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Biomedical subjects

B Hsu

Publications and source records attributed to B Hsu.

At least 19 recordsLinked to original sources
PubMed2003

Optical systems for in vivo molecular imaging of cancer.

Progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. In this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. We describe initial results obtained using optically active contrast agents to image the expression of three well known molecular signatures of neoplasia: including over expression of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs), and oncoproteins associated with human papillomavirus (HPV) infection. At the same time, we are developing inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time. These real-time, portable, inexpensive systems can provide tools to characterize the molecular features of cancer in vivo.

Biomarkers, Tumor↗
PubMed2001

Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency.

BLyS (also called BAFF, TALL-1, THANK, and zTNF4), a TNF superfamily member, binds two receptors, TACI and BCMA, and regulates humoral immune responses [1-7]. These two receptors also bind APRIL [7-10], another TNF superfamily member. The results from TACI(-/-) and BCMA(-/-) mice suggest the existence of additional receptor(s) for BLyS. The TACI knockout gives the paradoxical result of B cells being hyperresponsive, suggesting an inhibitory role for this receptor [11, 12], while BCMA null mice have no discernable phenotype [13]. Here we report the identification of a third BLyS receptor (BR3; BLyS receptor 3). This receptor is unique in that, in contrast to TACI and BCMA, BR3 only binds BLyS. Treatment of antigen-challenged mice with BR3-Fc inhibited antibody production, indicating an essential role for BLyS, but not APRIL, in this response. A critical role for BR3 in B cell ontogeny is underscored by our data showing that the BR3 gene had been inactivated by a discrete, approximately 4.7 kb gene insertion event that disrupted the 3' end of the BR3 gene in A/WySnJ mice, which lack peripheral B cells.

Amino Acid Sequence↗
PubMed2001

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey.

Antithymocyte globulin (ATG) is accepted as a treatment option for steroid-refractory acute graft-versus-host disease (GVHD). We conducted an international survey to determine how steroid refractoriness is defined and how ATG is used in clinical practice. Responses were received from 153 centers in 36 countries. The most common threshold steroid dose to define steroid refractoriness was 2 mg/kg/day (67% of respondents), and the median duration of treatment before failure was declared varied from 3 to 5.5 days, depending on whether failure was defined as 'progressed', 'not improved' or 'not resolved'. The threshold corticosteroid dose was significantly higher in pediatric centers than in adult or combined programs (P = 0.003). ATG was used routinely for treatment of steroid-refractory GVHD by 67% of the respondents. Horse ATG was used more frequently than rabbit ATG overall (50% vs 24%, P < 0.001), and predominance of horse ATG was most evident in the western hemisphere, in small- to medium-sized centers, and in pediatric centers. A wide variety of dose schedules for both drugs was reported. We conclude that there is some degree of variation in the definition of steroid refractoriness, especially between pediatric and nonpediatric programs, and no consensus has emerged in identifying the optimal ATG dose schedule in this setting.

Acute Disease↗
PubMed2001

Effect of sandblasting on the bond strength of the bondable molar tube bracket.

This study examined the effect of surface treatment with sandblasting on bracket bonding strength. Extracted human tooth, base metal alloy and porcelain surfaces were treated with sandblasting. The bracket bonding strengths of sandblasted surfaces were evaluated and compared with the controls and etched enamel surfaces. Morphological observation of the treatment surfaces and the failure sites was conducted. Statistical analysis included one-way analysis of variance (ANOVA) and a Scheffe's F-test at the 95% confidence level was performed. The results indicated that mean bond strength values ranged from 3.6 MPa (the untreated control) to 20.4 MPa for the etched enamel surface. No statistically significant differences were determined among the etched enamel, sandblasted metal and sandblasted porcelain surfaces (P > 0.05). Most debonding specimens failed at either the resin-tooth interface or within the adhesive. In conclusion, sandblasting the metal and porcelain surfaces obtained a bracket bond strength comparable with that with the etched enamel surface.

