Biomedical subjects
Publications and source records attributed to C S Chu.
Similar to the Landauer electric dipole created around an impurity by the electric current, a spin polarized cloud of electrons can be induced by the intrinsic spin Hall effect near a spin independent elastic scatterer. It is shown that in the ballistic range around the impurity, such a cloud appears in the case of Rashba spin-orbit interaction, even though the bulk spin Hall current is absent.
The intrinsic spin Hall effect on spin accumulation and electric conductance in a diffusive regime of a 2D electron gas has been studied for a 2D strip of a finite width. It is shown that the spin polarization near the flanks of the strip, as well as the electric current in the longitudinal direction, exhibit damped oscillations as a function of the width and strength of the Dresselhaus spin-orbit interaction. Cubic terms of this interaction are crucial for spin accumulation near the edges. As expected, no effect on the spin accumulation and electric conductance have been found in case of Rashba spin-orbit interaction.
We propose a setup which allows us to couple the electron spin degree of freedom to the mechanical motions of a nanomechanical system not involving any of the ferromagnetic components. The proposed method employs the strain-induced spin-orbit interaction of electrons in narrow gap semiconductors. We have shown how this method can be used for detection and manipulation of the spin flow through a suspended rod in a nanomechanical device.
Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.
OBJECTIVE: To compare survival of ovarian cancer patients with and without a family history of breast or ovarian cancer who are known to be without mutations in BRCA1. METHODS: Patients with ovarian cancer were tested for germline mutations in BRCA1 by polymerase chain reaction amplification of DNA for single-strand conformation polymorphism and direct sequencing analysis to examine the 22 coding exons of BRCA1 in fresh and archived tumor specimens. Demographic and survival data were collected for statistical analysis. Survival data were calculated by the method of Kaplan and Meier and compared by the log-rank test. RESULTS: Of the 110 patients tested at our institution, 100 were noted to be negative for BRCA1 mutations. After exclusion of nonepithelial histologies, benign tumors, primary peritoneal carcinoma, and incomplete staging, 87 patients remained for analysis, of which 37 demonstrated a family history of breast or ovarian cancer. The two groups showed similar age at diagnosis, stage, grade, residual disease, and type of chemotherapy. Median actuarial survival was 75 months for those patients with a family history versus 70 months for those without (P = 0.73). Evaluation of patients with two or more relatives with breast or ovarian cancer also revealed no differences in survival. CONCLUSIONS: Family history of breast or ovarian cancer does not affect survival of patients with ovarian cancer in the absence of mutations in BRCA1. Previously described differences in survival among patients with BRCA1 mutations may be more related to genetic factors than to biases introduced by the presence of family history.
Although second-look laparotomy (SSL) has been used in the management of ovarian cancer for over three decades, its current clinical use is limited. On average, over 50% of patients with a clinical complete response are noted to have disease at the time of SLL, emphasizing our lack of accurate noninvasive methods for determining pathologic response. Although findings at SLL have some prognostic significance, there is no definitive evidence that those patients undergoing SLL have improved survival, and even 50% of patients with negative findings at SLL have recurrences. The lack of survival advantage for patients enduring SLL highlights the need to identify consistently effective salvage and consolidation regimens. Few published studies provide definitive evidence regarding efficacy of treatment. Prospective, randomized, controlled trials are needed to evaluate the various therapies available. In general, the performance of SLL should be confined to those patients enrolled in clinical trials.
PURPOSE: Evaluation of the healing and persistence of a meshed composite skin graft applied without immunosuppression. METHODS: The contraction of wounds grafted with 9:1 split-thickness autograft/1.5:1 allodermal mesh composite skin grafts (auto/allo MCSGs) was investigated. No immunosuppressive agent was applied. Male ACI rats and female Lewis rats reciprocally served as allodermis graft donors and recipients. Autograft/dermal autograft and allograft/dermal allograft MCSGs were the controls. RESULTS: AT 3 months after grafting, when epithelized auto/allo MCSG wounds were measured by computerized morphometric analysis, the silver nylon (SN) dressing group displayed less contraction than the Vaseline (petroleum jelly) dressing group (p < 0.003), and direct current treatment (SNDC) was more effective than SN (p < 0.005). The histologic structures of the hair follicles appear to confine the rejection process to the allogeneic follicles of the graft. The focal nature of the rejection process and the relatively low antigenicity of the dermal matrix allowed the survival of the allodermis layer. Although direct current significantly enhanced MCSG healing, SN and SNDC were not the immunosuppressive agents that were confirmed. CONCLUSION: This type of MCSG can heal without immunosuppressive treatment.
