The enemy of science is within.
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Attitude↗
Biomedical subjects
C H Fox
Publications and source records attributed to C H Fox.
The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.
The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary.
Adrenal Cortex↗
Antiretroviral monotherapy in early stage human immunodeficiency virus disease has no detectable effect on virus load in peripheral blood and lymph nodes.
Initiation of antiretroviral monotherapy early in the course of infection with human immunodeficiency virus may result in a temporary slowing in the rate of disease progression; however, little is known about the virologic effects of early therapy. Virus load was measured in peripheral blood and lymph nodes from 16 antiretroviral-naive patients with a mean CD4 T lymphocyte count of 659 cells/microliter at baseline and after 8 weeks of either no treatment or zidovudine therapy. CD4 T lymphocyte counts and all virologic parameters examined remained unchanged regardless of zidovudine treatment status. Histopathology and virus distribution within lymph nodes remained constant between baseline and week 8 in each patient, indicating that the virologic and histologic parameters examined in a single lymph node are representative of a systemic process. Early antiretroviral monotherapy with zidovudine had no effect on virologic parameters in this group of patients with relatively high CD4 T lymphocyte counts and low measures of virus load at baseline.
Adult↗
Dynamics of virus versus host interaction in children with human immunodeficiency virus type 1 infection.
To investigate the dynamic interplay between human immunodeficiency virus type I (HIV-1) replication and the extent of immune destruction in HIV-1-infected children, virus burden in lymphoid tissues (LN) and peripheral blood was compared with changes in LN architecture and cytokine levels constitutively expressed in LN. In agreement with results of a preliminary study, the plasma HIV-1 RNA level correlated with the amount of provirus in LN. However, the level was also associated with a degree of destruction of lymphoid follicular architecture and an alteration of immune cytokine expression. Expression of interleukin (IL)-4 was higher in LN with higher virus replication. Reduction of plasma viremia was associated with an increase in IL-2 mRNA levels in LN. These findings suggest that measurable virus burden in the peripheral blood is not a simple reflection of viral replication in LN but is also influenced by the extent of progressive immune destruction.
Child↗
The pathogenesis of HIV disease.
HIV disease is caused by human adapted Lentiviruses, a family of mammalian retroviruses that use the immune systems of their hosts to persist and, as their name implies (lenti = slow), to produce a disease state over long periods of time. The pathogenesis of HIV infections is now known in enough detail to make decisions about intervening in the course of the disease.
Adult↗
Cost effectiveness of periodontal services.
This paper presents the combined use of decision trees and cost-effectiveness analysis to determine on which patients new diagnostic tests can be useful, and whether they can change the dentist's decision to provide different services and thus improve patient outcomes in 5 different categories of patients. A decision tree is constructed in which the primary decision branches are "test" and "no test". The treatment and outcome branches in the test branch are affected by the results of the test which is then either negative or positive. In contrast, the treatment and outcome branches in the no-test branch represent pathways for patient therapy when the new (or additional) test is not used. Results show that even with excellent test efficacy parameters (sensitivity 0.87 and specificity 0.84) it is not cost effective to use a diagnostic test in the general population or for adults under age 45 years. However for adults > 45 years, patients referred to a periodontist, and patients with a history of periodontal disease, the test would change treatment decisions and improve patient care outcomes.
Adult↗
PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease.
PCR-in situ hybridization (PCR-ISH) was developed and utilized to determine the distribution of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes (PBL) from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). PCR-ISH of HTLV-1 tax DNA in PBL from patients with HAM/TSP revealed that 1 in 5,000 to 1 in 10,000 PBL contained virus. PCR-ISH was sensitive, because a positive signal was consistently demonstrated from the HTLV-1-infected cell lines HUT-102 (which contains four to six copies of HTLV-1 proviral DNA per cell) and MT-1 (which contains one to three copies of HTLV-1 proviral DNA per cell). Also, intracellular amplification by PCR-ISH significantly increased sensitivity compared with conventional ISH and was shown to be specific for HTLV-1 tax DNA. These results are in contrast to solution-phase PCR amplification in which greater than 1% of cells were estimated to be infected. The discordance between these results is discussed and may indicate that more than one copy of HTLV-1 tax proviral DNA is present in an individual PBL.
Base Sequence↗
Autoimmunity in chronic active Helicobacter hepatitis of mice. Serum antibodies and expression of heat shock protein 70 in liver.
Male A/JCr mice with naturally occurring Helicobacter hepaticus infection develop a progressive chronic active hepatitis and liver tumors, despite the presence of serum antibodies to Helicobacter proteins. A rabbit antiserum prepared against the bacterial proteins immunoreacted with hepatocytes present in liver sections from infected mice with progressive lesions. We found that sera from these mice contained IgG antibodies that reacted in immunoblots with recombinant heat shock protein 70 (DmaK from Escherichia coli) but not with heat shock protein 60 (GroEL) or heat shock protein 10 (GroES). A rabbit antibody to heat shock protein 70 reacted with H. hepaticus in tissue sections and to a H. hepaticus protein (70 kd) in Western blots. Immunohistochemistry and in situ hybridization for heat shock protein 70 revealed that individual hepatocytes and other cells expressed the protein in livers with hepatitis but not usually in normal livers. Liver tumors and preneoplastic lesions in infected mice did not usually express heat shock protein 70 except focally in a few tumors. In situ hybridization for H. hepaticus 16S rRNA showed that the bacteria was found throughout the liver associated with hepatitis but not within tumors. CD3+ T lymphocytes were found in close association with hepatic lesions. These data suggest a role for autoimmunity in progressive hepatitis and carcinogenesis in livers infected with H. hepaticus.
