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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 415 records · Page 23Linked to original sources

Fertility rates among lead workers and professional bus drivers: a comparative study.

We examined the relationship between lead exposure and fertility among men in a retrospective cohort study. Fertility (1981-1992) of lead-exposed workers was determined from birth certificate information and was compared with that of nonexposed workers. The exposed group consisted of 4256 reproductive-age male workers reported to the New York State Heavy Metals Registry. The comparison group consisted of a random sample of male bus drivers licensed in the state of New York; these men were frequency-matched by age and residence to the men who were exposed to lead. The actual number of births among lead workers was lower than the expected number of births for that group (standardized fertility ratio [SFR] = 0.88; 95% confidence interval [CI] = 0.81-0.95), especially among those who had elevated blood lead levels for longer than 5 years (SFR = 0.43; 95% confidence interval [CI]: = 0.31, 0.59). Even after adjusting for age, race, education, and residence, workers with > 5 years of exposure had reduced likelihood of fathering a child than those with a shorter period of exposure (relative risk, 0.38; 95% CI: 0.23, 0.61). Our study indicates that men with a long duration of lead exposure might have reduced fertility.

Adult↗

Esophageal bolus transit imaged by ultrafast computerized tomography.

BACKGROUND & AIMS: Conventional transit imaging techniques detect only the solid or liquid component of a swallowed bolus within the esophagus. This study aimed to dynamically image the composition, distribution, and propulsion of esophageal contents during swallowing. METHODS: Multiple adjacent cross-sectional images of the esophagus were obtained in 7 subjects using ultrafast computerized tomography. Images from two 10-mL swallows were synchronized and analyzed for bolus distribution and propulsion, cross-sectional area, intraluminal volume, and intraluminal content. RESULTS: Both liquid and air were swallowed, with the relative distribution varying among levels. Within the ampulla, air occupied 71% of the luminal cross-sectional area. Air was propelled ahead of the liquid bolus at 17 cm/s compared with 7 cm/s for fluid (P < 0.01) and accumulation within the ampulla. Mean bolus velocity was slower through the ampulla. A variable (8-32 mL) volume of air was ingested during swallowing. CONCLUSIONS: Ultrafast computerized tomography studies during transit of a swallowed bolus through the esophagus showed substantial aerophagia and partial bolus separation with air preceding fluid. The ampulla exhibited greater distention that the tubular esophagus because the bolus accumulated at this level before transfer across the hiatus.

Adult↗

Oropharyngeal accommodation to swallow volume.

BACKGROUND & AIMS: The oropharyngeal swallow accommodates a range of bolus volumes with substantial impact on its dynamic radiographic appearance despite being a nearly reflexive sequence. The aim of this study was to analyze the mechanism of volume accommodation. METHODS: Coordination of the glossopalatal junction, velopharyngeal junction, laryngeal vestibule, and upper esophageal sphincter (UES) and intraluminal pharyngeal dimensions were measured from biplane videofluoroscopic swallowing studies in 8 volunteers during 1- and 20-mL swallows. These measurements were applied to three-dimensional reconstructions of the pharyngeal swallow, permitting analysis of their effect on intraluminal volume and propulsive function. RESULTS: Dividing the pharyngeal swallow into periods of reconfiguration, sustained reconfiguration, and offset of reconfiguration, volume accommodation occurred by a 0.2-second prolongation of reconfiguration, preserving the coordination of the onset and offset events. Augmented reconfiguration increased the dimensions of the pharyngeal chamber, caused more rapid bolus expulsion, and increased UES distention. However, maximal transphincteric flow per unit area across the UES was constant, showing its compliance. CONCLUSIONS: Volume accommodation is accomplished by augmenting and prolonging pharyngeal reconfiguration from a respiratory to deglutitive pathway. This modification in the timing of neurally mediated events is amplified by its mechanical consequences, resulting in the different cineradiographic appearance and propulsive attributes of large and small volume swallows.

Adult↗

Modification of tyrosine-3 (63) and lysine-6 of Taiwan cobra phospholipase A2 affects its ability to enhance 8-anilinonaphthalene-1-sulfonate fluorescence.

The Tyr-3 (63) and Lys-6 of Naja naja atra phospholipase A2 (PLA2) were modified with p-nitrobenzenesulfonyl fluoride and 4-chloro-3,5-dinitrobenzoate, respectively. Although the ability of the Lys-modified derivative to enhance the ANS fluorescence was lower than that observed with native PLA2, the ANS-binding affinity of the Lys-modified derivative was similar to that of the native enzyme. Modifications on Tyr-3 or/and Tyr-63 of PLA2 resulted in the complete loss of its ability to enhance the ANS fluorescence. Nevertheless, the extent of O-sulfonylation of Tyr residues was not effectively reduced by the addition of ANS. This suggests that Tyr-3 and Tyr-63 interact with the bound ANS in an aromatic ring-stacking manner. Alternatively, the incorporation of a carboxydinitrophenylated group on Lys-6 may notably perturb the nonpolarity of the ANS-binding site.