BACKGROUND: Application of direct current (DC) to a burn wound limits extension of the zone-of-stasis and reduces wound tissue edema. OBJECTIVE: To study the effects of DC on extravasation of plasma proteins after burn by using Evans blue (EB) as a marker of plasma albumin. MATERIALS AND METHODS: Male Sprague-Dawley rats with 20% total body surface area full-thickness scalds (100 degrees C/10 sec) were used as the experimental model. Burn wounds were treated with plain nylon, silver-nylon, silver-nylon and 40 microA DC, or no dressing. EB (30 mg/kg) was injected immediately or at variably delayed postburn (PB) times and accompanied by DC application at various time intervals PB. Tissue content of Evans blue was assessed at different times after injection of the dye or infliction of burn injury. RESULTS: Evans blue albumin (EBA) concentration in untreated burn wounds (307.7 microg/g tissue) was nine times greater than in unburned skin (36.5 microg/g tissue) at 48 hours PB. When animals received a DC and EB injection immediately PB, DC treatment reduced EBA concentration by 60% at any time point PB. When EB was injected immediately PB, or at variably delayed times PB, accompanied by DC immediately PB, or at variably delayed times PB, DC reduced EBA accumulation at all examined times PB by more the 50% (p < 0.001). CONCLUSION: EBA and edema fluid accumulation in burn wound change in concert after injury and show similar response to DC treatment.
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The dichotomy between the doses at which experimental measurements of genetic effects can be made and the doses to which people are exposed is often different by two or more orders of magnitude. This presents a significant problem when determining the effects of low doses of radiation or chemicals. The solution has usually involved extrapolating the data by curve-fitting or by applying theoretical considerations. Both approaches are unsatisfactory due to uncertainties of the assumptions used in each process. The alternative solution has been to increase the sample size enormously at the lower doses. This is impractical beyond a certain point due to the variation in the spontaneous frequency and the need to quadruple the sample size for a doubling of precision. The development of new methods for measuring stable genetic effects, however, permits a simple and effective approach to this problem: if the genetic events being detected have no effect on survival, i.e., are selectively neutral, then the effects of multiple independent treatments will be additive. If the independent treatments are identical, then the effect of each is easily calculated by dividing the total effect by the number of treatments. Here we report a limited test of this approach using mice. Chromosome aberrations induced in lymphocytes and Dlb-1 mutations induced in the small intestine were measured after daily doses of 0.64, 1.85 or 5.5 cGy 137Cs gamma rays administered for 21, 42 or 63 days. The dose response curve for chromosome translocations obtained in this way, combined with the data from single larger acute doses, shows no evidence for a threshold over a 500-fold dose range. Dlb-1 mutations were increased at each dose and time but the results do not permit reliable extrapolations. The results suggest that translocations might be useful for quantifying the effect of doses below 0.05 cGy and that the effect of dose rate and dose fractionation at much lower doses than reported here could be investigated.
BACKGROUND: The purpose of this study was to determine the optimum autoepidermal and allodermal expansion ratio of each component of a meshed composite skin graft (MCSG) that would lead to successful healing. METHODS: Male Sprague-Dawley rats were used as hosts of the MCSG and donors of autologous tissue. Male ACI rats were used as donors of allodermis. MCSGs with open meshed area (autoepidermal/allodermal) of 9:1/1.5:1, 9:1/3:1, 9:1/6:1, or 6:1/6:1 were applied to full-thickness skin defects and treated with a silver nylon dressing (SN) or SN with direct current (DC). Wound size, hair regrowth, and thickness of dermal layer were evaluated at 3 months. RESULTS: MCSGs of 9:1/1.5:1, 9:1/3:1, and 6:1/6:1 mesh ratios healed completely within 3 months with no difference in wound size between SN dressing groups or DC-treated groups. Application of DC reduced MCSG contraction and stimulated regrowth of hair. CONCLUSION: Fresh autoepidermis can be expanded 6:1 on a 6:1 allodermis or 9:1 on a 3:1 allodermis and achieve successful wound healing.
Limited data exist on the oral ecology of vegetarians. Hence the dental and periodontal status, and the oral prevalence of aerobic and facultatively anaerobic Gram-negative rods (AGNR) and yeasts, were studied in 36 semi-recluse, vegetarian, Buddhist monks and nuns in Hong Kong. The oral prevalence of AGNR and yeasts was 61.1% and 33.3%. There was no correlation between the prevalence of AGNR and/or yeasts and the incidence of carious or filled teeth and the health status of the periodontium. Rather, the results of this study combined with those of previous studies suggest that increasing age and the consumption of food prepared in communal kitchens might be more important contributory factors in the oral prevalence of AGNR than the nature of the diet itself or the health of the dentition and periodontium.
OBJECTIVE: To observe the effect of 4 and 40 microA direct current (DC) on edema formation after burn injury in rats. DESIGN, MATERIALS, AND METHODS: Silver-nylon wound dressings were used as either anodes (-) or cathodes (+) on 20% total body surface area full-thickness scalds in anesthetized male Sprague-Dawley rats. Untreated burned rats and rats treated with silver-nylon dressings without current were used as controls. MEASUREMENTS AND MAIN RESULTS: Immediately applied, continuous DC reduced burn edema by 17 to 48% at different times up to 48 hours postburn (p < 0.001). Neither reversal of electrode polarity nor change in current density had any significant effect on the results of treatment. Starting treatment during the first 8 hours postburn produced the least edema accumulation, but the reduction was significant even when DC was applied 36 hours afterburn. If started immediately after injury, treatment had to be continued a minimum of 8 hours to be most effective. CONCLUSIONS: Direct electric current has a beneficial effect in reducing wound edema after burn injury.
