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Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 307 records · Page 17Linked to original sources
PubMed1996

Facilitation of DLA-incompatible marrow grafts by donor-specific serum transferrin?

Studies in mice have shown that donor-specific plasma transferrin (TF) given to the recipient in the peritransplant period facilitates engraftment of marrow from histoincompatible donors. Dogs given 920 cGy of total body irradiation (TBI) and infused with marrow from an unrelated major histocompatibility complex (DLA) different donor generally fail to engraft; only approximately 20% of dogs achieve sustained engraftment. We have now investigated in this model whether the infusion of donor-specific plasma TF would facilitate engraftment. Ten dogs were given TBI, followed at 23 h by an intravenous dose of TF, at 24 h by marrow from the same donor, and another dose of TF at 48 h; six dogs also received postgrafting methotrexate (MTX). Seven dogs (three of four without MTX, four of six with MTX) had sustained engraftment, and three dogs failed to engraft. A single dog given third-party TF failed to engraft. Among five dogs not given TF two achieved sustained engraftment. This pilot study suggests that donor-specific TF facilitates engraftment of DLA-incompatible marrow. Further studies are warranted.

Animals↗
PubMed1996

Induction of helical conformation in all beta-sheet proteins by trifluoroethanol.

The effect of 2,2,2-Trifluoroethanol (TFE) on the structure of five all beta-sheet proteins, isolated from the venom of the Taiwan cobra (Naja naja atra), is studied. In all the toxins used, it is observed that significant amount of alpha-helix is induced at higher concentrations of TFE. In all these proteins, the induction of helical conformation and disruption of the tertiary structure seem to occur simultaneously. The structural transitions induced by TFE in reduced and denatured protein appear to be different from those observed in the native protein(s). In our opinion, the findings reported herein could have significant implications on research in the area of protein folding.

Circular Dichroism↗
PubMed1996

Internal packing conditions and fluctuations of amino acid residues in globular proteins.

In order to investigate the environmental conditions of amino acid residues in protein molecules, four kinds of packing studies (atomic, geometric, hydrophobic and hydration) were formulated and tested on two proteins; bovine pancreatic trypsin inhibitor (BPTI) and bovine pancreatic ribonuclease S (RNase S). The inter-relationship of these packings on the fluctuations of amino acid residues was analysed by comparing the packing results with the dynamical studies, such as the root-mean-square-deviation values of atomic displacements obtained from the trajectories of molecular dynamics simulation, temperature factor information from crystal structures and residue fluctuations in proteins from continuum model. These analyses yield information about the most fluctuating and most stabilizing residue sites. Comparison of the results obtained by these methods indicate a good agreement, specifying an inverse correlation between the residue packing and fluctuations. This kind of study is helpful in identifying the specific residue sites such as nucleation, receptor binding and antigenic determining sites which in a way indirectly correlates with the functional residues in protein molecules.

Amino Acids↗
PubMed1996

Automated scoring of micronuclei in binucleated human lymphocytes.

Manual and automatic scoring of micronuclei (MN) in binucleated human lymphocytes (BNC) were compared after irradiation of whole blood samples. The blood samples were irradiated with X-ray doses (1, 2 or 3 Gy) and stained with Giemsa. The preparation technique was optimized in such a way that acceptable conditions (cell density, contrast) were obtained for both scoring procedures. To estimate the quality of automatic micronucleus detection, two researchers who had different experience in scoring MN (6 months and 5 years) analysed the samples independently from each other. Automatic scoring was carried out with a digital image analysis system and the recognition procedure was divided into two parts. The BNC positions were detected with low microscope magnification (100x), and the recognition of micronuclei within the cytoplasm of the classified BNC was carried out at high magnification (630x). A fuzzy logic classification system as well as two different segmentation steps (preclassification and postclassification) made it possible that about 94% of all automatically recognized BNC were classified correctly). On the other hand, the classification system was optimized in such a way that false positive decisions were minimized (95% of automatically recognized micronuclei were classified correctly). Failure to recognize micronuclei (8.5%-25% false negatives) was mainly due to extremely small micronuclei, poor contrast with respect to the cytoplasm, and aggregation of micronuclei especially at higher doses.

Automation↗
PubMed1996

A novel monoclonal antibody, L1A3, is directed to the functional site of the alpha v integrin subunit.

We have generated a monoclonal antibody (MAb) L1A3 directed to the alpha v integrin subunit as shown by competitive binding with other anti-alpha v-specific MAbs and immunodepletion. MAb L1A3 is a function-blocking antibody inhibiting cell adhesion to the extracellular matrix proteins, fibronectin and vitronectin. Adherence to vitronectin of all cells studied including normal dermal microvascular endothelial cells and three tumor cell lines was inhibited in the presence of MAb L1A3. However, the contribution of the alpha v integrin subunit in mediating adhesion to fibronectin was dependent on the cell line, as indicated by differences in the inhibition of cell adhesion with MAb L1A3 and alpha 5 beta 1 integrin subunit blocking MAb P1D6. Glioma U251.3 cell adhesion to fibronectin was blocked by either MAb L1A3 or MAb P1D6 while fibrosarcoma HT1080 cells were blocked with MAb P1D6 only. Tumor cell migration mediated by vitronectin and fibronectin is blocked by MAb L1A3 in the two-dimensional spheroid outgrowth assay. Microvascular endothelial cell transwell membrane migration onto the fibronectin was also blocked by MAb L1A3. Comparison of the integrins involved in U251.3 cell migration on fibronectin or tenascin using a panel of integrin blocking MAbs including MAb L1A3 showed that only a subset of integrins participating in cell adhesion is essential for cell migration and these integrins appear to be ligand specific. Fibronectin-mediated tumor cell migration was critically dependent on alpha v integrins as shown by L1A3 blocking of migration while the beta 1 integrins were absolutely necessary for tenascin-mediated cell migration.

