Joubert's syndrome, ocular fibrosis, and normal histidine levels.
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Biomedical subjects
Publications and source records attributed to R Johnson.
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This prospective, Human Subjects Committee and Ethics Committee approved investigation was performed to determine if coronary angioplasty (PTCA) might be a reasonable alternative revascularization method for unstable angina patients thought to be at high risk for operative (CABG) mortality. Between March 1990 and October 1991, thirty-four consecutive patients with medically refractory rest angina were deamed to have high risk of surgical mortality and underwent PTCA without surgical backup. Predicted operative mortality was calculated for each patient based upon the VA Surgical Risk Assessment model. Angioplasty of 52 vessels was attempted. Reduction in lumenal narrowing to < 50% and improved angiographic flow was obtained in 47 vessels. There were four complicating infarctions. One death occurred in the lab, and three patients with unsuccessful angioplasty died within 30 days of pump failure. Relief of angina occurred in 30/34. Thirty patients were discharged home. In follow-up from 1 to 12 months, there have been 2 late sudden deaths at 4 months and 9 months, 1 death from lung cancer; 4 patients have stable exertional angina; 2 are awaiting heart transplant but are pain free, and one patient who had PTCA during cardiogenic shock from acute myocardial infarction had elective coronary artery bypass surgery. There have been no late myocardial infarctions. The observed angioplasty 30-day mortality of 11.8% (95% confidence limit 1% to 22.6%) compares favorably with the predicted operative mortality of 23.8% for this group. This prospective but non-randomized series supports the concept that balloon angioplasty may be a reasonable alternative to surgical intervention in some patients with unstable angina and high risk for surgery. A prospective randomized trial is warranted.
A mitomycin C (MMC)- and porfiromycin (PFM)-resistant subline of the HCT 116 human colon-cancer cell line was isolated after repeated exposure of HCT 116 cells to increasing concentrations of MMC under aerobic conditions. The MMC-resistant subline (designated HCT 116-R30A) was 5 times more resistant than the parent cells to MMC and PFM under aerobic conditions. Both the MMC-resistant cells and the parent HCT 116 cells accumulated similar amounts of PFM by passive diffusion, but levels of macromolecule-bound PFM were about 50% lower in the resistant cell line, implying a decrease in PFM reductive activation in the resistant cells. The finding that microsomes from either sensitive or resistant cells showed an equal ability to reduce MMC and PFM indicated that the activity of NADPH cytochrome P-450 reductase (EC 1.6.2.4) was not changed in the resistant subline. Soluble extracts of HCT 116 cells reduced MMC and PFM more effectively at pH 6.1, and NADH and NADPH were utilized equally well as electron donors under both aerobic and anaerobic conditions. These data suggest that quinone reductase (EC 1.6.99.2; DT-diaphorase) in soluble extracts is responsible for the reduction of MMC. Quinone reductase activities in soluble extracts of HCT 116-R30A cells for the reduction of dichlorophenol indophenol (DCPIP) and menadione-cytochrome c at optimal pHs were decreased by 95% as compared with those obtained in parent cells. However, the MMC-reducing activity of HCT 116-R30A soluble extracts was only 50% lower than that of the parent cell extracts. The kinetic constants (Km, Vmax) found for quinone reductase in the two cell lines with respect to the substrates DCPIP and menadione differed. Two species of mRNA for quinone reductase (2.7 and 1.2 kb) were detected in both cell lines, and there was no detectable difference between parent and resistant cells in the steady-state level of either of these mRNA species. Furthermore, incubation with the quinone reductase inhibitor dicoumarol rendered HCT 116 cells more resistant to MMC. Alteration of the quinone reductase activity in HCT 116-R30A cells appears to be the mechanism responsible for their resistance to MMC and PFM.