Anilino Naphthalenesulfonates↗

Augmentation of leukocyte count with G-CSF in a patient with neutropenia before In-111 WBC scintigraphy.

Neutropenia with persistent fevers and a wound infection developed in a patient with AIDS after an uncomplicated hysterectomy. After a single dose of G-CSF (granulocyte-colony stimulating factor), the WBC count transiently recovered, and an In-111 labeled WBC scan was successfully performed to exclude an intra-abdominal source of infection and to implicate the superficial wound as a source of her fevers. The patient underwent wound debridement the next day and made an uneventful recovery. This article describes a potential new role for G-CSF, namely enhancement of the WBC count in patients with neutropenia who are referred for In-111 WBC imaging to improve diagnostic yield.

Acquired Immunodeficiency Syndrome↗

Comparison of demographic and defect characteristics among different developmental stages of congenital limb reduction defects.

This study investigates how the timing of the development of limb reduction defects (LRDs) is associated with selected demographic, medical variables and defect characteristics. The LRD cases (n = 281) were ascertained from the Congenital Malformations Registry of New York State among 1983-1987 births. Cases were classified according to five stages of gestation based on when their earliest LRD developed. A control group consisted of a systematic random sample (n = 327) of non-malformed livebirths. Demographic and LRD characteristics were abstracted from birth certificates and medical charts. Among LRDs, the defects that occurred in the earlier stages of gestation were found to be more complex problems, compared with those developing in the later stages. Middle or late stage LRDs tended to occur more often with syndactyly than early stage LRDs, and had significantly higher frequencies of non-white infants compared with controls. In addition, some perinatal complications, pre-term delivery and low birthweight were positively associated with any LRD. Our findings suggest that the timing of a disturbance in limb development is important in terms of LRD characteristics. Demographics did not vary consistently with the stage of LRD development. Further studies testing this classification technique are suggested.

Adult↗

A note on the combination of estimates of a recombination fraction.

A number of ways of combining two or more independent estimates of the same recombination fraction can be found in the literature. We revisit this topic in the context of human gene mapping, and explore the value of transforming the recombination fraction to a new parameter whose log-likelihood function is more nearly quadratic. It is shown that the arcsine of the cube-root is one such function. These observations lead naturally to a way of summarizing and combining the summarized set of log-likelihood functions of a common recombination fraction. This idea is illustrated using pedigree data concerning six loci on chromosome 10 from the CEPH consortium. A comparison is also made with the method of summarizing and combining using 'equivalent numbers' of recombinants and informative meioses.

Chromosome Mapping↗

Carboxypeptidase G2 rescue after high-dose methotrexate.

PURPOSE: This study was a pilot project to assess the safety and efficacy of carboxypeptidase G2 (CPG2) rescue from high-dose (HD) methotrexate (MTX) in patients with recurrent cerebral lymphoma. PATIENTS AND METHODS: Four patients with recurrent primary CNS lymphoma (PCNSL) were studied. Patients received 3.0 g/m2 MTX infused over 2 hours. Twelve hours after the start of MTX, 50 U/kg CPG2 was infused; a second dose of CPG2 was given 6 hours after the first. Blood and CSF were collected and assayed for levels of MTX, CPG2, and 2,4-diamino-N10-methylpteroic acid (DAMPA), a cleavage product of MTX after CPG2. Serum was collected for at least 2 weeks after administration of MTX-CPG2 to assess anti-CPG2 activity antibodies. RESULTS: All patients had at least a 2-log decline in plasma MTX levels to the subtherapeutic range within 5 minutes of CPG2 administration. The second dose of CPG2 did not further diminish the already low plasma MTX level. DAMPA appeared and was detected as the plasma MTX concentration decreased. CSF MTX concentration remained elevated for 4 hours after CPG2, and its decline followed first-order kinetics. Anti-CPG2 activity antibodies were not detected in any patient. No MTX or CPG2 toxicity was observed. CONCLUSION: CPG2 rescue is a safe, effective alternative to leucovorin rescue after HD MTX and may prove particularly useful for the treatment of MTX-sensitive CNS tumors, as it does not affect CSF MTX levels.

Antimetabolites, Antineoplastic↗

Zebrafish pigmentation mutations and the processes of neural crest development.