Acid Etching, Dental↗
PubMed1999

Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor.

Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin alpha. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin alpha. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1(-) GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export.

Amino Acid Sequence↗
PubMed1997

Autoimmune hemolytic anemia, primary adrenal insufficiency, and the antiphospholipid syndrome.

Autoimmune hemolytic anemia and adrenal insufficiency are rarely associated with the antiphospholipid antibody syndrome. A 49-year-old woman with a history of deep venous thrombosis and recurrent miscarriages was found to have active autoimmune hemolytic anemia after being admitted to the hospital for cholelithiasis. The patient was treated with corticosteroids and underwent laparoscopic cholecystectomy 1 month later. Two weeks after surgery she had acute adrenal insufficiency. Activated partial thromboplastin time was prolonged, and antiphospholipid antibodies were detected in significant titer. Her illness responded well to corticosteroid therapy. Her direct Coombs' test remained positive. It appears that the antiphospholipid antibody syndrome contributed to the development of venous thrombosis, recurrent miscarriages, autoimmune hemolytic anemia, adrenal insufficiency, and indirectly, pigment stone cholelithiasis in this patient.

Abortion, Habitual↗
PubMed1996

Recurrent substernal nodular goiter: incidence and management.

BACKGROUND: Surgery for recurrent multinodular goiter is associated with an increased risk of complications. When recurrence occurs in a substernal location, difficulties associated with surgical removal may be even more significant. METHODS: Information relating to indications for surgery, procedure performed, pathologic findings, and surgical complications was obtained from a prospective thyroid surgery database maintained in our unit for the past 39 years. RESULTS: During the study period 234 patients underwent operation for retrosternal recurrence of a nodular goiter. In the majority of cases (51%) the indication for surgery was the presence of compressive symptoms. In only four cases was a sternal split required to remove substernal recurrence. Complications occurred in 35 patients, including four permanent recurrent laryngeal nerve palsies. No patient had permanent hypoparathyroidism. CONCLUSIONS: Surgery for recurrent substernal goiter, although technically demanding, can be performed with a minimum of morbidity if appropriate attention is paid to anatomy and embryology. A sternal split is only rarely required.

Adult↗
PubMed1995

Cell death regulation during multistep lymphomagenesis.

The three most common genetic abnormalities occurring in malignant lymphomas involve alterations resulting in the deregulated expression of the c-myc and bcl-2 oncogenes and the inactivation of the p53 tumor suppressor gene. Relevant strains of genetically engineered mice, including bcl-2-Ig and E mu-myc transgenic mice and p53 knockout mice, have been used to prospectively examine the regulation of apoptotic cell death by these genes, individually and in combination, and their contribution to in vivo lymphomagenesis. The potential importance of the therapeutic induction of apoptosis is discussed.

Animals↗
PubMed1995

Evidence that c-myc mediated apoptosis does not require wild-type p53 during lymphomagenesis.

Deregulation of c-myc, frequently implicated in oncogenesis, is associated with increased cell proliferation and also cell death. Similarly, the p53 tumor suppressor gene commonly mutated in human tumors, is known to induce apoptosis or cell cycle arrest in its wild-type conformation. Genetically altered mice simultaneously overexpressing c-myc and possessing a disrupted p53 gene were used to investigate whether c-myc mediated apoptosis requires wild-type p53. The accelerated development of malignant lymphomas in these mice was found to be a consequence of enhanced proliferation and not reduced apoptosis resulting from the synergistic effect of c-myc overexpression and p53 inactivation.

Alleles↗
PubMed1995

The functional basis of c-myc and bcl-2 complementation during multistep lymphomagenesis in vivo.

