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Robert Jackson

Publications and source records attributed to Robert Jackson.

At least 19 recordsLinked to original sources
PubMed2025

Blood phenylalanine lowering partially reverses white matter changes in a mouse model of phenylketonuria.

Phenylketonuria (PKU) is a genetic defect caused by lack of the liver enzyme phenylalanine hydroxylase (PAH). This deficiency results in elevated blood phenylalanine (Phe) levels and neurotoxicity, which is manifested by reduced brain size, lower neurotransmitter levels, and reduced myelination. The goal of this study was to investigate brain myelination defects and their reversibility upon blood Phe lowering by analyzing the corpus callosum (CC) of adult Pahenu2 (PAH-deficient) mice. MRI and immunostaining demonstrated a significant reduction in CC volume in Pahenu2 mice. Treatment with an adeno-associated vector (AAV) encoding mouse PAH for 3.5 months improved but did not completely normalize CC volume. Total cholesterol, a major component of myelin, was unchanged in the CC of Pahenu2 mouse, while some sterol intermediates were significantly reduced by treatment. Single-nuclei transcriptomics showed an upregulation of oxidative stress-related pathways and increased expression of transthyretin, ApoE, Cst3, and Cd81 in CC in Pahenu2 mice. Normalization of blood Phe restored gene expression to levels comparable to those of heterozygous mice and was associated with the generation of differentiated myelin-producing oligodendrocyte subtypes and neuroprotective astrocytes. In summary, Pahenu2 mice showed white matter abnormalities and changes in transcriptome and sterol profiles, which were partially corrected by the normalization of blood Phe.

Animals↗
PubMed2006

Worsening of asthma with systemic corticosteroids. A case report and review of literature.

Despite widespread use for treatment of asthma and allergies, glucocorticoids may cause allergic reactions, even anaphylaxis. The incidence of adverse reactions to systemic glucocorticoids is 0.3%. The most commonly reported corticosteroids causing anaphylaxis like reactions are hydrocortisone, prednisone, and methylprednisolone. Most authors agree that allergic reactions to systemic corticosteroids are possibly immunoglobulin E mediated. We report a patient with asthma, aspirin allergy, and nasal polyps who developed bronchospasm following the administration of intravenous methylprednisolone sodium succinate during an acute asthmatic attack. We discuss the differential diagnosis of worsening asthma despite adequate treatment, and suggest corticosteroid-induced bronchospasm in our patient. Corticosteroid-induced bronchospasm should be considered when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy, particularly when a history of aspirin allergy is present. TEACHING POINT: Know the differential diagnosis for worsening of asthma despite adequate treatment. Consider corticosteroid-induced bronchospasm when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy. Corticosteroid-induced bronchospasm is more commonly seen in asthmatics with a history of aspirin allergy.

Aspirin↗
PubMed2006

Course of weaning from prolonged mechanical ventilation after cardiac surgery.

In order to determine the temporal pattern of weaning from mechanical ventilation for patients undergoing prolonged mechanical ventilation after cardiac surgery, we performed a retrospective review of 21 patients' weaning courses at our long-term acute care hospital. Using multiple regression analysis of an estimate of individual patients' percentage of mechanical ventilator support per day (%MVSD), we determined that 14 of 21 patients (67%) showed a statistically significant quadratic or cubic relationship between time and % MVSD. These patients showed little or no improvement in their ventilator dependence until a point in time when, abruptly, they began to make rapid progress (a "wean turning point"), after which they progressed to discontinuation of mechanical ventilation in a relatively short period of time. The other 7 patients appeared to have a similar weaning pattern, although the data were not statistically significant. Most patients in the study group weaned from the ventilator through a specific temporal pattern that is newly described herein. Data analysis suggested that the mechanism for the development of a wean turning point was improvement of pulmonary mechanics rather than improvement in gas exchange or respiratory load. Although these observations need to be confirmed by a prospective trial, they may have implications for weaning cardiac surgery patients from prolonged mechanical ventilation, and possibly for weaning a broader group of patients who require prolonged mechanical ventilation.

