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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 937 records · Page 52Linked to original sources

Heterotypic adherence between human B-lymphoblastic and pre-B-lymphoblastic cells and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha mediates only the early phase of the heterotypic adhesion.

Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM-1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow.

Antibodies, Monoclonal↗

Homooligopeptides composed of hydrophobic amino acid residues interact in a specific manner by taking alpha-helix or beta-structure toward lipid bilayers.

In order to investigate the role of each amino acid residue in determining the secondary structure of the transmembrane segment of membrane proteins in a lipid bilayer, we made a conformational analysis by CD for lipid-soluble homooligopeptides, benzyloxycarbonyl-(Z-)Aaan-OEt (n = 5 - 7), composed of Ala, Leu, Val, and Phe, in three media of trifluoroethanol, sodium dodecyl sulfate micelle, and phospholipid liposomes. The lipid-peptide interaction was also studied through the observation of bilayer phase transition by differential scanning calorimetry (DSC). The CD studies showed that peptides except for Phe oligomers are present as a mainly random structure in trifluoroethanol, as a mixture of alpha-helix, beta-sheet, beta-turn, and/or random in micelles above the critical micellization concentration and preferably as an extended structure of alpha-helical or beta-structure in dipalmitoyl-D,L-alpha-phosphatidylcholine (DPPC) liposomes of gel state. That the beta-structural content of Val oligomers in lipid bilayers is much higher than that in micelles and the oligopeptides of Leu (n = 7) and Ala (n = 6) can take an alpha-helical structure with one to two turns in lipid bilayers despite their short chain lengths indicates that lipid bilayers can stabilize the extended structures of both alpha-helical and beta-structures of the peptides. The DSC study for bilayer phase transition of DPPC/peptide mixtures showed that the Leu oligomer virtually affects neither the temperature nor the enthalpy of the transition, while Val and Ala oligomers slightly reduce the transition enthalpy without altering the transition temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗

Interaction of mastoparan-B from venom of a hornet in Taiwan with phospholipid bilayers and its antimicrobial activity.

Mastoparan B (MP-B), an amphiphilic alpha-helical peptide newly isolated from the hornet Vespa basalis, was studied in comparison with mastoparan (MP), in terms of interaction with the phospholipid bilayer and of hemolytic and antimicrobial activity. The amphiphilic structure of MP-B has more hydrophilic amino acid residues in the hydrophilic surface than that of MP. Although each peptide had a considerably different effect on the interaction with lipid bilayers (e.g., their conformation in the presence of acidic and of neutral lipids and dye-release ability from the encapsulated liposomes), on the whole the interaction mode was similar. MP-B caused a change in the shape of erythrocytes from normal discoid to a crenated form (named echinocytes). MP exhibited strong activity against gram-positive bacteria but not against gram-negative ones. Contrary to this, MP-B showed both strong activity against gram-positive bacteria and potent activity against gram-negative bacteria. Whereas both peptides have almost the same residues on the hydrophobic side, the difference in the hydrophilic surface area on the molecules seems to lead to the subtle change in its interaction with membranes, resulting in the alteration of biological activity.

Amino Acid Sequence↗

Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression.

Group I Burkitt lymphoma (BL) lines retaining the original BL tumor cell phenotype are unable to present endogenously expressed antigens to HLA class I-restricted cytotoxic T cells (CTL) but can be recognized if the relevant HLA class I/peptide epitope complex is reconstituted at the cell surface by exogenous addition of synthetic target peptide. Endogenous antigen-processing function is restored in BL lines that have undergone Epstein-Barr virus (EBV)-induced drift in culture to the group III phenotype typically displayed by EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA-class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)-2, lmp-7 and delta, although the mb-1 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter-associated proteins (Tap), with down-regulation of Tap-1 and Tap-2 in 8/8 and 7/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap-deficient T2 processing-mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus-encoded latent membrane protein-1 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up-regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen-processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon-gamma treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen-processing function of BL cells, and suggest that the accessibility of other EBV-associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Transplantation of reproductive organs.