Adenoma, Liver Cell↗
Adult sleep apnea syndromes.
Persons with sleep apnea syndromes experience 10 or more episodes per hour of sleep during which airflow ceases for more than 10 seconds. Sleep apnea syndromes are classified as obstructive, central or mixed: obstructive when the respiratory muscles continue to contract but airflow is not obtained, central when respiratory effort is not present, and mixed when elements of both obstructive and central apnea are present. Approximately 4 percent of adult men and 2 percent of adult women are believed to have these conditions. In addition to having symptoms such as snoring, headaches, depression, decreased libido and fatigue, patients with sleep apnea are at risk for a range of severe complications secondary to recurrent hypoxia and hypercapnia during sleep. Diagnosis may require an overnight polysomnogram in addition to the history, a physical examination and a laboratory assessment. Less cumbersome diagnostic modalities are being developed. Treatment options include weight reduction, change in sleeping position, avoidance of sedatives, use of continuous positive airway pressure and surgical treatment.
Adult↗
Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization.
Autopsy specimens from 3 patients with human T-lymphotropic virus (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were examined for the presence of HTLV-I in the central nervous system (CNS). In situ hybridization using an HTLV-I tax RNA probe detected cells containing HTLV-I RNA in spinal cord and cerebellar sections. HTLV-I infected cells were located within the white matter and, in particular, within the anterior and lateral funiculi of the spinal cord. Consistent with previously described HAM/TSP pathology, there were perivascular infiltrates in these CNS specimens. Significantly, HTLV-I RNA was not localized to these infiltrates but was detected deeper within the neural tissue. Furthermore, phenotypic analysis demonstrated that at least some of the infected cells were astrocytes. While previous polymerase chain reaction studies have demonstrated the presence of proviral HTLV-I in CNS specimens, here we provide evidence for the in situ expression of HTLV-I RNA in the CNS of HAM/TSP patients.
Aged↗
Feedback of obstetrical outcomes as an educational tool.
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Family Practice↗
Quantitative analysis of mononuclear cells expressing human immunodeficiency virus type 1 RNA in esophageal mucosa.
The mucosa of the gastrointestinal tract is presumably an important reservoir for human immunodeficiency virus type 1 (HIV-1), but the level of virus-expressing cells within the mucosa of infected patients is not known. To study this issue, we identified HIV-1 mRNA-expressing (positive) mononuclear cells by in situ hybridization in specimens of esophageal mucosa from eight patients with acquired immune deficiency syndrome (AIDS) and esophageal infections. Such cells were not found in four patients with AIDS and no esophageal disease. Immunocytochemical staining revealed that the mononuclear cells expressing HIV-1 mRNA were lamina propria macrophages. The prevalence of positive cells was measured by triplicate determinations in each of three experiments using an inverse sampling technique. No significant differences in prevalence were found among patients or among experiments. The overall prevalence of HIV-1 mRNA-expressing cells in the esophageal lamina propria was 0.059 +/- 0.01%. This prevalence of cells expressing HIV-1 mRNA in the mucosa of patients with mucosal infections may reflect the local abundance of stimuli such as bacterial endotoxin and certain cytokines capable of inducing viral transcription.
Acquired Immunodeficiency Syndrome↗
HIV in infected lymph nodes.
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HIV Infections↗
If it ain't fixed, don't break it....
Value-judgements about the need for more 'goal-directed' or 'basic' scientific research beg the question of how the publicly funded scientific enterprise works. An efficient management would start to put things right.
Public Policy↗
In situ PCR for the detection of HTLV-I in HAM/TSP patients.
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DNA, Viral↗
The emerging field of oral pharmaceuticals.
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Anti-Bacterial Agents↗
Periodontal disease among New England elders.
Much of the existing oral epidemiologic literature is limited by having inadequate numbers of the oldest-old in their sample, having used rudimentary periodontal measures, or not having examined probability samples of community-dwelling elders. The New England Elders Dental Study (NEEDS) is the first study that documents the periodontal disease status of a probability sample of 554 adults aged 70 to 96 living within an entire U.S. Public Health Service region. The NEEDS study revealed substantially higher estimates of periodontal destruction among older adults than previous national studies would suggest. These results are consistent with several papers in the literature that suggest that periodontal disease rates are on the increase in older adults. In the coming decades dentistry should be prepared to meet the increasing need and demand for periodontal services in the growing older population.
Aged↗
In situ hybridization in HIV research.
In situ hybridization (ISH) for HIV is an arduous, demanding means of detecting viral genetic material in cells and tissues. Good ISH requires broad technical skills and devotion to controls for every step of the process as well as a critical eye when interpreting results. ISH may be used to detect HIV in three ways: by hybridizing to viral RNA, by hybridizing to proviral mRNA being produced for virion packaging, and by hybridizing to proviral DNA in the cytoplasm or integrated in the nucleus of an infected cell. Here we discuss the technical considerations involved and the problems encountered in using ISH to study the pathobiology of HIV infection.
DNA Probes↗