Biomedical subjects
Publications and source records attributed to M Lee.
cDNA and genomic clones of Neurospora calmodulin were obtained by PCR. Characterization revealed an open reading frame encoding a predicted protein of 149 amino acids, showing 85% identity to the human calmodulin protein sequence. Comparison of the cDNA and genomic sequence reveals the position of five introns, organized differently than is found in calmodulin genes from higher eukaryotes.
GABA (gamma-aminobutyric acid) depresses axonal conduction in neonatal dorsal columns. GABA released by injured spinal neurons may diffuse to white matter and contribute to secondary axonal damage. We studied the effects of hypoxia and GABAA receptor blockade on dorsal column conduction in vitro. The experiments compared the effects of hypoxia on longitudinally hemisected spinal cords and isolated neonatal dorsal columns. Before hypoxia, electrical stimulation elicited robust conducted compound action potentials in both isolated dorsal columns and hemicords. The tissues were superfused for 120 min with a hypoxic Ringer's solution saturated with 95% N2 and 5% CO2, followed by oxygenated Ringer's solution for 90 min. Isolated dorsal columns were remarkably insensitive to hypoxia. Response amplitudes fell by only 11 +/- 7% (n = 5) during hypoxia. In hemicords, however, hypoxia reduced response amplitudes by 56 +/- 16% (n = 5, mean +/- S.E.M.) and re-oxygenation did not restore response amplitude. We applied bicucullin (10(-5) M) to block GABAA receptors in the hemicords during hypoxia. Response amplitudes in bicucullin-treated hemicords fell by only 3 +/- 9% (n = 5) during hypoxia but declined 31 +/- 5% during re-oxygenation. These results suggest that endogenous GABA released from gray matter contributes to hypoxia-induced dorsal-column conduction failure.
OBJECTIVE: To compare the effects of blowing dry (nitrogen or helium) and humidified gases over the corneal surface during photorefractive keratectomy. METHODS: Excimer laser myopic ablations were performed on porcine eyes (10 per group) using humidified and dry nitrogen and helium gas under ambient conditions. Surface smoothness was quantified with light and electron microscopy. RESULTS: Corneas that were ablated using humidified gas were smooth and equivalent to those ablated under ambient conditions. Dry nitrogen and helium blowing resulted in increased surface irregularity evident on light and electron microscopy (P < .001). The pseudomembranes in the humidified gas and ambient air groups had fewer surface discontinuities than did those in the nonhumdified gas groups and appeared to have a thinner electron-dense surface layer. CONCLUSIONS: The blowing of humidified gas during excimer laser corneal ablation produces a smoother surface than does the blowing of dry gas and is comparable to that produced under ambient (no blowing) conditions. Maintaining corneal moisture is important in photorefractive keratectomy. If blowing gas is necessary to remove debris from the surface, the gas should be humidified.
Although combination chemotherapy induces complete remission in 60-90% of adults with acute lymphoblastic leukemia, only 20-45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m2 IV qd x 5), ifosfamide (1.5 g/m2/d x 5), and mitoxantrone (8 mg/m2/d IV x 3) in 11 adult patients with relapsed or refractory ALL. The median follow-up of all patients completing therapy is 208 days (30-484+ days). Eight of 11 (73%; 95% confidence interval 45-92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50-151 days). Median time to granulocyte > .5 x 10(9)/L was 28 days (21-46 days) and the median time to platelet recovery > 20 x 10(9)/L was 24 days (21-39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL.
Improvement in cervical range of motion in patients with spasmodic torticollis by botulinum A toxin injection is difficult to objectively measure. Recently, a three-dimensional cervical range of motion system (EMROM) that measures primary as well as secondary cervical angles has been developed. This system uses an electromagnetic tracking system for data collection and a personal computer for analysis and graphic display of the data. We have tested the EMROM system and, from our results, believe that it can be used clinically to objectively and accurately measure cervical range of motion in patients who have spasmodic torticollis and who receive botulinum toxin injections.
The existing means of detecting recurrent ovarian carcinoma are notoriously poor. Positron emission tomography (PET) is a form of computer-assisted imaging which produces images reflective of the biochemistry of the tissues rather than their physical characteristics. PET imaging with the positron emitting glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) exploits the accelerated rate of glycolysis characteristic of malignant tissue to image tumors. To begin to study PET's ability to diagnose recurrent ovarian cancer, whole-body PET FDG scanning was performed on 13 patients prior to planned surgical exploration. Seven patients were suspected of having recurrence based upon clinical findings, and 6 patients were clinically free of disease. In all 6 of the patients with suspected recurrence who subsequently underwent surgery, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings. Both intraperitoneal and extraperitoneal lesions were detected by PET. All 6 patients judged clinically free of disease had negative PET scans, but in 5 of these microscopic foci of residual tumor were found at surgery. Although PET FDG cannot replace surgery in the detection of microscopic recurrence, it can accurately detect tumors greater than 1.0 cm in diameter.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A malignant tumor that arose spontaneously in the subcutaneous tissue of the back of a C57BL/6 female mouse was found to metastasize spontaneously to the liver. The primary and metastatic tumors, SML (spontaneous metastasis to the liver) 1 and SML 2, were established in vitro in long-term cell suspension culture and were passaged 10 times in vivo for 18 months. When 100,000 cells were injected subcutaneously in the orthotopic position, tumor growth appeared in 60% of the SML 1 mice and 100% of the SML 2 mice. SML 1 did not grow when injected in the footpad, while SML 2 did. The median survival was 47 days for SML 1 and 48.5 days for SML 2 (P = 0.013). The pattern of metastasis was similar for both tumor cell lines, irrespective of intravenous or subcutaneous injection routes. Spontaneous metastasis of the SML 2 line occurred from both the orthotopic and heterotopic sites, while the SML 1 metastasized spontaneously from the orthotopic site only. Liver metastasis appeared in > 90% of the mice for both SML 1 and SML 2. Metastasis to the spleen occurred in about half the mice. Other sites of metastasis were the ovaries (36% and 52%, respectively, for SML 1 and SML 2), the kidneys (approximately 15%) and the small bowel (very rarely). Metastasis to the lungs did not occur except very rarely in the later passages of the SML 2 line. Histologic, immunohistochemical and electron microscopic studies showed a histiocytic tumor with macrophage characteristics. The cells exhibited chemotaxis toward liver extracellular matrix and reduced motility toward collagen IV, laminin and fibronectin compared to the B16-F10 melanoma line. This spontaneously occurring tumor should prove useful for the study of organ-specific metastasis to the liver.