Oncogenes are known to be deregulated by chromosomal translocations occurring at high frequency in specific malignancies. Among the most well characterized of these are c-myc, associated with the t(8;14) in Burkitt's lymphomas, and bcl-2, associated with the t(14;18) in follicular lymphomas. In addition to their role in regulating rates of proliferation, it is known that oncogenes and tumor suppressor genes can also regulate rates of apoptotic cell death. The contribution of c-myc and bcl-2 to the regulation of cell death during lymphomagenesis in vivo is assessed using bcl-2-Ig and emu-myc trangenic mice and bcl-2/myc hybrid transgenic mice. Translocations between the endogenous c-myc gene and immunoglobulin loci, e.g., t(12;15), are common in lymphomas arising in the bcl-2-Ig mice. Furthermore, bcl-2/c-myc double transgenic mice exhibit accelerated lymphomagenesis, indicating cooperation between these two oncogenes. Genetic complementation of c-myc and bcl-2 during lymphomagenesis resulted from the suppression of c-myc-associated apoptosis. Other genes are likely involved in regulating cell death during multistep lymphomagenesis.

Animals↗
PubMed1994

Hepatitis, HIV, and the dermatologist: a risk review.

The practice of dermatology has always carried with it the risk of patient-acquired infection. This review covers health risks associated with the care of HIV-infected patients and patients who are chronic carriers of hepatitis B or C virus, protection options to reduce exposure, and protocols should exposure occur. Hepatitis B continues to be a major risk to health care workers, killing approximately 200 per year. In contrast, as of 1990, only 327 total health care personnel had acquired HIV, with no deaths reported. Data are lacking regarding hepatitis C, but it appears to be an increasing concern. Needlesticks are the most common form of occupational transmission, with an infectivity rate of 30% for hepatitis B, 3% for hepatitis C, and 0.3% for HIV. Universal precautions are the cornerstones of safety. Hepatitis B vaccination, zidovudine prophylaxis, and hepatitis C therapy are discussed as postexposure recommendations are reviewed.

Canada↗
PubMed1994

Gender differences in sexual fantasy and behavior in a college population: a ten-year replication.

This report is a replication of a study conducted 10 years ago by Person et al., investigating gender differences in sexual behaviors and fantasies in a college population. We found that men continue to fantasize more than women, but the gender differences have narrowed. Recent sexual experiences of our population show a trend toward an increase in gender differences, and there is a greater correlation between sexual fantasy and experiences in women than in men. As in Person's study, we did not find that men had more aggressive/sadistic fantasies than women.

Adult↗
PubMed1994

Evidence that p53 and bcl-2 are regulators of a common cell death pathway important for in vivo lymphomagenesis.

Multistep lymphomagenesis involves the deregulation of oncogenes and inactivation of tumor suppressor genes resulting in altered rates of proliferation as well as apoptotic cell death in tumor cells. The contribution of bcl-2 and p53 to the regulation of cell death during lymphomagenesis is assessed using bcl-2-1g, p53 'knock-out' (p53 KO), and p53 KO/bcl-2 hybrid mice. PCR-SSCP and DNA sequence analysis demonstrated that p53 somatic mutations are uncommon in lymphomas arising in bcl-2-Ig transgenic mice. Reduction in tumor latency was not observed in p53 KO/bcl-2 hybrid mice compared to p53 KO mice. Furthermore, overexpressed bcl-2 suppressed wild-type p53 associated apoptosis following gamma-radiation. These findings indicate that bcl-2 and p53 serve a suppressor and effector function, respectively, of a common cell death pathway. These findings also suggest that p53 somatic mutations provide no selective advantage during in vivo multistep lymphomagenesis in the context of bcl-2 gene deregulation.

Animals↗
PubMed1993

The bcl-2 oncogene: apoptosis and neoplasia.