Neural crest development involves cell-fate specification, proliferation, patterned cell migration, survival and differentiation. Zebrafish neural crest derivatives include three distinct chromatophores, which are well-suited to genetic analysis of their development. As part of a large-scale mutagenesis screen for embryonic/early larval mutations, we have isolated 285 mutations affecting all aspects of zebrafish larval pigmentation. By complementation analysis, we define 94 genes. We show here that comparison of their phenotypes permits classification of these mutations according to the types of defects they cause, and these suggest which process of neural crest development is probably affected. Mutations in eight genes affect the number of chromatophores: these include strong candidates for genes necessary for the processes of pigment cell specification and proliferation. Mutations in five genes remove part of the wild-type pigment pattern, and suggest a role in larval pigment pattern formation. Mutations in five genes show ectopic chromatophores in distinct sites, and may have implications for chromatophore patterning and proliferation. 76 genes affect pigment or morphology of one or more chromatophore types: these mutations include strong candidates for genes important in various aspects of chromatophore differentiation and survival. In combination with the embryological advantages of zebrafish, these mutations should permit cellular and molecular dissection of many aspects of neural crest development.

Adaptation, Physiological↗

Transcriptional control of cell phenotypes in the neuroendocrine system.

A fundamental aspect of the development of complex organ systems is a requirement for precise temporal and spatial coordination in the genesis of tissues of distinct embryonic origins, in order to form functional units required for physiological homeostasis and survival. Such a requirement is particularly well exemplified in mammalian development in the formation of the hypothalamic-pituitary axis. Neuronally expressed POU domain factors might exert effects on terminal differentiation events similar to those of Pit-1 in the maturation of anterior pituitary gland cell phenotypes. Neurons comprising the endocrine hypothalamus develop in tandem with their ultimate target, the pituitary gland, and arise from a primordium in which three related class III POU domain factors-Brn-2, Brn-4, and Brn-1-are initially co-expressed. These factors subsequently exhibit stratified patterns of ontogenic expression, correlating with the appearance of distinct neuropeptides that define three major endocrine hypothalamic cell types. Deletion of the Brn-2 genomic locus affects terminal differentiation and/or maintenance of hypothalamic neurosecretory neurons and development of the posterior pituitary gland. Thus, both neuronal and endocrine components of the hypothalamic-pituitary axis are critically dependent upon the action of specific POU domain factors at a penultimate step in the sequential events that underlie the appearance of mature cellular phenotypes.

Amino Acid Sequence↗

Mixed agonist/antagonist activity of an FK-506-related immunosuppressant: biological and biochemical characterization.

FK-506 blocks T cell activation by preventing lymphokine gene transcription through formation of a complex with FKBP12 that inhibits calcineurin phosphatase activity. Immunosuppressive FK-506 analogs (agonists) have been generated whose potency correlates with calcineurin inhibition. Nonimmunosuppressive antagonist analogs have also been identified, including L-685,818, which binds to FKBP12 but does not inhibit calcineurin. We describe a novel property of FK-506 analog, characterized as a mixed agonist/antagonist immunosuppressive activity. It is displayed by L-688,617, the 32 O-methoxyethoxymethyl derivative of the agonist L-683,590 (C21-ethyl). Although it binds to FKBP12 similarly to L-683,590, L-688,617 incompletely suppressed T cell proliferation induced by optimal activation and enhanced that induced by supraoptimal activation. In the latter situation, L-688,617 suppressed IL-2 production only partially but blocked activation-driven cell death. Moreover, a 1000-fold molar excess of L-688,617 antagonized the immunosuppressive activity of L-683,590. L-688,617 inhibited calcineurin phosphatase activity in cells only partially. The unique agonist/antagonist activity of L-688,617 may therefore reflect its high affinity for FKBP12, combined with a reduced ability of the drug-FKBP12 complex to inhibit calcineurin function. However, in a cell-free system, L-688,617 completely blocked this function when a large excess of FKBP12 over calcineurin was present, suggesting that the intracellular concentration of FKBP12 may be a limiting factor that prevents full agonist activity of L-688,617 in cells.

Animals↗

Theory of wear as related to the Björk-Shiley Delrin disc heart valve.

BACKGROUND AND AIMS OF THE STUDY: Mechanical wear is an important consideration for the Björk-Shiley Delrin (BSD) heart valve, the disc of which is periodically impacted against the inlet strut by the momentum of the blood flow during closure. Impact wear theory was used in designing experiments as well as establishing theoretical evaluation and projections of wear life. MATERIALS AND METHODS: The experimental apparatus involved a pivotal hammer device where the striking face could be varied by the inclusion of distinct spherical shapes; the sharper the radius, the higher the contact stress induced. The striking speed could be varied between one and three m/s, and the repetition rate between 2-50 Hz. Blood was simulated with an aqueous 42% glycerol solution. The same wear mechanism was induced on Delrin occluder disc specimens as the one governing the wear observed in Delrin occluder discs of some of the explanted BSD heart valves; thus two wear parameters, c and g, were established for the prediction of wear in BSD implants. The experimental runs were repeated on as many as four simultaneous specimens, for up to 7.5 x 10(7) cycles. RESULTS: The wear history was found to comprise three distinct regions, corresponding to (a) initial plastic deformations; (b) zero wear; and (c) measurable wear. The zero wear region produced very little change in the contact dimensions, and represented a fatigue threshold to the progress of a wear scar. Procedures for analytical establishment of the zero wear limit are outlined in the paper. Measurable wear was governed by the process of increasing conformance between the repetitively contacting surfaces. The differential equation of wear was then used with the physical parameters c and g previously determined experimentally. CONCLUSION: The maximum depth of the wear scar after cycling the equivalent of 20 years was predicted to be 278 microns. This value appears to represent a safe dimension for BSD heart valves.

