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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 271 records · Page 15Linked to original sources

From diversity to unity. The classification of mental disorders in 21st-century China.

Psychiatric disease constructs represent social constructs and genuine states of distress that have biopsychosocial sources. As such, they have social uses peculiar to the social groups in which they are created and legitimized. This is as true in the United States as in the rest of the world. The DSM schema, for instance, is so organized that every possible mental condition is listed as a disease to legitimate remuneration to practitioners from private medical insurance and government programs. This particular social use may be irrelevant to other societies where health care is financed differently. The CCMD-3 system represents an attempt at global unification and preservation of features that are salient for local application. Compared with its previous editions, noticeable changes have been made to render it in tune with international usage. This remarkable speed of adaptation speaks to the global flows of information technology and China's openness under rapid economic reform. It also demonstrates that the middle-aged cohort of more pragmatic Chinese psychiatric leaders who headed the CCMD-3 task force are now less vulnerable to the domination of the most senior generation of Chinese psychiatrists. Having been trained in the Russian system of psychiatry and gone through the various periods of national shame that traumatized China, they used to be very cautious about adopting foreign technology in general. This is why much less harmonization with the ICD-10 occurred with the CCMD-2-R, when the responsible task force was, for better or worse, dominated by these senior psychiatrists. Nonetheless, as Stengel and Sartorius remarked, an international classification must not aim to oust or replace regional classifications that serve valuable functions in the local contexts. No single classificatory system, Kirmayer submits, will suffice for all purposes--the correct diagnostic scheme is the one that accomplishes its explicit pragmatic aim by addressing the relevant level of description. The particular additions (e.g., travelling psychosis, culture-related mental disorders), deletions (e.g., depressive neurosis, pathologic gambling, avoidant and borderline personality disorders), retentions (e.g., unipolar mania, neurosis, hysteria, homosexuality), and epistemologic variations (e.g., somatoform disorder, neurasthenia) of diagnostic categories reflect exactly this simultaneous need to globalize and to take account of the changing reality of illness in contemporary China. Stengel advised that "no psychiatric classification can help being partly etiological and partly symptomatological, because these are the criteria by which psychiatrists distinguish mental disorders from each other." To an extent, the CCMD-3 is a critique of certain nosologic assumptions of Western psychiatry, such as the feasibility of a neo-Kraepelinian taxonomy grounded exclusively in symptomatology across all diagnostic categories, and the validity of syndromic architectures based on a firm adherence to the mind-body dichotomy. From this angle of vision, local systems of classification such as the CCMD-3 may offer an opportunity for needed reflections by North American psychiatrists who have simply taken the DSM-IV schema for granted. Sartorius reckoned that a classification is a way of seeing the world at a point in time. A deep study of the CCMD-3 is thus an avenue for achieving an understanding of the contemporary Chinese mind and the social realities in China. The remarkable diversity of China at present, namely, a Communist Party dominated state socialist political structure but the most rapidly growing capitalist economy in the world, guarantees that Chinese people's social and moral experience of illness will continue to change. The study of such culture-specific categories as travelling psychosis, neurasthenia, qigong-induced mental disorder, and dysfunctional homosexuality sheds light on the larger sociomoral processes and destabilizing changes in subjectivity that are occurring in this most populous country in the world.

China↗

Reverse osmosis filtration for space mission wastewater: membrane properties and operating conditions.

Reverse osmosis (RO) is a compact process that has potential for the removal of ionic and organic pollutants for recycling space mission wastewater. Seven candidate RO membranes were compared using a batch stirred cell to determine the membrane flux and the solute rejection for synthetic space mission wastewaters. Even though the urea molecule is larger than ions such as Na+, Cl-, and NH4+, the rejection of urea is lower. This indicates that the chemical interaction between solutes and the membrane is more important than the size exclusion effect. Low pressure reverse osmosis (LPRO) membranes appear to be most desirable because of their high permeate flux and rejection. Solute rejection is dependent on the shear rate, indicating the importance of concentration polarization. A simple transport model based on the solution-diffusion model incorporating concentration polarization is used to interpret the experimental results and predict rejection over a range of operating conditions. Grant numbers: NAG 9-1053.

Creatine↗

Clinical spectrum of reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy syndrome is a recently recognized disorder with characteristic radiologic findings that mainly involve the white/gray matter of the parieto-occipital lobes. This complex syndrome is associated with cyclosporine A therapy or a variety of other conditions in which blood pressure rises acutely. Twelve patients from a variety of conditions who met the diagnostic criteria for this syndrome were studied. Interestingly, three of these patients had intra-abdominal neurogenic tumors, which have rarely been reported. Initial cranial magnetic resonance imaging scans revealed fairly symmetric areas of increased T(2) signal involving both white and gray matter of parieto-occipital lobes in the majority of the patients. However, the lesions were often located outside the parieto-occipital regions. Four patients had occipital region magnetic resonance spectroscopy during the acute phase, which revealed high lactate peak and normal N-acetyl aspartate/creatine and choline peaks. With appropriate treatment, most patients recovered from this syndrome and experienced almost complete resolution of brain lesions on follow-up magnetic resonance imaging. One patient, however, continued to have small residual hemosiderin deposits on a follow-up magnetic resonance imaging with neurologic sequellae. In conclusion, a better understanding of this complex syndrome may obviate unnecessary investigations and allow management of the associated problems in prompt and appropriate ways.