Adult↗
PubMed2005

Primary bladder lymphoma: management and outcome of 12 patients with a review of the literature.

Primary bladder non-Hodgkin's lymphoma (NHL) is rare. Optimal management remains controversial. Using the Scotland and Newcastle lymphoma group database, 12 patients with primary bladder lymphoma were identified between 1980 and 2001, the largest single group of patients available to date. Histology and immunocytochemistry was reviewed in 9 of the 12 cases. Six cases were low-grade extranodal marginal zone lymphoma, 4 diffuse large B-cell lymphoma, one an ALK 1 positive anaplastic large cell lymphoma (ALKoma) and one a low-grade lymphoma unspecified. Two patients (low-grade NHL) were treated with oral antibiotics (n=1) or diathermy (n=1) alone with complete resolution of disease. One patient with high-grade NHL gained complete remission without conventional therapy. Nine patients were treated with single or combined modality surgery, chemotherapy and/or radiotherapy. Overall survival was 75%, mean follow up of 4.8 (range 1-10) years. A review of 88 additional cases in the literature support the findings that primary bladder lymphoma is associated with a good prognosis. Patients with low-grade extranodal marginal zone lymphoma may respond well to simple therapies. Patients with diffuse large B-cell lymphoma respond well to first-line chemotherapy regimens. Ureteric obstruction and acute renal failure are serious complications. Repeat cystoscopy is mandatory for follow-up.

Adult↗
PubMed2005

Phenotype and frequency of Epstein-Barr virus-infected cells in pretreatment blood samples from patients with Hodgkin lymphoma.

An accumulating body of data suggests that the Epstein-Barr virus (EBV), a lymphotropic herpesvirus, is involved in the pathogenesis of a proportion of cases of Hodgkin lymphoma (HL). In this study, we showed that the frequency of circulating EBV-infected cells was significantly higher (P < 0.001) in pretreatment blood samples from EBV-associated cases when compared with non-EBV-associated cases. We further showed that in patients with EBV-associated disease, the virus persisted in the peripheral blood in memory B cells. This phenotype is consistent with that seen in healthy seropositive controls, post-transplant patients and patients with acute infectious mononucleosis. The data suggest that an increased frequency of EBV carrying B cells in peripheral blood is associated with EBV-associated HL.

Adolescent↗
PubMed2004

CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status.

Human immunodeficiency virus (HIV) disease is associated with loss of CD4(+) T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4(+) T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25(+)CD4(+) regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25(+)CD4(+) T cells significantly suppressed cellular proliferation and cytokine production by CD4(+) and CD8(+) T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-beta independent. Individuals with strong HIV-specific CD25(+) T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4(+): CD8(+) T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25(+)CD4(+) T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease.

CD4 Antigens↗
PubMed2004

Scabies by Kenneth Mellanby.

BACKGROUND: Epidemics of scabies are often associated with wars or other times of social upheaval. This was particularly evident during the Second World War when it was estimated that there were one to two million patients with scabies in Great Britain. OBJECTIVE: This article reviews the work of the zoologist Kenneth Mellanby of England and evaluates his contribution to our knowledge of the diagnosis and treatment of scabies in the Second World War. CONCLUSION: Using humans, Mellanby studied the transmission and treatment of this disease. Among his contributions were knowledge of how many mites the average patient had, and where they were located. He clearly noted and described that the scabies rash was not limited to the location of the mites on the body; he attributed the rash in areas with no mites to "a true sensitization." He found that "fomites were not the major method of transmissions.

England↗
PubMed2004

Neonatal natural killer cells produce chemokines and suppress HIV replication in vitro.

