Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 505 records · Page 28Linked to original sources

PubMed1993

Evaluation of congenital limb reduction defects in upstate New York.

Limb reduction defects (LRD), reported to the Congenital Malformations Registry in upstate New York between 1983-1987, were investigated in terms of LRD classification, parental demographics, and LRD characteristics. After excluding LRD with chromosome abnormalities, we followed guidelines developed by the European Congenital Anomaly Surveillance Consortium (EUROCAT) to classify 271 LRD into six groups based on similar patterns of embryological failure. The descriptive analysis indicated a prevalence of 0.45 per 1,000 births (stable over 5 years) for LRD diagnosed during the first 2 years of life. Among 271 LRD cases, 95 were classified as terminal transverse (35.1%), 71 as split limbs (26.2%), 36 as preaxial (13.3%), 32 as postaxial (11.8%), 26 as intercalary (9.6%), and 11 as multiple types (4.1%). In cases with multiple limb involvement (28.4%), two thirds had the same type of LRD in each limb. The multiple types and preaxial groups showed the most distinctive characteristics: they had the highest frequency of suspected syndromes, other birth defects, and syndactyly compared to the other LRD. There were no significant differences in the distribution of demographic variables among different LRD types. Consideration of the incidence and characteristics of LRD by classifying them into these distinct subgroups may be useful for evaluating possible mechanisms of malformation.

Abnormalities, Multiple↗

PubMed1993

Shape, volume, and content of the deglutitive pharyngeal chamber imaged by ultrafast computerized tomography.

BACKGROUND: Conventional radiographic techniques image only the silhouettes of the deglutitive pharyngeal chamber. This study aimed to accurately image the horizontal plane shape and content of the pharynx during swallowing. METHODS: Dynamic computerized tomography images of the pharynx were obtained at the rate of 17 per second during swallowing. Multiple adjacent levels were imaged in eight subjects and a single level was scanned in four subjects during swallows of varied volume. Images were analyzed for area, volume, and the bolus fraction of the deglutitive pharyngeal chamber. RESULTS: The deglutitive chamber enlarged to approximately 24 mL (during tongue loading) compared with a preswallow pharyngeal volume averaging 15 mL. Throughout the 10 mL swallows, the bolus occupied less than 30% of the lumen regardless of axial level. The bolus fraction of the deglutitive chamber increased with swallow volume, as did the dimensions of the upper esophageal sphincter and the bolus velocity through the upper esophageal sphincter. CONCLUSIONS: The deglutitive pharyngeal chamber was typically approximately 15 mL > the bolus volume, implying that an obligatory 15 mL of air was swallowed under these test conditions. Most swallowed air originated as air trapped within the pharynx and larynx as the oropharynx was sealed from above and below.

Adult↗

PubMed1993

Deglutitive tongue action: volume accommodation and bolus propulsion.

BACKGROUND: Swallow function is best analyzed in components because discrete component failure may be compensated for with devised maneuvers, postures, or biofeedback techniques. The present investigation examined normal deglutitive tongue function. METHODS: Biplane videofluoroscopy synchronized with intraluminal manometry was performed in eight volunteers. Tongue surface motion was characterized as centripetal or centrifugal along seven equiangular rays emanating from the tongue center during 1-, 5-, 10-, and 20-mL swallows. RESULTS: The tongue perimeter remained in contact with the alveolar ridge while the central groove exhibited centripetal and subsequent centrifugal motion that, in conjunction with the pharyngeal walls, created an oropharyngeal propulsive chamber and then expelled that chamber's contents into the hypopharynx. Intrabolus propulsive pressure was generated when the initially expansive propulsive chamber volume contracted to the test bolus volume. Because pharyngeal chamber action cycle timing was relatively constant among bolus volumes, vigorous expulsion occurred with large volumes but relatively delayed, sluggish expulsion occurred with smaller volumes. CONCLUSIONS: Deglutitive tongue functions include bolus containment, volume accommodation, and the major contributor to bolus propulsion.

Adult↗

PubMed1993

Pharmacological evaluation of iodo and nitro analogs of delta 8-THC and delta 9-THC.

