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Biomedical subjects

L Chin

Publications and source records attributed to L Chin.

At least 73 records · Page 4Linked to original sources
PubMed1992

Characterization of immortal cystic fibrosis tracheobronchial gland epithelial cells.

Tracheobronchial glands were isolated and cultured from a patient with cystic fibrosis (CF). Cultured epithelial cells were transformed with pSVori-. All transformed cell lines express cytokeratin filaments and at early passages express the junctional complex molecule cell CAM 120/80, indicating their epithelial origin. Several gland cell lines express antigens that localize to secretory cells in vivo. Cl- transport measured by 36Cl efflux shows that CF gland epithelial cells, like CF surface airway and nasal polyp epithelial cells, are unable to respond to increases in intracellular cAMP. However, they do produce an increase in intracellular cAMP after treatment with isoproterenol or forskolin. One CF gland cell line shows increased intracellular calcium in response to a number of agents and increased Cl- efflux comparable to that observed in a non-CF airway surface epithelial cell line after addition of calcium ionophore. All cell lines express CF transmembrane conductance regulator mRNA, as measured by PCR amplification of first-strand cDNA. The CF tracheobronchial gland cell lines described here are compound heterozygotes, having a single copy of the delta F508 mutation.

Base Sequence↗
PubMed1992

Magnetic resonance imaging and pathological correlates of meningiomas.

We examined the relationships between specific magnetic resonance imaging features and certain gross and microscopic characteristics of meningiomas, including vascularity, gross texture (consistency), and venous sinus involvement. Magnetic resonance imaging scans, surgery reports, and the histopathological findings of tumors were examined retrospectively in 54 patients. Sinus involvement was accurately predicted on T1-weighted images in 9 of 10 cases (P = 0.001) and tumors with cystic changes in 3 of 3 cases. T1-weighted images were not useful for predicting vascularity unless actual flow voids could be visualized (five of six cases). There was no correlation between T1 signal intensity, tumor consistency, or histological findings. In tumors without detectable vascularity on T1-weighted images, hyperintensity relative to gray matter on T2-weighted images was correlated with increased vascularity (P = 0.004). Tumors with soft consistency (P = 0.007), cellular atypia, invasion, angioblastic, or melanocytic components were also hyperintense, compared with gray matter on T2-weighted images (P = 0.0266). Aggressive meningiomas were found to be more vascular (P = 0.045). No correlation was found between the degree of surrounding edema or contrast enhancement with histopathological findings, vascularity, or consistency.

Brain↗
PubMed1991

Chloride ion transport in transformed normal and cystic fibrosis epithelial cells.

The inability of beta-adrenergic agonists (eg. isoproterenol) to activate a specific apical membrane chloride channel in epithelial cells is characteristic of cystic fibrosis (CF). The study of these channels has been facilitated by the transformation of human airway epithelial cells. Clonal populations of SV40 large T-antigen transformed airway epithelial cells from both normal and cystic fibrosis individuals have been established. A limitation in the use of these cell lines has been the loss of the ability to form tight junctions after multiple subcultures. In particular, this loss appears to be associated with cell "crisis". A selection protocol that involves growing cells in medium that is high in Ca2+ and supplemented with fetal bovine serum (FBS) has been employed to facilitate progression through crisis. One cell line (1HAEo-) that has a normal phenotype and retains tight junctions post-crisis has been produced using this protocol. Immunofluorescent staining with a monoclonal antibody to the E-cadherin adhesion molecule shows a characteristic pericellular localization, indicating the presence of the junctional complex. The presence of tight junctions has been confirmed by electron microscopy. These cells produce elevated (greater than 30 fold) levels of cAMP in response to exposure to isoproterenol or forskolin. Chloride ion transport, as measured by 36Cl- efflux, is stimulated greater than 2 fold by these agents. Three post-crisis CF cell lines which grow in serum-containing medium have been established. These do not exhibit tight junctions. Elevated (greater than 25 fold) levels of cAMP are detected in these cells after addition of isoproterenol or forskolin, but this increase in cAMP is not accompanied by an increase in 36Cl-efflux. Both normal (1HAEo-) and CF cells show increased 36Cl-efflux following addition of the calcium ionophore A23187. (ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗
PubMed1990

Response of mouse tissues to neutron and gamma radiation: protection by WR-3689 and WR-77913.

