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Biomedical subjects

L Hsu

Publications and source records attributed to L Hsu.

At least 127 records · Page 7Linked to original sources
PubMed1994

Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden.

We followed 18 multiple sclerosis patients clinically and with repeated brain MRIs with and without gadolinium for over 1 year. Clinical evaluations included scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI) scale. There was a significant correlation between the change in EDSS or AI and the change in number of lesions on MRI and between cumulative number of lesions on MRI and cumulative change in EDSS or AI. Our findings support the validity of MRI as a measure of clinical activity and potentially as an objective quantitative outcome measure for assessing response to therapy.

Adult↗
PubMed1994

Image analysis and diagnostic classification of hepatocellular carcinoma using neural networks and multivariate discriminant functions.

BACKGROUND: Hepatocellular carcinoma (HCC) is often difficult to diagnose in cytologic material and small tissue biopsies since histomorphologic information is minimal or absent. The potential for misdiagnosis is greatest in attempting to discriminate well-differentiated HCC from dysplastic hepatocytes in cirrhosis. We investigated the feasibility of developing artificial intelligence classification methods based on nuclear image analysis data for use as adjuncts to the morphologic diagnosis of HCC. EXPERIMENTAL DESIGN: Ninety hematoxylin-eosin stained histologic slides including 56 with well- to poorly differentiated HCC and 34 showing a morphologic continuum from normal to markedly dysplastic benign hepatocytes were assembled from four laboratories. A relatively inexpensive PC-based image analysis system was used to measure 35 nuclear morphometric and densitometric parameters of 100 nuclei in each specimen. The data were randomized into classification training and testing sets containing equal numbers of benign and HCC samples. Objective diagnostic classification criteria for HCC based on neural networks and multivariate discriminant functions (DFs) were developed for the most discriminatory subsets of morphometric, densitometric, and combined morphometric/densitometric variables as selected by stepwise discriminant analysis of training data. RESULTS: Morphometric parameters provided the best results with the following testing data positive and negative predictive values (PV+ and PV-) for HCC classification: 86.2% PV+ and 81.3% PV- for a linear DF, 85.7% PV+ and 76.5% PV- for a quadratic DF and 100% PV+ and 85.0% PV- for a neural network. CONCLUSIONS: Our results demonstrate that nuclear image analysis-based objective classification criteria for HCC can be developed using artificial intelligence methods and that histologic material prepared at different institutions can be reliably classified. Neural networks for HCC classification were superior to linear and quadratic DFs. Morphometric data yielded the best results compared with densitometric or combined morphometric/densitometric data.

Carcinoma, Hepatocellular↗
PubMed1993

An analysis of dorsal root ganglia differentiation using three tissue culture systems.

The histogenesis of the dorsal root ganglia of chick embryos (ages 3 to 9 days) was followed in three different tissue culture systems. Organotypic explants included dorsal root ganglia connected to the lumbosacral segment of the spinal cord or isolated explants of the contralateral ganglia. Additionally, dissociated monolayer cultures of ganglia tissue were established. The gradual differentiation of progenitor neuroblasts into distinct populations of large ventrolateral and small dorsomedial neurons was observed in vivo and in vitro. Neurites developed after 3 days in the presence or absence of nerve growth factor in the medium. In contrast, autoradiographic analysis indicates that [3H]thymidine incorporation in neuronal cultures differed significantly from intact embryos. In vivo, the number of neuronal progenitor cells labeled with [3H]thymidine decreased in older embryos; in vitro, uptake of [3H]thymidine label was not observed in ganglionic progenitor cells regardless of the age of the donor embryo or the type of culture system. Lack of proliferation in ganglionic progenitor cells was not due to degeneration because vital staining and uptake of [3H]deoxyglucose indicated that neurons were metabolically active. Furthermore, the block in mitotic activity in vitro was limited to presumptive ganglionic neuronal cells. In the ependyma of the spinal cord segment connected to the dorsal root ganglia, neuronal progenitor cells were heavily labeled as were non-neuronal cells within both spinal cord and ganglia. Our results suggest that in vitro conditions can promote the differentiation of sensory neurons from early embryos (E3.5-4.5) without proliferation of progenitor cells.