One aspect of cannabinoid structure-activity relationships (SARs) that has not been thoroughly investigated is the aromatic (A) ring. Although halogenation of the side chain enhances potency, our recent observation that iodination of the A ring also enhanced activity was surprising. The purpose of this investigation was to establish the steric and electrostatic requirements at these sites of the cannabinoid molecule via molecular modeling, while determining pharmacological activity. Molecular modeling was performed using the Tripos molecular mechanics force field and the semiempirical quantum mechanical package AM1. The Ki values for novel cannabinoids were determined in a [3H]CP-55,940 binding assay and ED50 values generated from four different evaluations in a mouse model. The present studies underscore the increase in potency produced by a dimethylheptyl (DMH) side chain. Trifluoro substitutions on the pentyl side chain, or bromination of the DMH side chain, had little effect on the pharmacological activity. Any substitution at the C4 position of the aryl ring resulted in a loss of activity, which appears to be due to steric hindrances. Nitro, but not iodo, substitution at the C2 position essentially produces an inactive analog, and the drastic alteration of the electrostatic potential appears to be responsible. The altered pharmacological profile of the 2-iodo analog seems to be related to an alteration in the highest occupied molecular orbital because there is no alteration in the electron density map compared to delta 8-tetrahydrocannibinol.

Analgesics↗

PubMed1993

In vitro and in vivo testing of the dopamine D1 ligand [123I]SCH 23982 with respect to its potential application in SPET investigations.

[123I]SCH 23982, a dopamine D1 ligand, was labelled in a large scale process and then tested in vitro for binding to rat brain sections and membranes. Because of the promising values of KD = 1.5 x 10(-10) M and Bmax = 0.7 x 10(-11) mol/g, in vivo evaluation was performed on rats and normal volunteers to test its possible usefulness for SPET imaging. In competition experiments, a higher binding in the presence of sulpiride was found while ketanserin displaced [123I]SCH 23982 only at a 10,000-fold excess. Differences between rats and men were seen with respect to their metabolism. SPET investigations failed because the washout of [123I]SCH 23982 was too rapid.

Aged↗

PubMed1993

Achieving irreducibility of the Markov chain Monte Carlo method applied to pedigree data.

Markov chain Monte Carlo (MCMC) methods have been explored by various researchers as an alternative to exact probability computation in statistical genetics. The objective is to simulate a Markov chain with the desired equilibrium distribution. If the transition kernel is aperiodic and irreducible, then convergence to the equilibrium distribution is guaranteed; realizations of the Markov chain can thus be used to estimate desired probabilities. Aperiodicity is easily satisfied, but, although it has been shown that irreducibility is satisfied for a diallelic locus, reducibility is a potential problem for a multiallelic locus. This is a particularly serious problem in linkage analysis, because multiallelic markers are much more informative than diallelic markers and thus highly preferred. In this paper, the authors propose a new algorithm to achieve irreducibility of the Markov chain of interest by introducing an irreducible auxiliary chain. The irreducibility of the auxiliary chain is obtained by assigning positive probabilities to a small subset of the genotypic configurations inconsistent with the data, to bridge the gap between the irreducible sets.

Algorithms↗

PubMed1993

Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer.

PURPOSE: This study was performed to assess the short- and long-term toxicities and the impact on relapse pattern and survival of postoperative intraperitoneal (IP) cisplatin and fluorouracil (FU) plus systemic intravenous (IV) FU as adjuvant therapy for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2N1-2M0 or T3-4N(any)M0). PATIENTS AND METHODS: Starting 14 to 28 days after potentially curative resection of primary gastric cancers, 35 patients were given IP cisplatin 25 mg/m2 and FU 750 mg daily for 4 days; FU 750 mg/m2 was concurrently given as a continuous 24-hour i.v. infusion. Five cycles of therapy delivered at 1-month intervals were used. RESULTS: After a median follow-up of 24 months, 51% of patients remain alive and free of disease. Sixteen patients have recurred; 13 of 16 had an intraabdominal component, whereas three had extraabdominal failure only. Two major treatment-related toxicities were noted: neutropenia and a late toxicity of peritoneal fibrosis (sclerosing encapsulating peritonitis [SEP]). There was one postoperative death. Eleven patients underwent second laparotomy: five patients had SEP, two patients had bowel obstruction from adhesions unrelated to SEP, and four patients had recurrent cancer. Potential causes of SEP included an alkaline pH of infused FU and cisplatin that possibly led to activation of cisplatin before infusion. CONCLUSION: IP cisplatin and FU and concurrent systemic FU is a tolerable adjuvant therapy in the postoperative setting for patients with resected gastric cancer. The recommended dosage schedule with this technique is cisplatin 25 mg/m2 and FU 750 mg total dose IP with FU 500 mg/m2 as a continuous 24-hour infusion daily for days 1 to 4. SEP as a late toxicity, which was observed in 15% of patients, is treatable by surgical lysis of adhesions.

Adenocarcinoma↗

PubMed1993

[Mitochondrial DNA polymorphism of cattle (Bos taurus) and mithun (Bos frontalis) in Yunnan Province].