The response of mouse intestine to d(22 MeV) + Be neutrons, p(50.5 MeV) + Be neutrons, or 137Cs gamma-rays was examined using intestinal crypt-cell survival as an endpoint. The RBEs for 50.5 MeV neutrons relative to 137Cs-gamma-rays of response levels of 5 and 50 surviving cells/circumference were 1.80 and 1.86. For d(22 MeV) + Be neutrons, the RBEs at comparable cell survivals were 1.86 and 1.93. For LD50/7 day (gastrointestinal syndrome), the RBE for 50.5 MeV neutrons was 1.56 and for LD50/30 (bone marrow syndrome), the RBE was 1.29. The ability of the phosphorothioates WR-3689 [S-2-(3-methylamino-propylamino) ethylphosphorothioic acid, 450 mg/kg] and WR-77913 [S-2-(3-amino-2-hydroxypropyl) phosphorothioic acid, 800 mg/kg] to protect against p(50.5 MeV) + Be neutrons and gamma-rays also was examined in mice using lethality at seven or 30 days as the endpoints. Results were compared to previous studies with d(22 MeV) + Be neutrons WR-2721 (400 mg/kg), an appropriate comparison given the similar RBEs of the two neutron sources relative to gamma-rays. WR-77913 is a less effective protector than is WR-2721 while in some cases WR-3689 is as effective as WR-2721. The neutron DMFs for LD50/7 were 1.12 for WR-3689 and 0.99 for WR-77913. For the bone marrow syndrome (LD50/30) the neutron DMFs were 1.47 for WR-3689 and 1.21 for WR-77913. For a given type of radiation, WR-3689 is more effective than WR-77913. Both phosphorothioates protect less well against neutron radiation than against photons, as was reported previously for WR-2721.(ABSTRACT TRUNCATED AT 250 WORDS)

Amifostine↗
PubMed1990

Renal insufficiency after total body irradiation for pediatric bone marrow transplantation.

Between 1980 and 1987, 59 children with acute lymphoblastic leukemia (ALL) or stage IV neuroblastoma (NB) underwent allogeneic or autologous bone marrow transplantation (BMT). Thirty-nine of these patients were alive and in remission 6 months post BMT and were evaluable for this analysis. Sixteen have developed renal dysfunction. Eight were transplanted for relapsed ALL and received an autologous transplant. Preparation included tenopiside (VM 26), cytosine arabinoside, and cyclophosphamide followed by total body irradiation (TBI). One patient received 850 cGy in a single fraction, while all other patients received fractionated TBI (1200-1400 cGy in 6-8 fractions over 3-4 days). Eight of 11 evaluable patients who received a BMT for NB have developed late renal problems (4-7 months after BMT). The preparation for neuroblastoma patients included VM 26, cis-platinum, melphalan, cyclophosphamide and fractionated TBI (1200-1296 cGy). All 8 neuroblastoma patients had received cis-platinum as induction treatment prior to transplantation. All patients presented with anemia, hematuria and elevations of BUN and creatinine. Renal biopsies were consistent with radiation nephropathy. In conclusion, a high incidence of renal dysfunction has occurred after BMT in children with neuroblastoma and ALL. The clinical and laboratory features are consistent with either radiation nephropathy or hemolytic-uremic syndrome. The relatively young age of these patients and conditioning with intensive multi-agent chemotherapy may decrease the tolerance of the kidney to radiation injury.

Age Factors↗
PubMed1990

Randomized double-blind cross-over study of Sinemet-controlled release (CR4 50/200) versus Sinemet 25/100 in Parkinson's disease.