We have developed an expression cassette which allows the generation of recombinant baculoviruses that can express passenger genes under the control of a constitutive cellular promoter derived from the cytoplasmic actin gene of the silkmoth Bombyx mori. Silkmoth tissue culture cells which were infected with a recombinant B. mori nuclear polyhedrosis virus (BmNPV) containing the gene-encoding chloramphenicol acetyltransferase (CAT) under the control of this expression cassette expressed significant CAT activity beginning 5 hr postinfection (p.i.). Cells infected with a recombinant BmNPV containing the cat gene under the control of the polyhedrin gene promoter did not express CAT activity until 20 hr p.i. Silkworm larvae were also infected with the two recombinant viruses by hemocelic injections and all larval tissues examined were found to express the cat gene. While significant actin-cassette-driven CAT expression in vivo was first seen at 24 hr p.i., expression from the polyhedrin promoter was not seen until 48 hr p.i. By 60 hr p.i., tissues of larvae infected with the recombinant virus expressing cat under polyhedrin promoter control were found to exhibit sixfold higher CAT activity than those infected with recombinant virus expressing the cat gene under the control of the actin promoter. The 24-hr temporal advantage in expression of a passenger gene in infected larvae indicates that the actin-promoter-based expression cassette or other analogous cellular promoter-based cassettes could be used for generating recombinant baculovirus insecticides which could incapacitate pest insects more quickly than viruses employing the polyhedrin or other late viral promoters for expressing insect-incapacitating proteins.
The accuracy of a system of intramedullary alignment using 6 mm rods was assessed in 100 patients undergoing total knee replacements. Post-operative, full length weight-bearing X-rays were used; the mechanical axis from head was used as the reference axis. The method of calculating the errors produced by flexion and rotation of the limb in relation to the X-ray beam is described, the mean deviation from the mechanical axis in 100 cases being 0.67 degrees valgus with a standard deviation of 2.47 degrees. The maximum error was 6.68 degrees valgus and 4.62 degrees varus. The purpose of this study is twofold, first to assess the accuracy of this system of intramedullary alignment and, second, to develop a method of correcting for apparent radiological misalignment using standard radiographic equipment.
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Light is a dominant mutant allele of the mouse brown locus which results in hairs pigmented only at their tips. The phenotype is due to premature melanocyte death. We have sequenced the tyrosinase-related protein-1 cDNA encoded at this locus from Light mice and found that it contains a single base alteration from wild-type, causing an Arg to Cys change in the protein. To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice. We have demonstrated premature melanocyte death, but only in pigmented mice, indicating that the cell death is mediated through the inherent cytotoxicity of pigment production.
Six cases of apparent and four cases of histopathologically confirmed vasculitis of the central nervous system (CNS), including one case of histopathologically documented vasculitis with encephalitis associated with coccidioidal meningitis (CM), are presented. Vasculitic complications included changes in mental status as well as stroke-like findings of aphasia, hemianopsia, and hemiparesis. Seven patients died. Vasculitic complications were unanticipated and often abrupt in onset, and delayed therapeutic intervention was characteristic. The diagnosis of vasculitis/encephalitis due to Coccidioides immitis infection must be based on clinical judgment, since serum antibody titers, cerebrospinal fluid findings, and initial radiological studies are not always helpful. Institution of both intravenous and intracisternal administration of amphotericin B and possibly concomitant intravenous administration of dexamethasone may be warranted in situations in which the association of C. immitis with CNS vasculitis or encephalitis appears likely before serologic or cultural confirmation of C. immitis infection involving the CNS is available.
This 1988 study reports the point and lifetime prevalence of psychiatric disorders, using DSM-III-R criteria, of a sample (approximately 25%) of adult members of an Indian village previously studied in 1969. The basic instrument was the Schedule for Affective Disorders and Schizophrenia, augmented by available medical information and administered by experienced psychiatrists. Subjects were interviewed and results were weighed for the age- and sex-distributed population. The results indicated a high point prevalence of alcohol dependence (32.8%), with a lifetime prevalence of 72.8%, among males. The lifetime prevalence of affective disorders among women was also high (36.8%), but less so among men (19.3%). When compared with the DSM-III-R diagnoses of the 1969 study, the point prevalence rates of alcohol dependence and abuse disorders fell from 39% to 21%. Also, fewer subjects were judged to be psychiatrically impaired. Even though the prevalence of psychiatric disorders was lower in the current study, the rates for alcohol disorders and affective disorders were still far higher than those reported in Epidemiologic Catchment Area studies. Alcohol dependence (especially among young men) and affective disorder (among women) were major problems.
