PubMed HealthSearch

Biomedical subjects

L W Lee

Publications and source records attributed to L W Lee.

At least 19 recordsLinked to original sources

Population heterogeneity of higher-plant mitochondria in structure and function.

Mitochondria of rapidly developing mungbean seedlings were fractionated into four populations: two density classes, each from a 1500S and a 150S pellet. Each of the four populations exhibited cytochrome c oxidase (COX) activity and contained mitochondrial DNA and cardiolipin; plastid and glyoxysome content were found to be relatively low. Five mitochondrial membrane proteins, COXII/III, ATPase alpha/beta and porin, and a matrix enzyme, manganese superoxide dismutase (MnSOD), were detected by immunoblots in all four populations. Another matrix enzyme, pyruvate dehydrogenase was detected only in the two respiratory-competent 1500S populations. The two 150S populations contained a previously unidentified organelle that lacked demonstrable respiratory capability. This organelle, which we have tentatively referred to as "slow-sedimenting (ss-) mitochondrion", was small in size (below light-optics resolution, 70-300nm, majority < or =200nm) and possessed a peculiar looking boundary membrane, ribosomes, and an occasional prominent electron-dense spot. Characteristically, ss-mitochondria were almost always in contact with a filament-aligned membrane-like structure of varying length. Cristae structure, while undetected in small ss-mitochondria, appeared in larger individuals. Typical mitochondria were found in the denser 1500S population, while the lighter 1500S population consisted of 300-800 nm mitochondria exhibiting a varying degree of size-dependent inner membrane folding. Using electron microscopy (EM) immunolocalization and serial sectioning, we have identified in situ organelles resembling in size and in fine structure the ss-mitochondria, which also exhibit a size-dependent folding of the inner membrane. These results suggest that small ss-mitochondria may undergo a progressive development in situ. Taken together, our findings demonstrate the existence of a pattern of structure-function-coordinated gross heterogeneity among mitochondria. This pattern of mitochondrial heterogeneity, characterized both in isolated mitochondria and in situ, implies that small ss-mitochondria may represent a type of "nascent mitochondria" derived from a yet unidentified mitochondria-propagation mode operating during rapid seedling growth. Mitochondrial division by binary fission, characterized by the appearance of dumbbell-shaped intermediates, was also detected.

Cardiolipins

Effects of sorbitol dehydrogenase deficiency on nerve conduction in experimental diabetic mice.

In this report, we made use of sorbitol dehydrogenase (SDH)-deficient mutant mice (C57BL/LiA) to test whether there is a close correlation between the level of polyol accumulation and the degree of reduction in motor nerve conduction velocity (MNCV) associated with diabetes. The C57BL/LiA mouse has SDH deficiency due to a G-to-A mutation at the +1 position of intron 8, thus producing only aberrant SDH transcripts. These C57BL/LiA mice should have higher levels of polyol accumulation in the peripheral nerve because of the inability to further metabolize sorbitol to fructose. Here, we confirm by Western blot analysis and high-performance liquid chromatography that these mice lack SDH in the sciatic nerve and other various tissues, whereas normal mice possess SDH. These C57BL/LiA mice do not display any obvious phenotype that includes peripheral neuropathy in the normal laboratory environment and breed normally as described previously, although the tissues that normally contain SDH accumulate more sorbitol. This finding suggested that C57BL/LiA mouse strain is a valid model for studying the role in diabetic neuropathy of the polyol pathway, which consists of two enzymes-aldose reductase for converting glucose to sorbitol and SDH for converting sorbitol to fructose. Sorbitol levels in the sciatic nerve of diabetic C57BL/10N, nondiabetic, and diabetic C57BL/LiA mice were increased 4.3-, 16.6-, and 38.1-fold, respectively, above that of nondiabetic C57BL/10N. The fructose level in the sciatic nerve was increased 2.4-fold in diabetic C57BL/10N mice compared with that of nondiabetic and diabetic C57BL/LiA mice. Diabetic SDH-deficient mice showed an MNCV reduction similar in magnitude to that of diabetic C57BL/10N mice, despite greater nerve sorbitol accumulation and the lack of fructose in the former. The present data suggest that the levels of sorbitol and fructose in the sciatic nerve of mice do not correlate with the severity of MNCV deficit associated with diabetes.

Animals

Type-4 pili of Kingella denitrificans.