Adolescent↗

The correlation of MHC haplotype and development of Behçet's disease-like symptoms induced by herpes simplex virus in several inbred mouse strains.

It has been postulated that human leukocyte antigen (HLA)-B51 is associated with Behçet's disease. In previous study, we induced Behçet's disease-like symptoms in ICR mice inoculated with herpes simplex virus. In this study, several inbred mouse strains -- B10.BR (H-2k), B10.RIII (H-2r), C57BL/6 (H-2b), C3H/He (H-2k), Balb/c (H-2d) -- which had different types of major histocompatibility complex (MHC), were inoculated with herpes simplex virus type 1 (KOS strain) in order to demonstrate the role of histocompatibility antigen in the development of Behçet's disease-like symptoms. Behçet's disease-like symptoms developed in 40-50% of B10.BR, B10.RIII and C57BL/6 strains, but in only 2% of C3H/He and Balb/c. B10.BR and C3H/He strains had a common haplotype (H-2k) but the rate of manifestation was different. So, we conclude that MHC is not directly correlated with development of Behçet's disease-like symptoms in the animal model of herpes simplex virus induced Behçet's disease-like symptoms.

Animals↗

Synthesis and phosphodiesterase 5 inhibitory activity of new 5-phenyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one derivatives containing an N-acylamido group phenyl ring.

New sildenafil analogues with an N-acylamido group at the 5'-position of the phenyl ring, 6a--e, were prepared from the readily available starting compound 2 in four straightforward steps. Enzyme assays demonstrated that all the target compounds 6a-e showed higher PDE5 inhibitory activities than sildenafil. It was observed that the PDE5 inhibitory activity was enhanced as the chain length of R group increased, but introduction of the branched alkyl groups such as isopropyl (6d) and cyclohexyl (6e) resulted in the drop of potency compared with 6c. In particular the N-butyrylamido derivative 6c exhibited the highest PDE5 inhibitory activity, and was about 6-fold more potent than sildenafil. However, all the compounds exhibited somewhat weak selectivity (1--3-fold) over PDE6, indicating that the compounds 6a--e have intrinsically lower selectivity than sildenafil.

Phosphodiesterase Inhibitors↗

Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.

3',5'-Cyclic-GMP Phosphodiesterases↗

The truncated cytoplasmic tail of HLA-G serves a quality-control function in post-ER compartments.

In contrast to the current model of MHC class I trafficking, which predicts that once a MHC class I molecule leaves the ER, it moves to the cell surface by bulk flow, we show that HLA-G that is loaded with suboptimal peptides is retrieved from post-ER compartments to the ER. Loading of HLA-G with high-affinity peptides abrogates this retrieval due to the lack of binding affinity to coatomer. Moreover, the loss of the endocytosis motif in the truncated cytoplasmic tail results in the prolonged half-life of HLA-G on the cell surface. Our findings reveal that surface expression of HLA-G can be further regulated in post-ER compartments and that the truncated cytoplasmic tail plays a critical role in such quality-control mechanisms.

Amino Acid Motifs↗

Review of evaluation tools used to assess the impact of nutrition education on dietary intake and quality, weight management practices, and physical activity of low-income audiences.

Nutrition education programs and social marketing campaigns frequently focus on low-income audiences with the goal of improving dietary intake and quality, weight management practices, and physical activity. The impact of nutrition education can be assessed by measuring change in relation to any or all of these broad variables. Unfortunately, little information is available concerning the reliability, validity, and sensitivity to change of measures used to assess these constructs with low-income audiences of adults and adolescents. This article reviews the literature and discusses the types of available measures that have been used and evaluated for the above audiences. It describes specific measures used to assess total diet, consumption of food groups from the Food Guide Pyramid, and behaviors related to weight management and physical activity. Overall, this review suggests that there is a critical need for additional development and evaluation of dietary quality measurement tools for low-income and minority audiences.