The innate immune system may be critical in the prevention of perinatal HIV infection. Since neonates have limited immunological experience, they may rely more on the ability of the innate immune system to defend against infection than their adult counterparts. To assess the potential of human neonatal natural killer (nNK) cells to suppress HIV infection in a noncytolytic manner, we evaluated their ability to secrete chemokines and inhibit HIV replication in vitro. nNK cells were cocultured with autologous, HIV-infected CD4(+) T cells and their suppressive activity against HIV was compared to nCD8(+) T cells and adult NK cells. We found that nNK cells could suppress HIV replication in autologous CD4(+) T cells infected with a CCR5-utilizing virus, but were unable to suppress replication by a CXCR4-utilizing virus. nNK cell-mediated suppression of HIV replication was comparable to that of nCD8(+) T cells and greater than that of NK cells from adults. Suppression was mediated by soluble factors, and was abrogated by the addition of an excess of anti-CC-chemokine Ab directed at CCR5 ligand chemokines. In contrast, inhibition of HIV replication by autologous nCD8(+) T cells was not fully abrogated with anti-CC-chemokine Abs indicating, as previously reported in HIV-infected adults, that other factors in addition to chemokines play a role in CD8(+) T cell-mediated suppression of HIV replication. Our results show that nNK cells can inhibit HIV replication via a chemokine-mediated mechanism, and support a potential role for the innate immune system in preventing perinatal transmission of HIV in a noncytolytic manner.

Adult↗
PubMed2003

Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks.

The genetic programs underlying neural stem cell (NSC) proliferation and pluripotentiality have only been partially elucidated. We compared the gene expression profile of proliferating neural stem cell cultures (NS) with cultures differentiated for 24 h (DC) to identify functionally coordinated alterations in gene expression associated with neural progenitor proliferation. The majority of differentially expressed genes (65%) were upregulated in NS relative to DC. Microarray analysis of this in vitro system was followed by high throughput screening in situ hybridization to identify genes enriched in the germinal neuroepithelium, so as to distinguish those expressed in neural progenitors from those expressed in more differentiated cells in vivo. NS cultures were characterized by the coordinate upregulation of genes involved in cell cycle progression, DNA synthesis, and metabolism, not simply related to general features of cell proliferation, since many of the genes identified were highly enriched in the CNS ventricular zones and not widely expressed in other proliferating tissues. Components of specific metabolic and signal transduction pathways, and several transcription factors, including Sox3, FoxM1, and PTTG1, were also enriched in neural progenitor cultures. We propose a putative network of gene expression linking cell cycle control to cell fate pathways, providing a framework for further investigations of neural stem cell proliferation and differentiation.

Animals↗
PubMed2003

HIV envelope induces virus expression from resting CD4+ T cells isolated from HIV-infected individuals in the absence of markers of cellular activation or apoptosis.

Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir.

Apoptosis↗
PubMed2003

Classical Hodgkin lymphoma is associated with frequent gains of 17q.

The etiology of Hodgkin lymphoma (HL) is poorly understood, and studies of the genetics of this disease have been hampered by the scarcity of the Hodgkin and Reed-Sternberg (HRS) cells within tumors. To determine whether recurrent genomic imbalances are a feature of HL, CD30-positive HRS cells were laser-microdissected from 20 classical Hodgkin lymphomas (cHLs) and four HL-derived cells lines and subjected to analyses by comparative genomic hybridization. In primary tumors, the most frequently involved chromosomal gains were 17q (70%), 2p (40%), 12q (40%), 17p (40%), 22q (35%), 9p (30%), 14q (30%), and 16p (30%), with minimal overlapping regions at 17q21, 2p23-13, 12q24, 17p13, 22q13, 9p24-23, 14q32, 16p13.3, and 16p11.2. The most frequent losses involved 13q (35%), 6q (30%), 11q (25%), and 4q (25%), with corresponding minimal overlapping regions at 13q21, 6q22, 11q22, and 4q32. Statistical analysis revealed significantly more gains of 2p and 14q in the older adult cases; loss of 13q was associated with a poor outcome. The results suggest that there is a set of recurrent chromosomal abnormalities associated with cHL and provide further evidence that cHL is genetically distinct from nodular lymphocyte predominance Hodgkin lymphoma (NLPHL). Abnormalities of 17q are infrequent in other lymphomas or NLPHL; this finding, coupled with current knowledge of gene expression in cHL, suggests that genes present on 17q may play an important role in the pathogenesis of cHL.