OBJECTIVE: To observe the effect of 40 microA direct current (DC) on plasma albumin extravasation after burn injury. DESIGN, MATERIALS, AND METHODS: Silver-nylon wound dressings were used as anodes (-) on anesthetized male Sprague-Dawley rats with 20% total body surface partial-thickness scald burns. Burned rats with no treatment, or treated with silver-nylon dressing without current, were used as controls. Quantitative analysis of fluorescein isothiocyanate (FITC)-albumin leakage and accumulation in the wound tissue was performed using confocal fluorescence microscopy. MEASUREMENTS AND MAIN RESULTS: In controls, the rate of albumin leakage was maximal at 1 hour postburn (PB) and then decreased, but remained higher than normal for 48 hours PB. The accumulation of FITC-albumin was maximal 4 to 6 hours PB and substantial for 48 hours. When DC was applied, leakage was reduced by 30 to 45% and approached normal control rates by 8 hours PB. FITC-albumin concentration peaked 4 hours PB, was 18 to 48% less then in burned control, and approached the level observed in unburned control by 18 hours PB. CONCLUSIONS: DC has a beneficial effect in reducing plasma protein extravasation after burn injury.
BACKGROUND: Cholecystitis is a frequently encountered clinical problem. What parameters are reliable in helping predict its severity? METHODS: One hundred and forty-nine cholecystectomized cases of cholecystitis were analysed of which 99 (95 calculous) cases were pathologically diagnosed as chronic cholecystitis and 50 acute (43 calculous) cholecystitis. Medical records were reviewed to determine the frequency of toxic signs. Sonographic findings (performed within three days prior to operation), and final pathological changes with respect to the thickness and echotexture of the gallbladder wall were compared. RESULTS: Of 99 chronic cholecystitis patients, 13 cases showed toxic signs. Sonography detected an abnormal wall in 64, but made a correct diagnosis in only 34 cases. A great discrepancy was found in wall thickness as measured by sonography and pathology. A discrepancy > or = 2mm was noted in 19 cases. Of 50 patients with acute cholecystitis (20 cases had complications, defined as severe acute cholecystitis), 31 cases (14 of the 20 severe acute cases) showed toxic signs. Sonographic findings demonstrated an abnormal wall in 46 cases (19 of the severe acute cases) and an accurate diagnosis in 28 cases (13 of the severe acute cases). A difference in the measurement of gallbladder wall thickness > or = 2mm was noted in 26 patients. CONCLUSIONS: Clinical toxic signs and sonographic findings could not offer sufficient information to quickly identify lifethreatening gallbladder diseases.
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OBJECTIVE: Observe the effect of silver-nylon (SN) dressing and direct electric current on healing of meshed autoepidermal/allodermal composite skin grafts (MCSGs) in allosensitized rats. MATERIALS AND METHODS: MCSGs were placed on experimental animals 28 to 30 days after placement of sensitizing allografts. MCSGs and control allografts were covered with either Vaseline gauze (VG) or SN; direct current, 40 microA, was applied for 5 days to some of the SN-dressed wounds (SNDCs). MEASUREMENTS AND MAIN RESULTS: Second set rejection of MCSG was not observed. SN- and SNDC-treated grafts showed expansion of the meshed autoepidermis with complete epithelialization within 3 weeks. VG-covered wounds developed areas of open granulation and were not completely epithelialized at 3 months. Both SN and SNDC reduced wound contraction when compared to VG (SN versus VG p < 0.02, SNDC versus VG p < 0.008). MCSG was found to be of low alloantigenicity in that it did not induce second set rejection of subsequent skin allograft. CONCLUSIONS: SN dressings enhanced survival of meshed composite skin grafts.
The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway epithelial cells. Quantification of CC10 gene expression in freshly isolated human proximal airway epithelial cells demonstrated very high mRNA levels, approximately fivefold greater than gamma-actin mRNA, and in situ hybridization localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis demonstrated that the human CC10 gene is comprised of three short exons separated by a long first and short second intron, and with a 5' flanking region typical of a regulated gene. Three Alu repeats were observed in intron 1 and one in intron 2. Two polymorphic regions within the introns were identified. First, a microsatellite was localized 5' to the third Alu repeat in intron 1 with a variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71. Second, in 3% of the 168 chromosomes examined, there was the insertion of a human-specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between markers D11S16 and D11S97, a region recently linked to atopy and to the beta-subunit of the high-affinity immunoglobulin E receptor. The observations in the present study of high-level expression of the CC10 gene in the epithelium of conducting airways and a subchromosomal localization of the gene to a region potentially linked to inflammatory airway disease, together with the reported anti-inflammatory and immune-modulating properties of the protein, suggest the CC10 gene product may be important in modulating inflammation within the airways. If so, the highly heterozygous microsatellite described in the present study should facilitate analysis of a possible linkage of the CC10 gene with an inherited susceptibility to asthma.