Kingella denitrificans possess type-4 pili, and the type strain, ATCC 33394, contains at least four complete copies of type-4 pilin-encoding genes. Previously reported hybridization patterns of K. denitrificans chromosomal DNA seen using a Neisseria gonorrhoeae pilin gene region probe, had been interpreted as representing possible partial, silent gene loci. This now appears to be due to cross-reaction to multiple copies of 18-bp inverted repeat structures. Data are presented on a variety of colony variants which have changed from a spreading-corroding (SC) phenotype to a nonspreading-noncorroding (N) phenotype. Interestingly, while the SC to N transition is most often associated with loss of piliation in other bacteria containing type-4 pili, many of the K. denitrificans N variants still produce pilin, and some still produce pili.

Bacterial Outer Membrane Proteins

Mechanism involved in the antiplatelet activity of naloxone in human platelets.

In this study, naloxone was tested for its antiplatelet activity in human platelet suspensions. In platelet suspensions (4.5 x 10(8)/ml), naloxone (0.1-0.5 mM) significantly inhibited platelet aggregation and ATP-release stimulated by various agonists (i.e., thrombin, collagen, U46619, and ADP). Furthermore, naloxone (0.5 and 0.8 mM) dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM loaded platelets stimulated by collagen. Additionally, naloxone (0.5 and 1.0 mM) did not influence the binding of FITC-triflavin to platelet glycoprotein (GP) IIb/IIIa complex. On the other hand, naloxone (0.5 mM) markedly decreased the fluorescence of platelet membranes tagged with diphenylhexatriene (DPH). In addition, naloxone (0.1-0.5 mM) did not significantly affect cyclic-AMP levels in human washed platelets. It is concluded that the antiplatelet activity of naloxone may possibly be due to the induction of conformational changes in the platelet membrane and the inhibition of the intracellular Ca2+ ([Ca2+]i) mobilization as well as the release reaction of platelets stimulated by agonists.

Blood Platelets

The development of the "Cantonese receptive vocabulary test' for children aged 2-6 in Hong Kong.

The study aims to develop a Cantonese receptive vocabulary test to assess 2-6-year-old children in Hong Kong. The test consists of 100 test items. Each target item is accompanied by a phonological distractor, a semantic distractor and an unrelated distractor. A sample of 609 normal children from four Maternal and Child Health Centres and nine kindergartens was selected. The results show that there is a significant effect of age on the correct score. ANOVA was performed to look at the age effect on each distractor individually. It was found that the scores of the three distractors decrease in their own patterns as age increases. With strong content validity, strong construct validity and high correlation coefficients in the split-half reliability, this test could be used as a reliable measurement for the Cantonese-speaking population in Hong Kong.

Analysis of Variance

Anterior segment prosthesis development: retinal function following anterior segment removal.

Replacement of the entire anterior segment of the eye is a very ambitious and complex endeavor and it is not known whether the retina remains functional when the anterior structures have been removed. We used routine histo-pathologic evaluation and electroretinographic measurements to determine the structural and functional status of rabbit retinas following surgical removal of the internal anterior structures (iris, ciliary body, and lens) and replacement of the vitreous with silicone oil. In some cases, we were able to record both a scotopic and a photopic electroretinographic response as long as 15 weeks after complete removal of the internal anterior segment structures. Although many hurdles remain and more efficacious surgical techniques and biomaterials need to be developed, our results suggest that, in the rabbit, the retina may continue to function in the absence of critical anterior segment structures.

Animals

Identification of four complete type 4 pilin genes in a single Kingella denitrificans genome.

We have cloned and sequenced four complete type 4 pilin genes from the type strain (ATCC 33394) of Kingella denitrificans. Two of these pilin genes, kdpB and kdpD, are in tandem, oriented in the same direction, and encode pilins of only 50% amino acid identity. The kdpA and kdpC loci are separately located from the kdpB-kdpD locus and from each other. At the DNA level kdpA and kdpC are nearly identical to kdpB and encode pilin proteins that are identical to KdpB. Bands of multiple hybridization previously hypothesized to be due to partial silent pilin gene loci are now shown to be due to the presence of 18-bp repeat sequences (IR18) associated with the pilin gene coding regions. These IR18 sequences exist most often as inverted repeats separated by 8 bp. IR18 sequences are structurally similar to the repetitive extragenic palindromic sequences of Escherichia coli, although they have different DNA sequences. The IR18 sequences also demonstrate homology to the DNA uptake sequences of Neisseria gonorrhoeae and may serve a similar function for K. denitrificans.

Amino Acid Sequence

HIV test-seeking before and after the restriction of anonymous testing in North Carolina.