Cloning of the t(14;18) translocation breakpoint resulted in the identification of a new putative oncogene, which mapped to 18q21, termed bcl-2. The t(14;18) resulted in inappropriately high levels of bcl-2 expression in follicular lymphoma. Prospective studies using mice transgenic for a human bcl-2-immunoglobulin minigene, intended to recreate the molecular features of the t(14;18), demonstrated that bcl-2 gene deregulation was oncogenic. Interestingly, overexpression of bcl-2 showed no demonstrable influence on rates of cellular proliferation. Rather, bcl-2 was found to extend cellular viability by blocking apoptosis. Recent studies with other oncogenes and tumor suppressor genes, such as c-myc and p53, have demonstrated that the deregulation of apoptosis may be of general significance in the development of multiple types of cancer and appears to be a critical event during multistep carcinogenesis. The selective induction of apoptosis in tumor cell populations is now being considered in the design of novel therapeutic interventions.

Animals↗
PubMed1992

The roles of macrophage (M phi) and PGE-2 in postburn immunosuppression.

Postburn immunosuppression in mice with full skin thickness burns was assessed after Con A stimulation of splenic lymphocytes. The immunosuppression was detected within 24 h of injury and was maximal 3-7 days later. Such lymphocyte proliferation was enhanced by depletion of adherent cells (M phi) in burned mice and could be depressed in normal mice by injection of these adherent cells from burned mice. These results suggest the presence of M phi s with a suppressor function. No difference in spontaneous blastogenic transformation (SBT) of spleen cells between the burned and normal mice was found, but after removal of the M phi s the SBT of spleen cells of burned mice became significantly elevated. Hence both M phi and lymphocytes in mouse spleen cells were activated after severe thermal injury.

Animals↗
PubMed1990

Mutational analysis of the Escherichia coli glpFK region with Tn5 mutagenesis and the polymerase chain reaction.

Transposon Tn5 mutagenesis of the Escherichia coli chromosome was used to isolate 21 independent insertion mutations conferring an altered colony color phenotype on MacConkey-glycerol plates. The polymerase chain reaction was used to map 16 of these Tn5 insertions within the glpFK region at 88 min. The most polar Tn5 insertion was shown by nucleotide sequencing to be in the proposed glpF open reading frame. The data suggest that the glpF and glpK genes are in an operon with a bent DNA segment (BENT-6) involved in transcriptional regulation of this operon.

Aquaporins↗
PubMed1984

Mechanism of melphalan crosslink enhancement by misonidazole pretreatment.

Sensitization of Chinese hamster ovary cells to melphalan (L-PAM) toxicity by prior treatment with misonidazole (MISO, 5 mM, 2 hr, hypoxic conditions, 37 degrees C) is associated with increased levels of DNA crosslinks believed to be the critical lesion for bifunctional alkylating agent toxicity. Enhanced L-PAM crosslinking of DNA could occur by a variety of mechanisms in MISO-pretreated cells including: (1) increased transport or binding of L-PAM, (2) decreased repair of L-PAM monoadducts which would allow more time for their conversion to crosslinks, (3) decreased crosslink repair (unhooking of one arm), or (4) chemical modification of the DNA structure, presumably by bound MISO derivatives, such that crosslink formation is facilitated. Previous studies have eliminated mechanisms (1) and (3). Mechanism (4) was investigated by following MISO-pretreatments of whole cells with L-PAM treatments of the isolated DNA from these cells. This was accomplished by using a modification of the alkaline elution assay for DNA crosslink measurement in which a 1 hr treatment with L-PAM (0-12 micrograms/ml) was inserted between the cell lysis steps and DNA elution procedure. Treatment of bare DNA with L-PAM modeled very well the crosslinking behavior in whole cells although it was somewhat more efficient (more crosslinks at a given L-PAM dose). In the presence of double stranded DNA and absence of repair systems during and after the L-PAM exposure, it was determined that MISO-pretreatments did not increase the crosslinking efficiency of L-PAM (mechanism [4] above). Inhibition of repair of L-PAM monoadducts (mechanism [2] above) still remains as a possible means for crosslink enhancement by MISO-pretreatment.

Animals↗