Body Weight↗

Determinants on tmRNA for initiating efficient and precise trans-translation: some mutations upstream of the tag-encoding sequence of Escherichia coli tmRNA shift the initiation point of trans-translation in vitro.

tmRNA facilitates a novel translation, trans-translation, in which a ribosome can switch between translation of a truncated mRNA and the tmRNA's tag sequence. The mechanism underlying resumption of translation at a definite position is not known. In the present study, the effects of mutations around the initiation point of the tag-encoding sequence of Escherichia coli tmRNA on the efficiency and the frame of tag translation were assessed by measuring the incorporations of several amino acids into in vitro poly (U)-dependent tag-peptide synthesis. One-nucleotide insertions within the tag-encoding region did not shift the frame of tag translation. Any 1-nt deletion within the span of -5 to -1, but not at -6, made the frame of tag translation heterologous. Positions at which a single base substitution caused a decrease of trans-translation efficiency were concentrated within the span of -4 to -2. In particular, an A-4 to C-4 mutation seriously damaged the trans-translation, although this mutant retained normal aminoacylation and ribosome-binding abilities. A possible stem and loop structure around this region was not required for transtranslation. It was concluded that the tag translation requires the primary sequence encompassing -6 to +11, in which the central 3 nt, A-4, G-3, and U-2, play an essential role. It was also found that several base substitutions within the span of -6 to -1 extensively shifted the tag-initiation point by -1.

Acylation↗

Low-density lipoprotein-antioxidant constituents of Saururus chinensis.

A new diarylbutane lignan, saururin A (1), and a known 8-O-4'-type neolignan, machilin D (2), were isolated from a total methanol extract of the underground parts of Saururus chinensis. The structures of 1 and 2 were elucidated by spectroscopic data analysis. Compounds 1, 2, and virolin (3) (the methyl ether of 2) exhibited significant low-density lipoprotein (LDL)-antioxidant activity in the thiobarbituric acid-reactive substance (TBARS) assay with IC(50) values of 8.5, 2.9, and 4.3 microM, respectively.

Anti-Inflammatory Agents, Non-Steroidal↗

Hemodilution - an overview of current canadian practices.

Background. Transplant teams evaluate potential organ and tissue donors to exclude donation of tissues at risk for disease transmission. Standards dictate that serological tests be performed on every donor to assess the presence of transmissible diseases including: Human Immunodeficiency Virus 1 & 2, Human T Lymphotropic Virus 1 & 2, Hepatitis C, Hepatitis B surface Antigen, Hepatitis B core Antibody and Syphilis. A limitation of serological testing is the risk of false negative results due to the dilution of the serum. Hemodilution results from the transfusion of fluids (blood products, colloids and/or crystalloid). Confidence in the accuracy and sensitivity of donor serology testing is of utmost importance to ensure the provision of safe organs and tissues for transplantation.Methods. In order to determine the preferred and validated methodology for determining hemodilution, if any; and to determine the level of hemodilution that jeopardizes serologic test results, we reviewed the literature and current testing practices. Tissue banks throughout Canada as well as accrediting bodies were contacted regarding the hemodilution algorithm they utilize.Results. In the absence of a pretransfusion sample, hemodilution calculations are the prevalent methodology for assessing sensitivity of serology testing. A literature search and personal communications provided no documentation on the validation of any hemodilution algorithm or evidence that 50% hemodilution is an acceptable level for accurate serology testing.Conclusion. A validation of hemodilution algorithms and the acceptable or unacceptable rate of hemodilution is required. The utilization of a validated algorithm should be mandated in standards to ensure continuity of practice by all transplantation centres. If validation cannot be obtained, alternative methodologies for serology testing should be investigated.

Journal Article↗

Hyaluronate receptors mediating glioma cell migration and proliferation.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

Antibodies, Monoclonal↗

Carboxyalkylated histidine is a pH-dependent product of pegylation with SC-PEG.

PURPOSE: Pegylation of therapeutic protein usually results in a mixture of monopegylated proteins with differing sites of modification. With rh-interferon-alpha2A pegylation, we have found that this heterogeneity includes two classes of pegylation site chemistry, the relative proportions of which can be adjusted by reaction pH. METHODS: The effect of pegylation reaction pH on the relative proportion of three peaks produced was investigated. Products were purified and characterized by peptide mapping, chemical stability to neutral hydroxylamine, and biologic activity. RESULTS: Reactions at basic pH levels produced a mixture of products pegylated at lysine residues as has been observed elsewhere. However, the dominant product of reactions at mildly acidic levels of pH showed distinct chemistry and higher cytopathic effect activity. The primary site of modification at this pH was His34. We developed a quantitative assay using sensitivity to neutral hydroxylamine to measure the proportion of urethane bonds involving carboxyalkylated histidines. This assay showed that histidine was pegylated preferentially at low pH levels with another protein, rh-Interleukin-10. CONCLUSIONS: Reaction pH can be used to select the preferred pegylation site chemistry.

Alkylation↗

Spontaneous amyloidosis in twelve chimpanzees, Pan troglodytes.

