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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 757 records · Page 42Linked to original sources
PubMed1992

Corneal wound healing after excimer laser ablation. Effects of nitrogen gas blower.

PURPOSE: To examine the effects of blowing nitrogen gas over the cornea during photorefractive keratectomy. METHODS: Excimer laser ablations for myopia were performed on rabbit corneas with or without the blowing of nitrogen across the surface of the cornea. All eyes underwent a 5-diopter myopic ablation; in 8 eyes, a ring was used to blow nitrogen gas across the cornea, and, in 8 eyes, the same ring was used, but no nitrogen gas was blown. RESULTS: Epithelial healing occurred more rapidly in the eyes that were not treated with the gas (3.8 +/- 1.3 days) than in the gas-treated group (6.1 +/- 0.8 days; P = 0.0025). Corneal haze was greater in the group treated with gas. Results of histologic examination showed the ablated area to have a smoother surface when nitrogen was not blown across the cornea surface. CONCLUSION: Superficial corneal deturgescence produced by the nitrogen gas appears to result in a rougher surface immediately postoperatively with undesirable effects on surface healing, but further studies will be necessary to determine the applicability of these results to humans.

Animals↗
PubMed1992

Comparative genome mapping of Sorghum and maize.

Linkage relationships were determined among 85 maize low copy number nuclear DNA probes and seven isozyme loci in an F2 population derived from a cross of Sorghum bicolor ssp. bicolor x S. bicolor ssp. arundinaceum. Thirteen linkage groups were defined, three more than the 10 chromosomes of sorghum. Use of maize DNA probes to produce the sorghum linkage map allowed us to make several inferences concerning processes involved in the evolutionary divergence of the maize and sorghum genomes. The results show that many linkage groups are conserved between these two genomes and that the amount of recombination in these conserved linkage groups is roughly equivalent in maize and sorghum. Estimates of the proportions of duplicated loci suggest that a larger proportion of the loci are duplicated in the maize genome than in the sorghum genome. This result concurs with a prior estimate that the nuclear DNA content of maize is three to four times greater than that of sorghum. The pattern of conserved linkages between maize and sorghum is such that most sorghum linkage groups are composed of loci that map to two maize chromosomes. This pattern is consistent with the hypothesized ancient polyploid origin of maize and sorghum. There are nine cases in which locus order within shared linkage groups is inverted in sorghum relative to maize. These may have arisen from either inversions or intrachromosomal translocations. We found no evidence for large interchromosomal translocations. Overall, the data suggest that the primary processes involved in divergence of the maize and sorghum genomes were duplications (either by polyploidy or segmental duplication) and inversions or intrachromosomal translocations.

Chromosome Mapping↗
PubMed1992

Toxicity of a new dosage format, cisplatin incorporated in lactic acid oligomer microspheres, in mice.

A new drug delivery system, cisplatin incorporated into lactic acid oligomer microspheres (CDDP-MS), was developed for the treatment of peritoneal carcinomatoses. We studied the acute toxicity and pathological effects of CDDP-MS injected intraperitoneally in mice. The 50% lethal dose was 23.8 mg/kg (21.3-26.7 mg/kg at 95% level of confidence), which was 1.76 times that of the cisplatin aqueous solution of 13.5 mg/kg (11.9-15.3 mg/kg at 95% level of confidence). The duration for the restoration of the body weight loss was prolonged when CDDP-MS at doses close to the 50% lethal dose was administered, as compared with the cisplatin aqueous solution at doses close to its 50% lethal dose. On autopsy there were no macroscopic or microscopic differences between the two dosage forms.

Animals↗
PubMed1992

Corneal topographic changes over time after radial keratotomy.

Radial keratotomy flattens the cornea, but in a nonuniform fashion. We used computer-assisted topographic analysis to examine curvature changes in different regions of the cornea. Within 45 days after surgery in human eyes, the central and midperipheral cornea flattens and the periphery steepens. Shortly after surgery, the central cornea (within 1-1.5 mm of the corneal light reflex) is steeper than the adjacent midperipheral cornea (1.5-3 mm peripheral to the light reflex). With time, however, the central cornea flattens more than the midperiphery, such that it is no longer relatively steeper. This regional variability in corneal curvature after radial keratotomy helps explain phenomena such as multifocal lens effect after radial keratotomy, and the changes with time account for the conflicting results observed clinically in human corneas and experimentally in human eye bank eyes.

Adult↗
PubMed1992

Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets.

Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism(s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6 +/- 0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n = 3) or as microencapsulated islet allografts (n = 7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose failing from 304 +/- 117 to 116 +/- 72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6 +/- 0.4 to 2.6 +/- 0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63-172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.

Animals↗
PubMed1992

Detection of minimal residual disease by polymerase chain reaction of bcr/abl transcripts in chronic myelogenous leukaemia following allogeneic bone marrow transplantation.