A historical review of the literature concerning replantation and transplantation of reproductive organs has included studies from this laboratory, using rats, over the past 25 years. From the basic observation of ischemic and traumatic injury due to the transplantation, syngeneic testicle transplants, resulting in a partner's impregnation and histological restoration of the testicles, led to human testicular transplantation. As to the ovarian transplants, granulosa-theca cell tumors may transform into malignancies if followed for a prolonged period as intrasplenic ovaries, and high doses (15 to 20 mg/kg b.w.) of azathioprine can produce such malignant tumors in a shorter period. By caval-portal shunt, ovarian hormones enter directly into the portal blood stream and no typical granulosa-theca cell tumors were produced, owing to the fact that the liver cannot degrade all the hormones secreted by both ovaries. While en-bloc vagino-utero-ovarian transplantation in the rat is possible, no impregnation has been yet achieved. Finally, it is hypothesized that those who have acquired microsurgical techniques and have a full understanding of the anatomy of the reproductive system will not only be able to perform replantation of the penis, but also will be capable of allogeneic transplantation of genital organs, whether ethically approved or not, and sooner than one may think. In such cases a penile part may be obtained at a sex-change surgery or from a cadaveric donor, similar to other vital organ transplantation practices.

Animals↗

The immunostimulatory compound 7-allyl-8-oxoguanosine (loxoribine) induces a distinct subset of murine cytokines.

C8- and N7, C8-substituted guanine ribonucleosides comprise a class of molecules with potent immunostimulatory activity for a variety of humoral and cellular immune responses. Although it has been suggested that the immunostimulatory activity may be partially mediated by cytokine production, to date there has been no systematic evaluation of the spectrum of cytokines elicited by these nucleosides. In this study, we examine the cytokines produced by murine spleen cells in response to the di-substituted guanosine analog loxoribine (7-allyl-8-oxoguanosine). First, the levels of cytokine mRNA in spleens from vehicle- or loxoribine-treated mice were compared using PCR analysis with a panel of cytokine-specific primers. Enhancement of IL-1 alpha, TNF-alpha, TNF-beta, IL-6, IFN-alpha, and IFN-gamma mRNA was seen in the spleens of loxoribine-treated mice. IL-12 mRNA responses were more complex, with an increase in the p40 chain and a decrease in the p35 chain. In contrast, no increase was seen for mRNA levels of IL-2, IL-3, IL-4, IL-5, IL-7, or GM-CSF. ELISA assays on the supernatants of loxoribine-treated spleen cells demonstrated that IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were all produced in a dose-dependent fashion with TNF-alpha produced first, followed by IL-6 and IFN-gamma, and last by IL-1 alpha. IFN-alpha beta activity rose as quickly as TNF-alpha, leveling off at 8 to 12 hr, and was supplanted by a later-occurring surge of IFN-gamma production. IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were also detected in the sera of mice injected with loxoribine. When antibodies against the relevant cytokines were tested, only anti-IFN-alpha beta inhibited NK activity or lymphocyte proliferation and, in both cases, activity was partially restored by the addition of exogenous IFN-alpha beta. Taken together, these data indicate that loxoribine induces the production of a selective cohort of cytokines all of which have been shown to have immunostimulatory activity. However, only IFN-alpha beta appears to play a role in the enhancement of NK activity and lymphocyte proliferation.

Animals↗

Terminal differentiation-dependent alteration in the expression of translation elongation factor-1 alpha and its sister gene, S1, in neurons.

Elongation factor-1 alpha (EF-1 alpha) is a highly conserved, abundantly expressed protein that functions in peptide elongation during mRNA translation. Mammalian species contain a second EF-1 alpha gene, S1, whose expression is limited to brain, heart, and skeletal muscle. Such tissue specificity in S1 gene expression led us to hypothesize that this specialized member of the EF-1 alpha family is possibly essential to terminally differentiated, long-lived cells such as neurons, cardiomyocytes, and myocytes. We report here that during development, EF-1 alpha mRNA levels remain unchanged in S1-negative tissues, but sharply decrease in S1-positive tissues. RNase protection as well as tissue distribution analyses of the S1 message suggest that down-regulation of EF-1 alpha expression coincides well with that of S1 up-regulation during postnatal development. Analysis of primary cultures of the rat neonatal cerebral cortex cells has shown that S1 gene expression is indeed restricted to neurons only, whereas nonneuronal cell types such as astrocytes and microglia are S1-negative. EF-1 alpha mRNA on the other hand was detected in all three cell types, namely, neurons, astrocytes, and microglia. This report confirms the terminal differentiation-dependent expression of the S1 gene in neurons of the cerebral cortex.