Acetylcholinesterase↗
PubMed1993

Neurite outgrowth and protein phosphorylation in chick embryonic sensory ganglia induced by a brief exposure to 12-O-tetradecanoylphorbol 13-acetate.

An exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) at 20 nM for as short as 30 min was sufficient to elicit neurite outgrowth from explanted chick embryonic sensory ganglia. Attachment of the ganglia to the collagen-coated substratum during exposure to TPA was essential for subsequent neurite outgrowth. Pulse-labeling with [35S]-methionine indicated no significant difference in protein synthesis between control and TPA-treated ganglia. In vitro phosphorylation assay revealed a prominent protein kinase C substrate with an apparent molecular mass of 66,000 dalton (66 kDa) in chick embryo ganglia extracts. Treatment of intact ganglia with TPA for 30 min also specifically stimulated the phosphorylation of the same protein. When staurosporine, a potent inhibitor of protein kinase C, was present during TPA treatment, both neurite outgrowth and the phosphorylation of the 66-kDa protein were blocked. Biochemical analysis of the phosphorylated 66-kDa protein indicated that (1) phosphorylation was only in serine residue, (2) the pI value was 4.5, (3) after V8 protease digestion, two phosphorylated peptide fragments, 6.0 and 7.5 kDa in size, were produced, and (4) it cross-reacted with an antiserum raised against a 66-kDa neurofilament subunit from rat spinal cord. These results suggest that early activation of protein kinase C and the phosphorylation of the 66-kDa protein may be involved in neuritogenesis.

Alkaloids↗
PubMed1992

Dual effects of endothelin-1 on neurite outgrowth induced by 12-O-tetradecanoylphorbol-13-acetate.

The vasoactive peptide endothelin-1 (ET-1) was found to bind to a single class of binding sites in chick embryonic sensory ganglia with a Kd of 67 +/- 5 pM. Treatment of ganglia explants with 100 pM ET-1 did not affect neuronal development, but when added together with 12-O-tetradecanoylphorbol-13-acetate (TPA) a synergistic stimulation of neurite outgrowth was observed. In contrast, 10 nM ET-1 inhibited TPA-induced neurite outgrowth. Both the stimulatory and inhibitory effects were not blocked by nifedipine, a Ca2+ channel blocker. These results suggest that ET-1 can modulate the process of neurite outgrowth and its effects are not dependent on voltage-gated Ca2+ channels.

Animals↗
PubMed1992

Transport of the thyroid hormones across the feline gut wall.

Intestinal absorption of radioiothyroxine (T4*) and of radiotriiodothyronine (T3*) was studied in normal cats (n = 5 for T4* and n = 6 for T3*). Absorption was localized by a series of studies comparing the time-activity data for plasma and fecal T4* or T3* radioactivity after i.v. administration with data obtained in the same cats after administration by the oral, jejunal, midileal, and cecal routes. Data were analyzed using a multicompartmental model to account for longitudinal gut transit, metabolic loss, and reversible and irreversible binding, as well as absorption. The relative importance of the gut as a site for T4* or T3* residence at steady state was determined from T4* (n = 6) and T3* (n = 3) content of gut wall and contents at the end of tracer infusion to steady state. Secretion of T4* and T3* from the general pool into the various parts of the gut was calculated from the steady-state data by fitting them to the model using its steady-state parameters. Secretion parameters were adjusted in this fitting process, which established the rate and sites of T4* and T3* secretion into the gut. Overall, feline absorption of T4* and T3* is low compared with absorption in human subjects. Gentamicin treatment enhanced T3* absorption, but general wasting (weight loss associated with time under study) had no effect on either T4* or T3* absorption. The most important site for absorption of both T4* and T3* is the jejunum-upper ileum bowel segment. However, when the mass of gut wall in each segment is taken into account, absorption rate is highest at the duodenum and decreases distally. Secretion of both T4* and T3* is most active into the duodenum, presumably largely through the bile. In addition, there is active secretion of both T4* and T3* into the ileum and of T4* into the colon. These studies indicate that T4* and T3* absorption and secretion balance to make the gut an important locale for both hormones. Because of the cat's relatively low T4 and T3 absorption rates, much of the gut contents are destined for excretion. However, an active secretion-reabsorption loop for both T4* and T3* is present.