An analysis of cleavage patterns of mtDNA by restriction endonuclease was performed for fifteen Yunnan native cattle, two Kunming black and white cow, and one mithun (Bos frontalis). Two types of mtDNA molecule were detected in Yunnan native cattle: five individuals showed the type of yellow cattle (Bos taurus), the other ten showed that of zebu cattle (Bos indicus), suggesting their European and zebu origins. The mtDNA in Kunming black and white cow also consists of two restriction types. The mithun mtDNA showed the type of zebu cattle, indicating the close relationship between the origins of mithun and zebu cattle.

Animals↗

PubMed1992

Production of germ-line chimeras in zebrafish by cell transplants from genetically pigmented to albino embryos.

To determine whether embryonic cells transplanted from one zebrafish embryo to another can contribute to the germ line of the recipient, and to determine whether pigmentation can be used as a dominant visible marker to monitor cell transplants, we introduced cells from genetically pigmented (donor) embryos to albino recipients at midblastula stage. By 48 hr many of the resulting chimeras expressed dark pigment in their eyes and bodies, characteristics of donor but not albino embryos. By 4-6 weeks of age pigmentation was observed on the body of 23 of 70 chimeras. In contrast to fully pigmented wild-type fish, pigmentation in chimeras appeared within transverse bands running from dorsal to ventral. Pigmentation patterns differed from one fish to another and in almost every case were different on each side of a single fish. At 2-3 months of age chimeras were mated to albino fish to determine whether pigmented donor cells had contributed to the germ line. Of 28 chimeric fish that have yielded at least 50 offspring each, 5 have given rise to pigmented progeny at frequencies of 1-40%. The donor cells for some chimeras were derived from embryos that, in addition to being pigmented, were transgenic for a lacZ plasmid. Pigmented offspring of some germ-line chimeras inherited the transgene, confirming that they descended from transplanted donor cells. Our ability to make germ-line chimeras suggests that it is possible to introduce genetically engineered cells into zebrafish embryos and to identify the offspring of these cells by pigmentation at 2 days of age.

Albinism↗

PubMed1992

Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth.

Limonene has been shown to be an effective, nontoxic chemopreventive and chemotherapeutic agent in chemically induced rat mammary-cancer models. The present study characterized circulating metabolites of limonene in female rats and determined their effects on cell growth. Metabolism of limonene was analyzed in plasma extracts by gas chromatography. Rapid conversion of limonene to two major metabolites was detected. These metabolites comprised more than 80% of the circulating limonene-derived material at 1 h after administration and thereafter, whereas limonene itself accounted for only 15%. The metabolites were characterized by mass spectroscopy and infrared spectroscopy. The probable structures were synthesized, and identities were confirmed by comparison of retention times and mass spectra. The two major circulating metabolites of limonene were found to be perillic acid and dihydroperillic acid. We have previously reported that limonene, perillic acid, and dihydroperillic acid inhibit the posttranslational isoprenylation of p21ras and other 21- to 26-kDa cell-growth-associated proteins in NIH3T3 cells and in mammary epithelial cells. In the present study, perillic acid was found to inhibit cell growth in a dose-dependent manner. Thus, perillic acid and dihydroperillic acid, the two major circulating metabolites of limonene in the rat, are more potent inhibitors of protein isoprenylation than is limonene, and perillic acid is also a more potent inhibitor of cell growth. These data raise the possibility that the antitumor effects of limonene in vivo may be mediated via perillic acid and, perhaps, other metabolites.

3T3 Cells↗

PubMed1992

Pharyngeal clearance during swallowing: a combined manometric and videofluoroscopic study.

The deglutitive pharyngeal contraction was analyzed using simultaneous videofluoroscopic and manometric studies of eight volunteers. Anterior, posterior, and longitudinal movements of the pharyngeal surfaces, relative to the cervical vertebrae, were measured during swallows of 5 and 10 mL of liquid barium. Profound pharyngeal shortening during bolus transit through the pharynx eliminated access to the larynx and elevated the upper esophageal sphincter to within 1.5 cm of the retrolingual pharynx. Bolus head movement through the pharynx preceded the propagated pharyngeal contraction and registered manometrically as a slight intrabolus pressure before the major pressure complex. Contraction in the horizontal plane began after bolus head transit and culminated with stripping of the bolus tail through the pharynx. Prolonged upper sphincter opening with the larger-volume swallows resulted from a delayed onset rather than altered propagation of the horizontal pharyngeal contraction. It is concluded that the propagated pharyngeal contraction facilitates pharyngeal clearance but has a minimal role in the process of bolus propulsion during swallowing. The propagated contraction works in concert with profound pharyngeal shortening to minimize hypopharyngeal residue after a swallow.