Adolescent↗
PubMed2003

Productive HIV infection of resting CD4+ T cells: role of lymphoid tissue microenvironment and effect of immunomodulating agents.

The ability of resting CD4+ T cells to support HIV replication is relevant to understanding how the reservoir of HIV-1-infected resting CD4+ T cells is generated, maintained and, hopefully, how it might be reduced or eliminated. We have utilized a tonsillar histoculture system to demonstrate that HIV, particularly X4 strains, can productively infect phenotypically resting CD4+ T cells in vitro and that this event is largely dependent on the lymphoid tissue microenvironment. Highly purified CD4+ tonsillar T cells that lack expression of both cell surface and nuclear antigens characteristic of classic T cell activation produce X4 HIV-1 mRNA, p24, and infectious virus while maintaining a resting phenotype when cultured in a tonsillar tissue microenvironment; in contrast, comparable purified resting CD4+ tonsillar T cells that have been exposed to X4 HIV do not support HIV replication when cultured in the absence of a lymphoid tissue microenvironment. HIV production from phenotypically resting CD4+ T cells is dramatically inhibited by anti-proinflammatory cytokine agents or immunosuppressive cytokines, but is only modestly suppressed by an inhibitor of the cell cycle. The ability of resting CD4+ T cells to support HIV replication in the microenvironment of the lymphoid tissue has implications in the pathogenesis of HIV disease and may provide an additional avenue for therapeutic intervention.

Adult↗
PubMed2003

A no-name tuberculosis tracking system.

Foreign-born persons from countries where tuberculosis (TB) is endemic make up a significant percentage of poultry industry workers in Delaware, a leading poultry-producing state. Many of these workers enter the United States without documentation and assume multiple identities, making it difficult for public health staff to investigate TB contacts who work in the poultry plants. The Sussex County Health Unit of the Delaware Division of Public Health developed a no-name TB tracking system to facilitate identification and treatment of poultry plant workers with TB infection and disease in a high-risk population whose members assume one or more aliases. Completion rates for treatment of latent TB infection in this group increased from 48% to 64% 2 years after the program's implementation.

Agricultural Workers' Diseases↗
PubMed2002

Response to thalidomide in chemotherapy-resistant mantle cell lymphoma: a case report.

Mantle cell lymphoma is an aggressive B-cell lymphoma with a poor median survival despite conventional therapy. Here, we present the case of a patient with multiply relapsed mantle cell lymphoma, having failed treatment with chemotherapy, steroids and rituximab. He was treated with single-agent thalidomide at a dose of 800 mg daily and entered a good partial remission which was maintained for the next 6 months. There is clearly a need for further studies of thalidomide in mantle cell lymphoma to confirm this promising initial result.

Aged↗
PubMed2002

Successful infliximab treatment for steroid-refractory celiac disease: a case report.

Celiac disease is a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. The majority of patients responds to a gluten-free diet but a small number do not. After the exclusion of gluten in the diet, ulcerative jejunititis, and an enteropathy-associated T-cell lymphoma, another treatment modalities, such as systemic steroids and immunosuppressives, may be necessary. This article reports the case of a 47-year-old white woman with immunoglobulin A deficiency. She was diagnosed with celiac disease with subtotal villous atrophy on jejunal biopsy together with positive antiendomysium and antigliadin immunoglobulin G antibodies. Despite close adherence to a gluten-free diet, her weight continued to decrease, she had diarrhea, and her distal duodenal histology showed no improvement. Some improvement in her symptoms was observed with cyclosporine and systemic steroids, but this was not sustained. Recent evidence has suggested that anti-tumor necrosis factor alpha antibodies have a role in the amelioration of an animal model of villous atrophy, and after careful consideration, she was treated with infliximab. There was a dramatic improvement in her weight, symptoms, and distal duodenal histology. The response has been maintained for 18 months while on azathioprine therapy. It is concluded that infliximab is an effective treatment that may be considered in a small number of patients with refractory celiac disease, resistant to other therapy.

Antibodies, Monoclonal↗