A chicken embryo cDNA library was screened with a mouse probe for ornithine decarboxylase (ODC) and 14 positively hybridizing clones isolated. The longest of these (1.7 kb) was sub-cloned and sequenced. It is estimated that the clone comprises approximately 98% of the coding region for chicken ODC. The DNA sequence shows 78% identity with the human ODC cDNA sequence and the deduced amino acid sequence is almost 90% homologous to mouse and human. Both the peptide and cDNA sequences show interesting potential regulatory features which are discussed here.
The acquired immunodeficiency syndrome (AIDS) pandemic has highlighted the need for safeguards against the inadvertent transmission of infectious disease in the psychophysiology laboratory. These Guidelines identify factors contributing to the risk of bloodborne disease transmission to subjects or technicians, and recommend procedures to minimize such risk, given current knowledge and techniques. The lowest risk is associated with the application of devices, such as surface electrodes, to nonabraded, intact skin. Such devices should be clean, but do not require disinfection. The potential risk of infection is higher when surface electrodes are applied to non-intact skin. Abrasion, or other breaks in the skin, can allow seepage of blood products carrying such pathogens as hepatitis B virus and the human immunodeficiency virus that causes AIDS. Thus electrodes require high-level disinfection before reuse on non-intact skin. In addition, technicians should wear gloves during skin preparation and should abrade the skin no more than necessary, using only sterile, preferably non-sharp materials. The highest risk is that associated with items that enter sterile tissue, such as subdermal electrodes and the needles and lancets sometimes used in skin preparation. Such items must be sterile at the time of use and must be handled with extreme caution.
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We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm). Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients' RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms. The patients' memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes.
Cultured rat glomerular epithelial cells (GEC) were examined for their ability to release extracellular matrix-degrading proteinases with [3H]gelatin as substrate. GEC-conditioned media, under serum-free conditions, contained modest amounts of gelatinase activity (1 to 10 U/mg of protein); the activity was maximal at neutral pH, was inhibited by zinc chelators, was not inhibited by tissue inhibitor of metalloproteinase-2, and could not be further activated by trypsin or organomercurials. Gelatin substrate sodium dodecyl sulfate-polyacrylamide gels of GEC-conditioned medium revealed several zones of lysis, with molecular sizes of 150 kd (major band), and 220, 86 to 93, and 52 to 54 kd (minor bands). Northern blot analysis demonstrated that the GEC metalloproteinase(s) were distinct from the 68- to 72-kd type IV collagenase/gelatinase present in mesangial cells or the 92-kd type IV collagenase present in neutrophils. The GEC gelatinolytic activity also degraded insoluble type IV collagen in glomerular basement membrane in a dose-dependent manner. The major metalloproteinase activity responsible for the type IV collagen degradation has a molecular size of 150 kd with a type IV collagen substrate gel. Thus, GEC produce several neutral metalloproteinases, which, by virtue of their substrate specificity, may play an important role in glomerular basement membrane remodeling and in glomerular diseases characterized by alterations in basement membrane permeability.
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Ten healthy males (mean age 22.3 +/- 0.8 yr) pedaled with maximal effort for 30 s against a workload adjusted prior to the start of the test to 0.98 N.kg body mass-1. Blood samples were collected before, and 3 min and 1 h following exercise. Peak and average power mean values were 1020 +/- 51 and 738 +/- 34 W, respectively. Total leukocytes increased 40% in response to the exercise bout, but were 16% below pretest levels after 1 h of recovery (F = 123, P < 0.001). Neutrophils and lymphocytes represented approximately 60% and 30% of the leukocytosis, respectively. Lymphocytes increased 30% following exercise, but were 36% below pretest levels after 1 h recovery (F = 56.4, P < 0.001). The post-test lymphocytosis can be explained primarily from the 176% increase in natural killer cells (NK) and 28% increase in cytotoxic/suppressor T cells, while the 1-h recovery lymphopenia occurred because of a sharp decrease in total T cells and a moderate decrease in NK cells. No significant changes in lymphocyte proliferative response or serum immunoglobulin levels were found when appropriate adjustments for changes in plasma volume or lymphocyte subset changes were made. Plasma epinephrine increased 300% in response to the exercise bout, and best explains the measured changes in circulating levels of lymphocyte subsets. These results demonstrate that changes in circulating levels of leukocyte and lymphocyte subsets, especially NK cells, occur rapidly in response to 30 s of brief, heavy exertion.