Animals↗

Rat heart-aorta cluster transplantation: a novel model to study transplant rejection.

The purpose of this study was to develop a microsurgical cluster model of heart plus entire thoracic aorta transplantation and to compare it to the isolated model of heart transplantation as a tool to study transplant rejection. Thirty-six syngeneic (DA x DA and Lew x Lew) and allogeneic (DA x PVG and DA x Lew) cluster heart-aorta transplants were compared to 43 syngeneic and allogeneic isolated heart grafts. Graft survival, recipient survival and histological data on myocardial and aortic tissues were assessed. There was no statistically significant difference in graft survival between the two models studied (P > 0.05). In the cluster transplants, the aortic component was spared the severity of acute rejection noted for the myocardial counterpart. In conclusion, the results demonstrated that the cluster model was technically feasible and highly reproducible. Additionally, it was possible to apply this model to the study of experimental allograft rejection using novel immunosuppressants. The success of the cluster model in strongly mismatched transplant strain combinations underscores its potential for application in slower rejection combinations, making it particularly suited for chronic rejection studies. The inherent capacity for sampling a broader range of vessel sizes in one animal makes the cluster model more suitable than the isolated models of aorta or heart for application to experimental protocols.

Animals↗

Rethinking neurasthenia: the illness concepts of shenjing shuairuo among Chinese undergraduates in Hong Kong.

Neurasthenia is both a Western disease construct and a popular Chinese illness concept (shenjing shuairuo, SJSR). Using a self-report questionnaire, we examined 148 Hong Kong Chinese undergraduates' concept of its epidemiology, symptomatology, etiology and treatment. Notwithstanding that fatigue is the sine qua non of neurasthenia in Western nosology, subjects believed that SJSR was compatible with a diversity of symptoms which fell, on factor analysis, into the "neurotic," "psychotic," "somatic" and "dysfunctional" subgroups. Contrary to the popular portrayal of SJSR as a physical or chronic fatigue disorder, the most common perceived symptoms were anxiety, insomnia, depression and fright. Logically, psychological etiology and remedy were highly emphasized. The perceived high prevalence, non-aggressive nature and symptomatic diversity of SJSR attested to the notion that it might camouflage and destigmatize psychiatric labels of insanity. The contextual study of neurasthenia illustrates how in its search for legitimacy an originally Western concept adapts, transforms, and acquires distinctive local meanings in a non-Western culture.

Adolescent↗

Classifying change with the Sickness Impact Profile for Nursing Homes (SIP-NH).

The aim of this cohort study was to evaluate the concordance of the Sickness Impact Profile for Nursing Homes (SIP-NH) and Sickness Impact Profile (SIP) in classifying change. Subjects consisted of 194 consecutive long-stay nursing home residents at one academic department of the V.A. and in 8 community proprietary nursing homes in San Antonio, Texas. They were to have more than 3 months residency; to be > or = 61 years; and to be dependent in at least 2 ADLs with an MMSE score of > or = 15. Subjects were administered a 128-item SIP and a reduced 66-item SIP-NH at baseline and 4, 8, and 12-month follow-up. At each follow-up, subjects were classified into 3 mutually exclusive change categories using a change score of > or = 5 points. Concordance of the classification of subjects by the SIP-NH and SIP was evaluated. The misclassification rate as well as its direction was also assessed. Both instruments classified a little over one-quarter of the subjects as better, over a third as being unchanged, and another third as being worse at the four-month follow-up. More subjects were classified as worse by both instruments at 8 and 12 months. All kappas ranged from 0.52 to 0.78, indicating good to excellent agreement. Overall, the SIP-NH characterized persons as changed more often than the SIP with no systematic directional bias. In conclusion, the SIP-NH was concordant with the SIP in classifying change in subjects. However, we cannot say which of the two is better for detecting change. Future research must focus on defining a change score which has clinical meaning, and evaluate responsiveness to change.