Spontaneous amyloidosis was diagnosed in 11 male and 1 female chimpanzees and confirmed histologically and immunohistochemically. The chimpanzees were > or = 15 years of age when first diagnosed and averaged 22.4 years of age. The average survival time after diagnosis of systemic amyloidosis was 1.86 years with a standard deviation of 4.06 years (n = 7). The chimpanzees with amyloidosis were asymptomatic except for hepatomegaly, which became more detectable with age. Significant increases in clinical chemistry values, as compared with referenced normals and established normals, of blood urea nitrogen (BUN), asparate aminotransferase (AST), gamma-glutamyltransferase (GGT), globulin, total protein, creatinine phosphokinase (CPK), sedimentation rate, and triglycerides were found in animals 7 years of age or older with amyloidosis. These serum chemistry values, while increased in chimpanzees with amyloidosis, were generally within normal limits. Immunohistochemistry for both amyloid A protein and amyloid P component-labeled extracellular amyloid in all chimpanzees with amyloidosis was determined. Amyloid was deposited primarily in the liver. Amyloidosis in the chimpanzee is a chronic, intractable, progressive, fatal disease, and appears to be similar to secondary amy loidosis in other species.

Amyloidosis↗

Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients.

In a retrospective single center study, we examined the outcome of induced GVHD in leukemia patients relapsing after allogeneic BMT. Thirty-three adult patients with leukemia (15 AML, 3 ALL, and 15 CML) persisting or relapsing 1-36 months (median, 6) after allogeneic BMT underwent various immune manipulations and consequently developed acute and/or chronic GVHD at our center. Immunotherapies to elicit GVHD comprised chemotherapy followed by PBSC (n = 18), non-myeloablative transplant (n = 2), PBL followed by IFN-alpha (n = 5), PBL alone (n = 3), abrupt cessation of CsA (n = 3), and CsA withdrawal combined with IFN-alpha (n = 2). Twenty-four (72.7%) patients obtained a remission including complete hematological or cytogenetic remission, respectively, for acute leukemias or CML. Overall survival of patients, estimated at 3 years using the Kaplan-Meier method, was 33.9% (95% CI, 20-52%). Twelve patients including two patients with ALL remain in complete hematological (n = 5) or cytogenetic remission (n = 7) 3-93 months (median 12) after achieving remission. Twelve (63.2%) of 19 dead patients died due to treatment-related toxicities; five patients from acute GVHD, three from GVHD followed by infections and four from infections. By multivariate Cox analysis, only chronic GVHD resulted in a higher probability of disease-free survival (P = 0.026). Eight patients who had both acute GVHD < or = grade I and chronic GVHD are all alive without leukemia. We conclude that acute GVHD is associated with considerable toxicity while chronic GVHD plays a role in retaining remission in leukemia relapsing after allogeneic BMT.

Adolescent↗

Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice.

A substrain of the senescence-accelerated mouse (SAM), the SAMP1 mouse, is an animal model for accelerated senescence including the age-related acceleration of both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells. In the present study, we examine whether the accelerated presbycusis can be prevented by allogeneic BMT. Young SAMP1 (H-2(k)) mice were irradiated with 9 Gy and then reconstituted with bone marrow cells from normal BALB/c (H-2(d)) mice. Allogeneic BMT was found to prevent the development of immunological dysfunction, hearing loss, and apoptosis of spinal ganglion cells in SAMP1 mice. These findings indicate that some types of accelerated presbycusis do not result from defects in the cochlea, but do from defects in the hematopoietic stem cells (HSC) and immunocompetent cells derived from the HSC. If this is the case, either allogeneic BMT, which replaces abnormal HSC with normal HSC and reconstructs a normal immune system in the recipients, or autologous BMT using genetically modified bone marrow cells, could become a new strategy for the treatment of presbycusis.

Age Factors↗

The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation.

Pro-inflammatory (IL-6, TNFalpha and IL-8) and anti-inflammatory (IL-10) cytokines were determined in weekly samples from 52 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IL-6 increased immediately after transplant peaking at week +3, but IL-8 concentrations were elevated only during week +1. After a slight decrease in week +1, TNF-alpha significantly increased from week +2 and peaked at week +3, whereas, IL-10 values started to rise in week +2 and peaked during week +4. IL-6 and TNF-alpha were positively correlated from week +2 to week +4, and IL-6 levels at week +1 were related with fever and severe stomatitis. Serum levels of IL-6 at week +1 and IL-10 at week +4 were significantly higher in patients with early transplant-related complications, such as fever, severe stomatitis or acute GVHD > or = overall grade II than in those without the complications. We conclude that a high serum IL-6 level at week +1 may be an early predictor of transplant-related complications and that it seems to trigger pro- and anti-inflammatory cytokine release. Kinetic patterns of IL-6 and IL-10 were more exaggerated in those with complications after HSCT.

Acute Disease↗