Explore the source record for details and available documents.
BACKGROUND: A new drug-delivery format comprising activated carbon particles adsorbing peplomycin (PEP-CH) was developed for the treatment of superficial esophageal cancer. METHODS: The drug distribution was measured in rats that received subcutaneous injections of PEP-CH or peplomycin aqueous solution. In 6 patients with superficial esophageal cancer, peplomycin as PEP-CH, 5-10 mg once a week for 4-10 weeks (total, 40-100 mg/patient) was injected endoscopically into primary lesions. RESULTS: Rats given PEP-CH had significantly higher peplomycin levels in the regional lymph nodes and the injection site than rats given aqueous solution. Five patients have survived to the present or died without cancer after 27-72 months. The remaining patient has survived without cancer for 8 months after a second course of PEP-CH against recurrence. CONCLUSIONS: PEP-CH therapy seems to have a good therapeutic effect on superficial esophageal cancer, although the present clinical study may have been biased by patient selection.
We investigated the mechanisms of allogeneic stimulation induced TNF-alpha production in vitro by using human peripheral blood mononuclear cells (PBMC) and Daudi lymphoblastoid B-cells. PBMC produced TNF-alpha in response to mitomycin C-treated or paraformaldehyde-fixed Daudi cells, reaching a peak level after 4-6 h of culture. Monocytes were identified as the major source of TNF-alpha produced during allogeneic cell interaction. The second potent producer of TNF-alpha was E-rosette non-forming natural killer cells. Purified T-cells did not produce significant levels of TNF-alpha, even in the presence of IL-1 and IL-6. Interleukin-4 (IL-4) down-regulated TNF-alpha production by monocytes, but in contrast interferon-gamma (IFN-gamma) moderately enhanced TNF-alpha production. Our results indicate that monocytes are mainly responsible for the production of TNF-alpha in response to allogeneic stimulation, and T-cells modulate monocyte function by their soluble factors.
We have investigated the expression of plasminogen activators (PAs) and PA inhibitors (PAIs) by an asbestos-induced mesothelioma. Using zymographic, immunological and biochemical techniques it was demonstrated that cell lines derived from the tumor express high levels of PAI and low levels of a UK-like PA. Adherent and partially non-adherent variants of the mesothelioma expressed indistinguishable amounts of PAI and UK. Based on partial biochemical characterization, the PAI secreted by the mesothelioma cells was a set of PAIs which consisted of PAI-1 in addition to other species. These observations indicate that the difference in growth phenotype of the adherent and partially non-adherent lines was not due to detectable differences in PA and PAI expression.
Explore the source record for details and available documents.
PURPOSE: This study compares the outcomes of trabeculectomy and Molteno implantation in the treatment of glaucomas associated with uveitis. METHODS: Forty-five patients with uveitis, who had undergone filtering surgery for glaucomas associated with uveitis, were reviewed retrospectively. Successful outcome was defined as final intraocular pressure (IOP) of 6 to 21 mmHg, with a minimum follow-up of 6 months without visually devastating complications or loss of light perception. RESULTS: One- and two-year life-table success rates, respectively, were 81% and 73% with trabeculectomy (16 patients); 53% and 31% with combined trabeculectomy and first-stage (reserve) Molteno implantation (19 patients); and 79% and 79% with one-stage Molteno implantation (10 patients). In 11 patients who underwent second-stage Molteno implantation after trabeculectomy failure, 1- and 2-year life-table success rates were 79% and 79%, respectively. Complications included surgically treated choroidal effusions (1/45; 2%), choroidal hemorrhages (3/45; 7%), and chronic hypotony (3/45; 7%). Follow-up in all groups ranged from 5 to 70 months (mean +/- standard deviation, 28 +/- 17 months). CONCLUSIONS: Trabeculectomy provides surprisingly good results in glaucomas associated with uveitis (modulation of wound healing with antimetabolites probably would afford an even higher success rate). However, when significant, immediate postoperative and/or moderate chronic postoperative inflammation is likely, aqueous drainage devices appear more likely to control IOP.
Explore the source record for details and available documents.
Although it is frequently stated that patients with cirrhosis are more sensitive to benzodiazepines, the relative roles of impaired elimination and altered responsiveness have not been clarified. We evaluated the pharmacokinetics, pharmacodynamics, and sensitivity to triazolam in six patients with clinically stable cirrhosis and six age-matched control subjects. Our findings show that there were no significant differences between the patients with cirrhosis and the control subjects in any of the pharmacokinetic parameters. Drug effect, measured as postural sway, was also similar in the patients with cirrhosis and control subjects; therefore the ratio of effect area under the curve to concentration area under the curve, a measure of sensitivity, did not differ significantly between the patients with cirrhosis and the control subjects. Because triazolam is metabolized by P4503A, we hypothesized that the effects of cirrhosis on drug metabolism may differ with respect to the specific P450 responsible for the oxidation of this drug. These effects may differ because of the relative sparing of a specific P450 and because of an extrahepatic site of metabolism.