OBJECTIVES: This study assessed the impact on HIV test-seeking of North Carolina's restriction of anonymous testing to 18 of its 100 counties as of September 1, 1991. METHODS: Trends from 4 months prerestriction to the 16-month restriction period in counties retaining vs counties eliminating anonymous testing were compared. RESULTS: HIV testing increased throughout the state, but more rapidly where anonymous testing was retained than elsewhere: 64% vs 44%. These differences held for all sociodemographic subgroups and were most pronounced among adolescents and African Americans and other non-Whites. CONCLUSIONS: The data are consistent with a detrimental effect of elimination of anonymous testing, although confounding from differences in AIDS awareness or in repeat tests is possible.

Adolescent

Prenatal hospitalization and compliance with guidelines for prenatal care.

OBJECTIVES: This study examined the relationship between compliance with the US Public Health Service guidelines for prenatal care and the rate of prenatal hospitalization. METHODS: For all women admitted to a Boston referral center during January and February 1993 with a pregnancy of at least 18 weeks gestation (n = 1400), a proportional hazards model was used to examine factors associated with prenatal hospitalization. RESULTS: Prenatal hospitalization occurred during 248 (17.7%) pregnancies. The median length of stay for all prenatal admissions was 4 days; the medial total charge was $5667. Prior medical and obstetrical problems were strongly associated with prenatal hospitalization. After adjustment for age, race, and medical and obstetrical complications, women who received less than 70% of the prenatal care recommended were significantly more likely to be hospitalized (relative risk [RR] = 2.14, 95% confidence interval [CI] 1.50, 3.06). CONCLUSIONS: Prenatal hospitalization is a common, costly complication of pregnancy. Because of its association with compliance with the Public Health Service guidelines for the content of prenatal care, prenatal hospitalization may be a sentinel indicator of inadequate prenatal care amenable to intervention.

Adolescent

Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS.

The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted.

AIDS-Related Opportunistic Infections

Human tissue monitoring and specimen banking: opportunities for exposure assessment, risk assessment, and epidemiologic research.

A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30 March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117 registered participants from 18 states and 5 foreign countries. The first 2 days featured 21 invited speakers from the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, various other government agencies, and universities in the United States, Canada, Germany, and Norway. The speakers provided a state-of-the-art overview of human exposure assessment techniques (especially applications of biological markers) and their relevance to human tissue specimen banking. Issues relevant to large-scale specimen banking were discussed, including program design, sample design, data collection, tissue collection, and ethical ramifications. The final group of presentations concerned practical experiences of major specimen banking and human tissue monitoring programs in the United States and Europe. The symposium addressed the utility and research opportunities afforded by specimen banking programs for future research needs in the areas of human exposure assessment, risk assessment, and environmental epidemiology. The third day of the symposium consisted of a small workshop convened to discuss and develop recommendations to the U.S. Environmental Protection Agency regarding applications and utility of large-scale specimen banking, biological monitoring, and biological markers for risk assessment activities.

Biomarkers

DNA contents and chromosomes of clonal lines of transformed rat liver epithelial cells and of cells from their derived tumors.

Clonal lines of transformed rat liver epithelial cells, derived from a single population of cloned diploid rat liver epithelial (stem-like) cell line (WB-F344) by exposure in vitro to N-methyl-N'-nitro-N- nitrosoguanidine (MNNG), produce hepatocellular carcinomas, hepatoblastomas and adenocarcinomas in syngeneic rats (Tsao and Grisham, Am. J. Pathol., 127, 168-181, 1987). In this study we show that these clonal lines demonstrate near-diploid (GN clones) or near-triploid (GP clones) aneuploidy and the universal occurrence of non-random chromosomal abnormalities. Marker chromosomes that involved four autosomes--a non-reciprocal translocation involving chromosomes 1 and 7 (t1q43;7q34), and addition of DNA of unknown origin to the pericentromeric regions of chromosomes 4 and 10--occurred in all of the cells of all transformed clones and in the cells of tumors that grew from them. New marker chromosomes involving the same regions of chromosomes 4 and 7 were found in several cell lines established from independent tumors. The preservation of marker chromosomes in tumor cells in the face of random loss and gain of other chromosomes suggests that these non-random aberrations were necessary for tumor formation. The presence of marker chromosomes was associated with increased expression of the c-myc gene (located at q34 on chromosome 7), the c-H-ras gene (located at q41-43 on chromosome 1) and the c-K-ras and TGF alpha genes (both located at unknown sites on chromosome 4), which we have previously shown to be highly correlated with tumorigenicity in these same transformed clonal lines (Lee et al., Cancer Res., 51, 5238-5244, 1992).

Animals

Report of an audit of nurse triage in an accident and emergency department.

