analysis, 2) the level of CYP 2E1 apoprotein in Western blot analysis and, 3) microsomal p-nitrophenol (PNP) hydroxylation. The data from ethanol-treated animals were expressed as low UAC group (UACs < 200 mg/dl) and a high UAC group (UACs > 300 mg/dl) and compared to total enteral nutrition controls. In the low UAC group, a 6- to 7-fold induction in microsomal PNP hydroxylase (a CYP 2E1-dependent activity) was accompanied by a 4- to 5-fold increase in CYP 2E1 apoprotein, but no increase in CYP 2E1 mRNA levels. In contrast, in the high UAC group, induction of PNP hydroxylase was 15- to 16-fold, induction of CYP 2E1 apoprotein was 12- to 13-fold and CYP 2E1 mRNA was elevated 5- to 6-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗

The role of psychological factors in the report of building-related symptoms in sick building syndrome.

Sick building syndrome (SBS) is an increasingly common problem, although continued skepticism exists regarding its validity. Because of this, the attribution of complaints to psychogenic causes or mas hysteria persists. In this study (N = 111), self-report measures of psychopathology (Minnesota Multiphasic Personality Inventory [Hathaway & McKinley, 1983] and SCL-90-R [Derogatis, 1983]) and physical symptom reports failed to discriminate symptomatic from nonsymptomatic workers in an affected building but could more generally differentiate workers in the target building from control subjects. These results suggest that SBS cannot be justifiably attributed to psychological factors alone, although working in a contaminated environment appeared to have deleterious psychological consequences for some workers. Smoking history (in pack/years [packs per day x number of years smoked]) was reliably associated with the development of symptoms in exposed workers. Issues related to the assessment of psychological complaints in SBS are discussed.

Air Pollution, Indoor↗

Sick building syndrome.

"Sick building syndrome" (SBS) is one of the more colorful terms describing an increasingly common pattern of symptoms found among workers in modern office buildings. Core symptoms include lethargy, mucous membrane irritation, headache, eye irritation, and dry skin. To prompt a diagnosis of SBS, these otherwise common symptoms must be "excessively" reported and primarily "work-related." The World Health Organization now estimates that 30% of new or remodeled office buildings show signs of SBS, and that between 10% and 30% of the occupants of these buildings are affected by SBS. Despite such figures, SBS remains poorly researched and even more poorly understood. The following review provides the clinician an overview of SBS that will allow a more accurate differential diagnosis and will help to prevent the widespread suffering that can accrue when SBS is not quickly recognized.

Air Conditioning↗

Utility of the Seashore Tonal Memory Test in neuropsychological assessment.

This study assessed the diagnostic utility of the Seashore Tonal Memory Test in detecting and localizing cerebral lesions. A group of 238 subjects with focal or diffuse cerebral lesions and a group of 112 normal comparison subjects were administered the Seashore Tonal Memory Test and the Halstead-Reitan Battery. All brain-damaged subgroups did significantly worse than the normal group on the Tonal Memory Test. Patients with right-hemisphere lesions were more impaired on this test than were those with left-hemisphere lesions. In contrast, Seashore Rhythm Test scores were not significantly different for groups with right- versus left-hemisphere lesions. Tonal Memory performance was not found to be related to more precise location of structural lesions within the right hemisphere. Step-wise discriminate function analyses indicated that the Tonal Memory Test adds to the Halstead-Reitan Battery in discriminating left-hemisphere from right-hemisphere lesions and that, for this purpose, it was a better discriminator than all but one of the individual tests currently in the battery.

Adult↗

Preservation of neutrophils in CPD-adenine.

Human neutrophils were stored in vitro in CPD or CPD-adenine plasma under conditions designed to simulate those of leukapheresis followed by short-term preservation. Viability, morphology by light microscopy, and phagocytic ability of cells stored in either anticoagulant were similar when studied sequentially during 72 hours of storage. Thus, CPD-adenine offered no advantage, under the conditions employed, over standard CPD without adenine.

Adenine↗