Biocompatible Materials↗

Multipoint linkage analysis via Metropolis jumping kernels.

Multipoint linkage analysis is being performed routinely in medical genetic studies to localize disease genes. This likelihood-based method is very computationally intensive. Exact computations are thus formidable for problems with large number of genetic markers and complex pedigrees. This paper proposes a Monte Carlo method to estimate the required likelihoods. The space of multilocus genotypes is sampled using a hybrid algorithm with a mixture of Gibbs samplers and Metropolis jumping kernels. These samples are essentially realizations of a Markov chain, and are distributed approximately according to the conditional genotype distribution given the observed phenotypic data. We present a simulation study with several eight-point analyses to demonstrate the feasibility of the current method.

Algorithms↗

[Observation and analysis of postburn changes in substance P (SP) and SP peptidergic nerve fibers in the intestine of rat].

Substance P (SP) was measured by radioimmunoassay (RIA) and SP peptidergic nerve fibers were identified by Immunohistochemistry (IHC) in the intestinal wall of rats (TBSA 30% and with full-thickness burn) during 72 hours after burn. The results were as follows: (1) SP increased significantly at 1 hr and 4 hr postburn, then decreased markedly 8 hr later, and the low was maintained up to 72 hr. (2) The significant changes in SP peptidergic nerve fibers in the villi after burn were found with immunohistochemical studies including the morphology, distributive densities and SP contents of the SP peptidergic nerve fibers. The results from image analysis showed that the distributive densities of the nerve fibers elevated distinctly in 1 hr group, then dropped at 8 hr and 12 hr and finally elevated again. The results indicated that, the SP release might occur leading to SP consumption in the intestinal wall of rats after burn. It is possible that SP contributes to the postburn intestinal lesion in rats. The SP peptidergic nerve fibers in villus have a direct effect on the damage of intestinal mucosal barrier.

Animals↗

[A sample survey and multiple factor analysis on asthma in urban area of Shanghai].

OBJECTIVE: To estimate the prevalence of asthma in urban residents of Shanghai in 1990 and evaluate the risk factors of asthma. METHODS: A cluster uneven random survey of asthma was conducted among 36,872 urban residents, 5/1000 of the population of the city. The asthmatics were suspected based upon case history, and then confirmed by home visit and further investigation. Single factor and unconditional logistic regression analysis were employed to evaluate the risk factors of asthma. RESULTS: The accumulative prevalence of asthma was 1.53% for age group 0-35 and it was higher in male (1.74%) than in female (1.31%). Sex, age and type of living house were possible risk factors. The prevalences were much higher among people with history of TB and pneumonia of which the values of relative risks were 2.53 and 4.95, respectively. Histories of food, drug and other kinds of hypersensitivity were significantly related to the history of asthma. CONCLUSION: Several risk factors possibly associated with asthma were identified in Shanghai area.

Adolescent↗

[Role of area postrema on DOCA-salt induced hypertension in rat].

OBJECTIVE: To determine the effect of area postrema AP on DOCA-salt induced hypertension in rat, with emphasis on renal hemodynamics. METHOD: Blood pressure, salt and water balances and renal hemodynamics were observed in AP ablated and sham-operated rats treated with DOCA-salt. RESULTS: In AP intact (API) rats, after one week of DOCA-salt treatment BP began elevating to statistical significance at the end of the second week (MAP 15.9 +/- 0.7 vs. 13.5 +/- 0.5 kPa), followed by a plateau period from the third to fifth week. In AP ablated (APX) rats, BP raised during the first week of DOCA-salt treatment. However, the elevation gradually disappeared and BP returned to baseline at the fifth week. Sodium balance study showed that DOCA-salt treatment induced significant sodium retention in API rat, while the sodium metabolism remained stable in APX group except in the first week. Basal renal hemodynamic parameters (GFR, RPF, UNaV, UV) were not changed at neither the beginning nor the end of the study. However, a small dose of hypertonic saline (7% NaCl 0.3 ml) injection caused a brisk rising of these four parameters in APX but not API group. CONCLUSION: AP plays an important role in normal salt and water metabolism and might be involved in pathogenesis of DOCA-salt hypertension through regulation for renal hemodynamics and body fluid homeostasis.

Animals↗