The nurse triage process in an accident and emergency (A&E) department was audited as part of the nursing quality assurance programme. It was found that in most cases documentation was adequate and guidelines had been adhered to. Triage decisions were accurate in most cases using the discharge diagnosis as a bench-mark. Waiting time improvements were also seen. Triage audit was a useful tool in the continuous quality improvement effort.

Documentation

Evaluating a speech-reception threshold model for hearing-impaired listeners.

Plomp's speech reception threshold (SRT) model [R. Plomp, J. Acoust. Soc. Am. 63, 533-549 (1978)] incorporates a distortion and an attenuation factor that are both expressed in dB and, for hearing-impaired listeners, are greater than 0 dB. The distortion factor is hypothesized to affect the SRT in quiet and in noise and suggests that a hearing-impaired listener will always demonstrate a higher SRT than a normal-hearing listener. The present study examines whether this distortion factor can be explained for many listeners simply by inaudibility of a portion of the speech spectrum. SRTs were obtained from normal-hearing and mild-to-moderately hearing-impaired listeners in quiet and at various noise levels. The results indicate that, at high noise levels, when the noise, rather than the quiet threshold, becomes the dominating factor, the SRT functions of both the normal and the mild-to-moderately hearing-impaired group converge and the distortion factor diminishes to zero. Predictions were also made using an articulation index and similar convergence of the two functions was observed.

Acoustic Stimulation

Evaluating performance with high-frequency emphasis amplification.

Hearing aid fitting for individuals with high-frequency impairment has been difficult because of the limited gain available at those frequencies. Special high-frequency emphasis hearing aids have been developed in an attempt to alleviate this problem. The insertion-gain responses and changes in speech-recognition performance (in quiet and in noise, aided and unaided) were measured for a commercially available high-frequency emphasis hearing aid, using two types of speech materials (nonsense syllables, monosyllabic words). The maximum obtainable gain observed for high frequencies approximated that prescribed by the NAL-R method, but was considerably lower than that prescribed by other common prescriptive methods. Furthermore, modest improvements in speech recognition were found. When evaluating individuals with high-frequency impairment, speech materials administered in noise appeared to be the most sensitive indication of improved speech recognition. Special high-frequency emphasis speech materials (CUNY NST) were no more sensitive to improvements in performance than conventional clinical word lists (NU6).

Adult

Two experiments on the spectral boundary conditions for nonlinear additivity of simultaneous masking.

The present paper describes the results from two experiments which explored the spectral boundaries for the nonlinear additivity of simultaneous masking. The first experiment measured the threshold for detection of a 2-kHz tone in the presence of two 800-Hz-wide bands of noise that had varying degrees of spectral overlap with each other and the 2-kHz signal. Results revealed an abrupt transition from linear to nonlinear additivity of masking as the spectral separation between the two maskers varied from some overlap to none. The second experiment examined alternative explanations for the data. Explanations based on restricted-listening or distortion-product-detection hypotheses were not supported by the results of this experiment. These data indicate that nonlinear additivity of simultaneous masking holds for maskers that do not overlap within the critical band centered on the signal frequency. This interpretation is also consistent with a large body of data on the monaural and binaural summation (additivity) of loudness.

Adult

Use of an automated medication storage and distribution system.

The effects of an automated medication storage and distribution system in a hospital setting were evaluated. The Pyxis Medstation system was implemented on two nursing units at a 1000-bed tertiary-care referral hospital. The system, which is designed like an automated bank teller, dispenses items to authorized users and records all transactions. Floor-stock controlled substances and noncontrolled medications, large-volume i.v. solutions, and i.v. administration sets were stocked in the system. The system was evaluated (1) by comparing the mean patient charge capture rates for six months before and for three months after implementation, (2) by measuring nurse and pharmacy technician time required for various tasks before and after implementation, and (3) through questionnaires filled out by nurses and technicians. After the system was installed, nursing personnel spent less time on medication-related activities, charting, and documentation and more time interacting with patients. Pharmacy technicians spent more time on floor-stock activities and less time on billing activities. Nurses indicated positive attitudes toward the system features. Both nurses and pharmacy technicians indicated that the system should remain in use. After implementation, the charge capture rate for noncontrolled medications, i.v. solutions, and i.v. sets increased from 63% to 97%. This increase, extrapolated to the entire hospital, reflects $35,000 in additional revenue over the total costs of implementation of the system. Implementation of an automated medication storage and dispensing system is expected to increase hospital revenue and enable nurses to spend more time interacting with patients at this institution.

Attitude of Health Personnel