Administration, Oral↗
PubMed1991

Isolation and characterization of Escherichia coli K-12 mutants lacking both 2-acyl-glycerophosphoethanolamine acyltransferase and acyl-acyl carrier protein synthetase activity.

2-Acyl-glycerophosphoethanolamine (2-acyl-GPE) acyltransferase and acyl-acyl carrier protein (acyl-ACP) synthetase are thought to be dual catalytic activities of a single inner membrane enzyme. A filter disc replica print method for the detection of acyl-ACP synthetase activity by colony fluorography was used to screen a mutagenized population of cells for acyl-ACP synthetase mutants (aas). All aas mutants lacked both acyl-ACP synthetase and 2-acyl-GPE acyltransferase activities in vitro. There was no detectable acyl-CoA-independent incorporation of exogenous fatty acids into phosphatidylethanolamine or the major outer membrane lipoprotein in aas mutants. Exogenous lysophospholipid uptake and acylation was also lacking in aas mutants. Lipoprotein acylation by phospholipids synthesized by the de novo biosynthetic pathway was not affected in aas mutants showing that this gene product was not directly involved in lipoprotein biogenesis. The aas mutants had an altered membrane phospholipid composition and accumulated both 2-acyl-GPE and acylphosphatidylglycerol. Acylphosphatidylglycerol accumulation was due to the transacylase activity of lysophospholipase L2 (the pldB gene product) since aas pldB double mutants accumulated 2-acyl-GPE, but not acylphosphatidylglycerol. The aas allele was mapped to 61 min of the Escherichia coli chromosome, and the deduced gene order in this region was thyA-aas-lysA. The biochemical, physiological, and genetic analyses of aas mutants support the conclusion that 2-acyl-GPE acyltransferase and acyl-ACP synthetase are two activities of the same protein and confirm that this enzyme system participates in membrane phospholipid turnover and governs the acyl-CoA independent incorporation of exogenous fatty acids and lysophospholipids into the membrane.

Acylation↗
PubMed1991

Does cholesterol screening result in negative labeling effects? Results of the Massachusetts Model Systems for Blood Cholesterol Screening Project.

Several previous studies that looked at the effects of labeling individuals as hypertensive found increases in psychosocial distress, diminished feelings of well-being, or absenteeism. Other studies found no such effects. Thus far, similar studies relating to labeling for high blood cholesterol levels have not been published. The Massachusetts Model Systems for Blood Cholesterol Screening Project investigated whether labeling effects occurred as a result of the community-based screening, education, and referral programs it conducted in Worcester and Lowell. Nine questions concerning perceptions of physical and psychological well-being were asked on a questionnaire given to screening participants. The same questions were asked as part of a follow-up questionnaire given to all individuals identified as having high blood cholesterol levels at one of the screenings. Comparison of the baseline and follow-up results did not demonstrate significant overall negative effects among any age, sex, racial, income, or educational groups. On the contrary, responses to many of the questions revealed small but statistically significant improvements in perceptions of physical and psychological well-being. The absence of negative labeling effects may be attributable to the positive, supportive approach to participant counseling taken by the project.

Adult↗
PubMed1990

Risk stratification after percutaneous transluminal coronary angioplasty.

Approximately 20-30% of patients who undergo elective percutaneous transluminal coronary angioplasty (PTCA) require a second angioplasty within 12 months. A significant proportion of patients develop clinical cardiac events during the first year following the initial procedure. The present investigation was undertaken to establish a statistical model for predicting such events. The study group consisted of 100 patients who underwent elective PTCA at the University of Alberta Hospital. All patients were prescribed nifedipine (10 mg tid) and aspirin (325 mg daily) in addition to other medications determined by the attending cardiologist. The patients were reviewed 10 weeks after the procedure and again at the end of 1 year. The follow-up was completed on 96 patients. Within the first year, forty-five experienced cardiac events (1 death, 5 myocardial infarctions, 4 bypass surgeries, 22 repeat PTCAs). These events occurred in 29 patients. An additional 16 patients experienced significant anginal symptoms. A statistical model based upon the patients' perception of symptoms immediately after the procedure, history of hypertension, vessel subjected to PTCA, ejection fraction pre-PTCA, and occurrence of intimal dissection during PTCA was used to identify patients likely to develop cardiac events. Overall, the model classified 72% of the patients (with and without events). Such a statistical model could be used to identify patients who should be subjected to an enhanced degree of cardiologic surveillance in a rehabilitation program.