The prognostic significance of detecting minimal residual disease by polymerase chain reaction (PCR) amplification of bcr/abl mRNA transcripts was investigated in 27 bone marrow samples from 20 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukaemia (CML) in complete cytogenetic remission following allogeneic bone marrow transplantation. Sixteen were transplanted in first chronic phase, two were in second chronic phase, one was in accelerated phase and one was in blast crisis. All 20 achieved complete cytogenetic remission post transplant and 15 patients had detectable bcr/abl mRNA by PCR from 2 to 22 months following the procedure. One of these patients had graft failure and one died from graft-versus-host-disease at 7 months. Of the remaining 13 PCR-positive patients, only one (8%) relapsed after 23 months; the other 12 were alive and still in remission after a median follow-up of 16+ months (ranging 5+ to 29+ months). Five patients were PCR negative; all are alive in complete clinical and cytogenetic remission at 10+, 11+, 19+, 25+ and 25+ months post transplant. In this study, detection of subclinical Ph1-positive cells by PCR was not associated with imminent clinical or cytogenetic relapse. Since late recurrence may potentially occur, long-term follow-up is required to definitely determine the prognostic value of the PCR assay.

Adult↗
PubMed1992

A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia.

The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate-dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.

Adolescent↗
PubMed1992

Predictors of infection in chronic lymphocytic leukaemia (CLL).

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001).

Aged↗
PubMed1992

Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats.

Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.

Acute Disease↗
PubMed1992

Etoposide microcrystals suspended in oil: a new dosage form to peritoneal carcinomatosis in mice.

Etoposide microcrystals suspended in oil (ETOP-OIL) were examined for their therapeutic effects on peritoneal carcinomatosis in mice. Two days after intraperitoneal inoculation with 10(5) P388 leukemia cells/mouse to CDF1 male mice, etoposide at 10-80 mg/kg was administered intraperitoneally in bolus in the form of ETOP-OIL or in the aqueous solution form. In every dose, the survival curve of the mice given ETOP-OIL was statistically significantly improved in spite of its small lethal toxicity, as compared with those given the identical dose of etoposide aqueous solution.

Animals↗
PubMed1992

Use of the speed accuracy trade-off to characterize information processing in schizophrenics and normals.

Subjects performed a signal discrimination task under four conditions: normal pace, accuracy, speed, and SATO (equal effort to speed and accuracy). Characteristically, schizophrenics demonstrated decreased accuracy, poorer compliance, increased total response time, and increased simple reaction time. Surprisingly, central processing time (decision time) was equivalent. Analysis of processing resource allocation identified significant group differences only under the SATO condition. Here, controls balanced attentional resources but patients worked almost exclusively for speed. Under conjoint performance conditions, patients apparently minimize categorical processing time at the expense of accuracy. These data are interesting as they identify specific circumstances under which schizophrenics manifest an attentional deficit.

Adult↗
PubMed1992

Mast cell-mediated inhibition of reverse cholesterol transport.

Net cholesterol efflux from cholesterol-loaded macrophages, i.e., foam cells, was induced by incubating the foam cells with high density lipoprotein3 (HDL3). However, when the incubation system included rat serosal mast cells stimulated to trigger exocytosis of their cytoplasmic secretory granules, the ability of HDL3 to induce cholesterol efflux was largely lost. This loss was found to be due to the proteolytic action of chymase, the neutral protease of the granules, which degraded the apolipoproteins of HDL3, so rendering them unable to mediate cholesterol efflux from the foam cells. The observation defines a novel cell-dependent mechanism that blocks the initial steps of reverse cholesterol transport and suggests a role for mast cell chymase in cellular accumulation of cholesterol, an early stage in atherogenesis.

Animals↗
PubMed1992

Epidermal growth factor receptor monoclonal antibodies inhibit the growth of lung cancer cell lines.

The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.

Animals↗
PubMed1992

Opportunistic intraocular infections in AIDS.

In conclusion, this clinicopathologic study has shown that CMV ocular infection is present in about 16% of terminal AIDS patients. The treatment of CMV retinitis reduces the number of CMV-infected nonocular organs and may also lessen the severity and control the spread of concurrent nonocular infection, both of which may prolong survival in AIDS patients. Other opportunistic infections, involving primarily the choroid, were also seen in a number of patients, some of whom had concurrent intraocular infections with CMV and P carinii, M avium-intracellulare, C neoformans. In addition, all of these choroidal infections were components of disseminated infection, underscoring the increasingly important role of the ophthalmologist in the diagnosis and treatment of disseminated opportunistic infections in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1992

Lymph nodal vital staining with newer carbon particle suspensions compared with India ink: experimental and clinical observations.

CH40 and CH1500AA are newly prepared carbon suspensions which were examined as vital staining dyes for their usefulness in visualizing lymphatics at operation and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of body weight and India ink were injected subcutaneously into the footpad of the right hindpaw. Regional lymph nodes were visualized and were examined stereomicroscopically to determine how intensely these nodes blackened with carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous injection). As analyzed by centrifugal particle size distribution, CH40 and CH1500AA are narrowly distributed with a small particle size (150 and 167 nm, respectively, in mean diameter). By contrast, India ink is comprised of widely distributed and relatively large particles in suspension (mean diameter--254 nm). In 10 patients undergoing radical gastrectomy for treatment of stomach cancer, CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of those nodes without metastases (387 of 512).

Animals↗