Activities of Daily Living↗

Self-starvation in context: towards a culturally sensitive understanding of anorexia nervosa.

Extreme forms of self-starvation can be traced across time and place, and may be construed using a variety of explanatory models. Curiously, the prevailing biomedical definition of anorexia nervosa has assigned primacy to the exclusive use of 'fat phobia' by the affected subjects to justify their diminished food intake. This paper assembles evidence to show that this culturally constructed version of fat phobic anorexia nervosa has neglected the full metaphorical significance of self-starvation and, when applied in a cross-cultural context, may constitute a category fallacy. By delegitimizing other rationales for non-eating and thereby barring subjective expressions, this regnant interpretive strategy may obscure clinicians' understanding of patients' lived experience, and even jeopardize their treatment. Nonetheless, it is a relatively simple task to attune the extant diagnostic criteria to a polythetic approach which will avert cultural parochialism in psychiatric theory and practice. As a corollary of the archival and ethnocultural study of extreme self-starvation, there is, contrary to epistemological assumptions embedded in the biomedical culture of contemporary psychiatry, no 'core psychopathology' of anorexia nervosa.

Adult↗

Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots.

Fibrinolysis is accelerated in vitro in an ultrasound field, and externally applied high frequency ultrasound also accelerates thrombolysis in animal models. Although the mechanism of this effect is not known, ultrasound does not cause mechanical disruption of clots but rather accelerates enzymatic fibrinolysis. To determine if accelerated fibrinolysis could be related to increased transport of enzyme into clot, we have examined the effect of insonification on the distribution of plasminogen activator between clot and surrounding fluid in vitro. Plasma clots were overlayed with plasma containing 125I-radiolabeled, active-site-blocked recombinant tissue plasminogen activator (rt-PA) and incubated in the presence of 1-MHz ultrasound at 4 W/cm2 or in the absence of ultrasound. The rate of uptake of rt-PA was significantly faster in the presence of ultrasound, reaching 15.5 +/- 1.4% at 4 h compared to 8.2 +/- 1.0% in the absence of ultrasound (p < 0.0001). Similarly, ultrasound increased transport of enzyme from the clot into the surrounding fluid. To determine the effect of ultrasound on the spatial distribution of enzyme, plasma clots were overlayed with plasma containing radiolabeled rt-PA and incubated in the presence or absence of ultrasound. The clots were then snap-frozen, and the radioactivity in serial cryotome sections was determined. Exposure to ultrasound altered the rt-PA distribution, resulting in significantly deeper penetration of rt-PA into the clots. We conclude that exposure to ultrasound increases uptake of rt-PA into clots and also results in deeper penetration. These effects of ultrasound on enzyme transport may contribute to the accelerated fibrinolysis observed in an ultrasound field.

Biological Transport↗

Physical factors involved in stress-wave-induced cell injury: the effect of stress gradient.

We have studied the biological effects of ablation-induced stress waves in vitro. Mouse breast sarcoma cells (EMT-6) were exposed to stress waves that differed only in rise time. Two assays were used to determine cell injury: incorporation of tritiated thymidine (viability assay), and transmission electron microscopy (morphology assay). We present evidence that the rise time of stress waves can significantly modify cell viability and that cell injury correlates better with the stress gradient than peak stress.

Animals↗

Repair of posterior base of a maxillary complete denture by use of a cast of stone and resilient material.

A method to repair a fractured complete denture and simultaneously augment deficient borders or correct an inadequate posterior palatal seal is described. Corrections were made intraorally with modeling compound and an elastomeric impression material. A resilient impression material was used to block out the undercuts in the denture, and repair was accomplished with visible light-cured resin or an autopolymerizing repair resin. This technique simplifies the laboratory procedures and thereby permits the return of the denture to the patient at the same visit.

Acrylic Resins↗