Adult↗

PubMed1992

A risk-based prospective payment system that integrates patient, hospital and national costs.

We suggest that a desirable form for prospective payment for inpatient care is hospital average cost plus a linear combination of individual patient and national average cost. When the coefficients are chosen to minimize mean squared error loss between payment and costs, the payment has efficiency and access incentives. The coefficient multiplying patient costs is a hospital specific measure of financial risk of the patient. Access is promoted since providers receive higher reimbursements for risky, high cost patients. Historical cost data can be used to obtain estimates of payment parameters. The method is applied to Medicare data on psychiatric inpatients.

Costs and Cost Analysis↗

PubMed1992

Large scale preparation strategy for labelling of [123I]-SCH 23982, a dopamine D1 receptor binding agent.

The labelling of the D1 antagonist SCH 23982 with 123I was studied in detail by following the nucleophilic and electrophilic approaches and the reaction conditions were optimized. The product was purified by reversed phase HPLC with a phosphoric acid/EtOH mixture which simply has to be neutralized and diluted before injection. Its binding was tested in vitro with rat striatal membranes proving the high affinity to D1 and very low affinity to D2 receptors.

Benzazepines↗

PubMed1992

Noncontiguous injuries of the spine.

A total of 372 consecutive spinal injury patients were evaluated at the Regional Spinal Cord Injury Center of Delaware Valley. Of these, 39 patients (10.5%) were found to have noncontiguous spinal column injuries. Fewer than half of the patients in our series could be classified into previous classification systems (Calenoff, Gupta) of noncontiguous spinal fractures. Fifteen fractures in 12 patients were missed on presentation on admission and 25% of these patients had a progressive neurologic deficit as a result of improper initial immobilization. The location of missed fractures were found to be primarily at the extremes or junctures of the spine (i.e., cervicothoracic, thoracolumbar). Complete spinal roentgenographic evaluation is recommended in the workup of suspected spinal column injury patients, and additional imaging modalities (i.e., tomograms, computed tomography scans, and magnetic resonance imaging) may be necessary in those areas of the spine difficult to visualize.

Adolescent↗

PubMed1992

The vaccinia virus B1R gene product is a serine/threonine protein kinase.

The nucleotide sequence of the vaccinia virus open reading frame B1 predicts a polypeptide with significant sequence similarity to the catalytic domain of known protein kinases. To determine whether the B1R polypeptide is a protein kinase, we have expressed it in bacteria as a fusion with glutathione S-transferase. Affinity-purified preparations of the fusion protein were found to undergo autophosphorylation and also phosphorylated the exogenous substrates casein and histone H1. Mutation of lysine 41 to glutamine within the conserved kinase catalytic domain II abrogated protein kinase activity on all three protein substrates, supporting the notion that the protein kinase activity is inherent to the B1R polypeptide. Casein and histone H1 were phosphorylated on serine and threonine residues. The B1R fusion protein was phosphorylated on a threonine residue(s) by an apparently intramolecular mechanism. The autophosphorylation reaction resulted in phosphorylation of the glutathione S-transferase portion of the fusion and not the protein kinase domain. The protein kinase activity of B1R was specific for ATP as the phosphate donor; GTP was not utilized to a detectable extent. Immunoblotting experiments with anti-B1R antiserum showed that the protein kinase is located in the virion particle. Chromatography of virion extracts resulted in separation of the B1R protein kinase from the bulk of the total protein kinase activity, indicating that multiple protein kinases are present in the virion particle and that B1R is distinct from the previously described vaccinia virus-associated protein kinase.

Adenosine Triphosphate↗

PubMed1992

Closure mechanisms of laryngeal vestibule during swallow.