Sinemet-controlled release (CR4) consisting of 50 mg carbidopa/200 mg levodopa was compared with Sinemet 25/100 in 24 Parkinson's disease (PD) patients during a 16-week double-blind cross-over study. The mean age of the patients was 66.2 years, their mean duration of PD was 9.3 years. All of the patients had response fluctuations consisting mainly of the 'wearing-off' phenomenon. Some of the patients also experienced the 'on-off' phenomenon. All patients were evaluated using the unified Parkinson disease rating scale. The following significant differences were noted on Sinemet CR4. More patients noted a decrease in dyskinesias and response fluctuations; more patients experienced a decrease in stage when 'on'; more patients were 'on' longer during the day, and more patients were globally improved. The mean number of doses per day were significantly less on Sinemet CR4 (mean 5.0, range 3-8) than on Sinemet 25/100 (mean 6.2, range 4-11 doses/day). The mean dose of levodopa in Sinemet CR4 was 1,186 +/- 458 mg and the mean dose of carbidopa was 797 +/- 115 mg. The mean dose of levodopa in Sinemet 25/100 was 873 +/- 304 mg and the mean dose of carbidopa was 218 +/- 76 mg. This study indicates that Sinemet CR4 is a useful addition for patients with response fluctuations.

Aged↗
PubMed1990

Characteristics of the binding of labeled fluoromisonidazole in cells in vitro.

Radiolabeled fluoromisonidazole (FMISO) is being investigated as an imaging agent for hypoxia in tumors and nonmalignant tissues in myocardial infarct or stroke. In this study in vitro cell cultures were used to characterize the oxygen dependency of FMISO uptake and to examine other modifying factors. The uptake of [3H]FMISO was measured in four cell lines in vitro: V-79, EMT-6(UW), RIF-1, and CaOs-1. The modifying effects of different O2 levels as well as cell growth state and concentration of glucose and nonprotein sulfhydryls were examined. In these cell types an O2 level between 720 and 2300 ppm inhibited FMISO binding by 50%, relative to binding under anoxic conditions. These values bracket the O2 level which confers full radiobiologic hypoxia, about 1000 ppm. Some bound label was released from cells in the first 1 to 3 h after a 3-h anoxic labeling with [3H]FMISO, but this does not represent tritium loss from the parent molecule. Cells from unfed plateau-phase cultures took up less [3H]FMISO than did exponentially growing cells incubated at comparable O2 levels. Reducing glucose to 1/10 or 1/100 of the usual concentration in medium had little effect on binding of micromolar levels of FMISO, except in V-79 cells, where reduced glucose levels were associated with increased FMISO accumulation. Adding cysteamine to the culture medium moderately increased FMISO uptake. We conclude that cell growth state, glucose, and nonprotein sulfhydryl concentrations affect FMISO binding, albeit less than varying O2 levels: anoxic/oxic binding ratios vary from 12.6 to 28 for the four cell types examined. Nonetheless these factors must be considered in evaluating the oxygen-dependent binding of this nitroimidazole in tumors or tissues.

Animals↗
PubMed1989

Adrenal medullary transplants as a treatment for advanced Parkinson's disease.

Open autologous adrenal medullary to caudate nucleus transplantation was performed in 12 patients with advanced Parkinson's disease (PD). Ten of these patients had diurnal response fluctuations including "wearing off" and "on/off" phenomena. All of the patients were no longer satisfactorily responding to levodopa/carbidopa and dopamine agonists. The mean age of the patients was 55.1 years (range 37-65 yrs); mean duration of PD was 11.7 years (range 4-40 yrs); mean stage "on" was 3.3 (range 2-4); mean stage "off" was 4.8 (range 4-5). Mean duration of follow up from surgery was 10.4 months (range 2-17 months). Three patients improved dramatically with major changes in their lifestyle. The course of improvement in these 3 patients was different in each, implying that different mechanisms were responsible for the improvement. One of the patients died unexpectedly. In this patient, there were no surviving adrenal cells. Three patients improved moderately. Patients reported that they were "on" longer and had to take medication less often and were less dependent on individual doses of levodopa/carbidopa. The improvement has been sustained in two patients. However, in one of these patients there had to be frequent changes in scheduling to maintain the improvement. Two patients after technically successful implants did not improve. One of these patients subsequently died. In this patient there were a few surviving adrenal medullary cells. Four patients suffered major complications. One patient had a cerebral infarction and two had cerebral hemorrhages. One of these patients has shown a good recovery. One patient with autonomic insufficiency had a cardiac arrest with cerebral anoxia one week after surgery. This patient has shown a partial recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1988

MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease.