Aged↗
PubMed1990

Immunoglobulin E and circulating immune complexes in endolymphatic hydrops.

Levels of circulating immune complexes (CICs) in 59 patients with Meniere's disease and total serum immunoglobulin E (IgE) levels in a subgroup of 42 of the 59 were determined quantitatively for possible abnormalities of humoral immunity. Significant differences in average IgE levels between the 42 patients with Meniere's disease and 18 normal control subjects were not determined; however, five (11.9%) of the 42 patients were found to have obviously raised IgE levels. Elevated CIC levels were found in 19 (32.2%) of the 59 patients with Meniere's disease and in one (2.3%) of the 43 control subjects. This difference was statistically significant. The possible mechanisms of immune-mediated endolymphatic hydrops are discussed.

Adult↗
PubMed1989

Induction of neurite outgrowth from chick embryonic ganglia explants by activators of protein kinase C.

Neurite outgrowth from chick embryonic sensory ganglia explants was induced by activators of protein kinase C and other compounds known to stimulate the hydrolysis of inositol phospholipids. The addition of diacylglycerols, phospholipase C and muscarine chloride to a defined growth medium promoted the outgrowth of dense neurites from ganglia explants which were morphologically distinct from those induced by the phorbol ester TPA. Moreover, these neurite-promoting agents did not enhance non-neuronal cell proliferation and were ineffective in the absence of insulin and/or progesterone.

Animals↗
PubMed1989

2-Acylglycerolphosphoethanolamine acyltransferase/acyl-acyl carrier protein synthetase is a membrane-associated acyl carrier protein binding protein.

Two enzymatic activities, 2-acylglycerolphosphoethanolamine (2-acyl-GPE) acyltransferase and acyl-acyl carrier protein (acyl-ACP) synthetase, were solubilized and purified from Escherichia coli membranes. Electrophoretic analysis of the final product of the purification procedure revealed a single protein species with an apparent molecular mass of 27 kilodaltons. The ratio of acyltransferase to synthetase activities remained the same throughout the purification scheme indicating that both activities were catalyzed by the same enzyme. 2-Acyl-GPE acyltransferase exhibited an apparent ACP Km of 64 nM under standard assay conditions that increased to 10 microM when the assay was conducted in the presence of 0.4 M LiCl. Acyl-ACP synthetase activity was not detected in the absence of 0.4 M LiCl, and the apparent ACP Km for this reaction was 16 microM. Direct evidence that ACP was a subunit of the acyltransferase/synthetase was obtained by the adsorption of both catalytic activities to an ACP-Sepharose affinity column and by the binding of [3H]ACP to the purified enzyme preparation. The apparent Km for acyl-ACP was 13 microM, and the rate of acyl transfer from this acyl donor was enhanced by the addition of 0.4 M LiCl indicating that the exchange of enzyme-bound ACP for acyl-ACP was a determinant factor in the rate of phosphatidylethanolamine formation from acyl-ACP. These data indicate that the 2-acyl-GPE acyltransferase and acyl-ACP synthetase reactions are catalyzed by the same membrane protein that possesses a high affinity binding site for soluble ACP.

Acyl Carrier Protein↗
PubMed1989

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on axonal elongation and fasciculation.

Ultrastructural examination of neurons treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) confirmed our previous finding that TPA promoted neurite differentiation. At the low concentration of 16 nM TPA, the outgrowth of long neurites was correlated with the increased appearance of membrane-filled varicosities and filopodial extensions along the axons. In contrast, treatment with high concentrations of TPA (160 nM) produced dense outgrowths which were shorter in length and organized as thick fascicles. Increased neurite fasciculation appeared to result from the enhanced side-to-side interactions of neighboring neurites by a neural cell adhesion molecule. Axons within these fascicles were retracted and appeared congested with cytoskeletal and membranous components. Treatment with the antibody to the neural cell adhesion molecule defasciculated the thick outgrowths and permitted further axonal elongation.

Animals↗