This study examined the temporal effects of bolus volume on closure of the laryngeal vestibule at the arytenoid to epiglottic base and the mobile portion of the epiglottis, the temporal relationships between these levels of airway closure and cricopharyngeal opening for various bolus volumes, and the mechanisms responsible for these two levels of airway protection during deglutition. Closure of the laryngeal vestibule progressed inferiorly to superiorly at all bolus volumes. Duration of closure of the airway at the arytenoid to epiglottic base increased systematically with bolus volume, as did the duration of descent of the epiglottis below horizontal. Closure at the arytenoid to epiglottic base occurred earlier in relation to maximal laryngeal elevation as bolus volume increased. In contrast, descent of the epiglottis to horizontal and the temporal relationship between closure of the airway at the arytenoid to epiglottic base and cricopharyngeal opening were independent of bolus volume. These findings indicate a tightly organized neural program for some pharyngeal swallow events with systematic variability with volume in other pharyngeal events, possibly modulated by afferent input from the periphery. The neuromuscular mechanisms responsible for closure of the airway at the arytenoid to epiglottic base and at the mobile epiglottis appear to be quite different. Closure at the arytenoid to epiglottic base is apparently under direct neural control by active anterior tilting of the arytenoid cartilage and posterior projection of the epiglottic base as the larynx elevates, whereas epiglottic downward movement to closure is the biomechanical effect of hyolaryngeal movement, downward bolus movement, and tongue base retraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Processing of surfactant protein B proprotein by a cathepsin D-like protease.

Surfactant protein B (SP-B) is a hydrophobic peptide of relative molecular weight (M(r)) = 8,000 that is associated with pulmonary surfactant phospholipids. SP-B is synthesized by the alveolar type II epithelial cell as a proprotein of M(r) = 42,000 which requires at least two proteolytic cleavages to generate the 79 residue mature SP-B peptide. We have previously reported that cleavage of the NH2-terminal propeptide, to generate a processing intermediate of M(r) = 25,000, occurs in close temporal approximation to secretion. In the present study we demonstrate that SP-B proprotein, isolated from stably transfected Chinese hamster ovary cells, is processed to M(r) = 25,000 by a crude type II cell membrane fraction but not by intact type II cells or type II cell conditioned media. In vitro processing of the proprotein by the type II cell membrane preparation resulted in release of a single peptide of M(r) = 16,000-17,000, which was detected by antiserum directed against antigenic epitopes in propeptide of the precursor. SP-B processing activity was extracted by Na2CO3 lysis of the type II cell membrane preparation, had a pH optimum of 5.0-6.0, and was inhibited by 10(-7) M pepstatin A, suggesting that the NH2-terminal peptide of the precursor is cleaved by an aspartyl protease. Consistent with this hypothesis, processing of SP-B by a crude type II cell membrane preparation was blocked by antiserum directed against the aspartyl protease cathepsin D; further, purified cathepsin D efficiently processed the SP-B precursor to M(r) = 25,000. Collectively these results suggest that cleavage of the NH2-terminal propeptide of the SP-B precursor is mediated by cathepsin D or a cathepsin D-like protease localized within the secretory pathway of the type II epithelial cell.

Animals↗

PubMed1992

Treatment of murine primary brain tumors with systemic interleukin-2 and tumor-infiltrating lymphocytes.

Methods have recently been described for the isolation and expansion of lymphocytes that have trafficked into animal and human tumors. These CD8-positive tumor-infiltrating lymphocytes (TIL's) have exceptional trafficking ability to, and efficacy against, tumor targets in extracranial sites. Prior to Phase I clinical trials for patients with gliomas, adoptive immunotherapy with TIL's was studied in a mouse model of primary brain tumors to determine if intracerebral tumors have a similar response. Glioma 261 (GL261) tumors were grown in the subcutaneous space of C57BL/6 mice. After enzymatic digestion, the cells were incubated in vitro with interleukin-2 (IL-2) until a confluent population of T lymphocytes was present. The in vitro efficacy of these TIL's was tested against fresh GL261 targets with a chromium release assay; the in vivo efficacy was tested against GL261 tumors in the liver and against irradiated and nonirradiated GL261 tumors in the brain. Mice received one of the following: intraperitoneal saline; intraperitoneal IL-2 (7500 to 50,000 U three times daily for 5 days); IL-2 plus intravenous TIL's (1 to 3 x 10(7) cells); 10 Gy cranial irradiation; irradiation plus IL-2; or irradiation plus IL-2 plus TIL's. The TIL preparation killed 77% of tumor targets in 4 hours at an effector:target ratio of 100:1. In animals with GL261 tumors in the liver, at 2 weeks there were 93 +/- 37, 128 +/- 45, and 21 +/- 14 liver metastases in the control, IL-2, and IL-2 plus TIL groups, respectively. However, in animals with GL261 tumors in the brain, no treatment group had an increased survival rate compared to the control group. It is concluded that, although TIL and IL-2 immunotherapy can be used effectively to treat brain tumors in vitro and at sites outside the central nervous system, it is ineffective against the same type of tumor in the brain. Different methods of delivery or different combinations of these immunomodulators may be more effective; however, based on these findings, treatment of patients with IL-2 and TIL cannot be recommended until efficacy has been demonstrated in an animal model.

Animals↗