MK 458 is a potent and selective D2 receptor agonist. MK 458 consists of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in a hydroxypropyl-methylcellulose-lactose matrix. MK 458, mean dose 8.1 mg (range 2.5 to 13.5 mg), was administered to 14 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The duration of the study was 4 weeks with a titration to maximum dose in 2 weeks. The addition of MK 458 resulted in a mean reduction in levodopa of 41% (range 0 to 81%). This degree of levodopa reduction was not seen in previous studies with other DA agonists. While the reduction in signs of PD was comparable to those on levodopa, MK 458 did not induce dyskinesias or dystonias. It is postulated that MK 458 may be able to replace levodopa as the primary treatment for PD.

Adult↗
PubMed1986

Effect of naltrexone on apnea of prematurity and on plasma beta-endorphin-like immunoreactivity.

Plasma levels of beta-endorphin-like immunoreactivity (beta-ELI) were measured in premature infants with apnea (n = 11) and compared to those in nonapneic controls (n = 9). Naltrexone (1-3 mg/kg) was given to the infants with apnea, 6 of whom were also receiving methylxanthines. Chest wall movements, nasal airflow, transcutaneous PO2 and electrocardiogram were recorded for 4-6 h prior to and for 4-6 h after administration of naltrexone. Samples for beta-ELI were taken prior to and 1 h post naltrexone. beta-ELI levels were significantly higher (p less than 0.007) in infants with apnea of prematurity than in control infants. No significant difference was found in beta-ELI levels before and after naltrexone. Naltrexone did not decrease the incidence of apnea.

Apnea↗
PubMed1986

Comparison of the protective effects of three phosphorothioate radioprotectors in the RIF-1 tumor.

Three aminoalkyl phosphorothioates, WR-2721, WR-3689, and WR-77913, were compared as radioprotectors of RIF-1 tumors irradiated in vivo and assayed for cell survival in vitro. The protector doses were 50% of the acute drug LD50. The radiation dose modifying factors for the three drugs were nearly equal, ranging from 1.5 to 1.7 at surviving fractions of 0.1 and 0.05. Using biodistribution data obtained with 35S labeled drugs, the uptake in tumors was calculated as micromoles drug per gram of tumor. On this basis, tumor levels of WR-77913 were 4.5-fold those of WR-2721, and WR-3689 uptake was 2.7-fold greater than uptake of WR-2721. Thus, on a molar basis, WR-2721 appears to be the most effective protector, but all three phosphorothioates protect this tumor moderately well. In diffusible substance autoradiographs of 3H WR-3689 labeled tumors, label was generally distributed over cells with no evidence of preferential localization over nuclei.

Amifostine↗
PubMed1985

Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids.

Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled.

Animals↗
PubMed1984

Enumeration of cytoplasmic mu immunoglobulin positive acute lymphoblastic leukemia cells by flow cytometry: comparison with fluorescence microscopy.

The pre-B phenotype of childhood acute lymphoblastic leukemia, in which the mu immunoglobulin molecule is expressed in the cytoplasm of the blast cells, has been shown to have independent prognostic significance. Patients with this phenotype of the disease tend to have a poorer outcome on contemporary treatment regimens than do those with the other B-precursor phenotypes. For these clinical studies, the detection of the pre-B phenotype has depended upon fluorescent-microscope based techniques. A flow-cytometry based technique for the detection of the cytoplasmic mu immunoglobulin molecule is presented here and the results compared in detail with those of fluorescent microscopy. The results show that the two techniques are equivalent. The flow cytometry method has the advantage of a standardized control, is less labor intensive, and is observer-independent.

Cell Line↗
PubMed1983

Phonological evaluation and remediation of speech deviations of a child with a repaired cleft palate: a case study.

Phonological evaluation of the speech of a 5-year-old boy with a repaired cleft palate identified the prevalence of the following phonological patterns: singleton obstruent omission (both prevocalic and postvocalic, but particularly prevocalic voiceless); velar deviations (omissions and fronting); cluster reduction and cluster deletion; stridency deletion (omissions and stopping); liquid deviations (omissions, gliding, stopping, nasalizing, and vowelizing); and glottal replacement. The basic aspects of an individually designed facilitative remediation program based on the subject's phonological system are presented, and the results are discussed.

Child, Preschool↗