Animals↗
PubMed1996

Mechanical malfunction of the Leksell Gamma knife during patient treatment.

During the course of a patient treatment with a North American U-type gamma unit, the remote hydraulic valve controlling the direction of couch motion failed to change state. The couch, helmet and patient remained in treatment position after the expiration of treatment time for one of the target shots. No unusual equipment warning indications had been observed prior to the malfunction. The gamma unit was new, having been used to treat approximately 20 patients since it had begun to be used clinically 11 weeks previously. This specific situation was not addressed in our posted Emergency Procedures, which dealt explicitly with loss of electrical power, and loss of hydraulic pressure. In the present case, the hydraulic gauges indicated full pressure. After attempts to disengage the patient remotely proved unsuccessful, personnel entered the room. The table clutch at the foot of the couch was operated to disengage the couch/helmet assembly from its docked position. While this was not mentioned in our emergency procedures, the act had the effect of causing the cobalt-60 sources to be misaligned with the collimator apertures, thereby immediately terminating the patient treatment. This also had the unanticipated effect of substantially reducing radiation leakage exposure rate next to the couch near the tunnel opening. The patient was released from the helmet trunnions using a manufacturer-supplied long-handled special Allen key. The key was used conventionally, to release the trunnion locking mechanism, and also unconventionally to force a separation of a trunnion from the docking slot on the patient head frame. The patient was then removed from the tunnel by sliding out the pad on which she was lying. Anesthesiology personnel accompanied the patient out of the room. The unit functioned properly upon the replacement of the valve by manufacturer service personnel the next day. The patient returned for completion of treatment 1 week later. There were only minor changes to the overall patient dosimetry as a result of the malfunction. Personnel exposures were very low. The malfunction was reported to State authorities, who conducted an investigation, that was in turn followed up by an investigation by the Nuclear Regulatory Commission.

Dose-Response Relationship, Radiation↗
PubMed1996

Decreasing disability in the 21st century: the future effects of controlling six fatal and nonfatal conditions.

OBJECTIVES: This study assessed the effects of reducing fatal and nonfatal health conditions on the number of functionally limited older Americans in the coming decades. METHODS: Data from the 1990 census and the Longitudinal Study of Aging were used to project the number of functionally limited older Americans from 2001 to 2049, assuming 1% biennial reductions in five conditions that shorten life expectancy (coronary artery disease, stroke, cancer, diabetes, and confusion) and one condition that decreases functional ability (arthritis). RESULTS: Decreasing the prevalence of arthritis by 1% every 2 years would lead to a much greater reduction in functional limitation between 2001 and 2049 (4 million person-years) than would decreasing any of the other conditions by the same amount. Decreases in two fatal conditions (cancer and coronary artery disease) would lead to increases in functional limitation (0.9 and 0.1 million person-years, respectively). CONCLUSIONS: Advances against common nonfatal disabling conditions would be more effective than advances against fatal conditions in blunting the large increase in the functionally limited older population anticipated in the 21st century.

Aged↗
PubMed1996

Measurement of differences in pO2 in response to perfluorocarbon/carbogen in FSa and NFSa murine fibrosarcomas with low-frequency electron paramagnetic resonance oximetry.

We have used very low-frequency electron paramagnetic resonance (EPR) oximetry to measure the change in oxygen concentration (delta pO2) due to change in breathing atmosphere in FSa and NFSa fibrosarcomas implanted in the legs of C3H mice infused with perfluoro-octylbromine (PFOB). Measurements in each tumor were made before and after the administration of the high-density (47% v/v) perfluorocarbon PFOB, perflubron (Alliance Pharmaceutical Corporation, San Diego, CA). Measurements in each tumor were also made, after the administration of the PFOB, both before (PFOB/air) and after the administration of carbogen (95% O2 + 5% CO2, PFOB/carbogen). Large changes (delta p02) relative to PFOB/air oxygenation were seen with the administration of PFOB/carbogen. No significant difference in oxygen concentration was seen between air-breathing mice with and without PFOB. The mean delta pO2 for FSa tumors was 13 +/- 6 torr, while the mean for NFSa fibrosarcomas was 28 +/- 7 torr. There were such large intertumor differences that the trend toward a smaller change in the more hypoxic FSa tumors was not significant (P = 0.13). This paper describes a novel method of measuring differences in oxygenation in tumor tissues. The results of such measurements indicate large differences in pO2 response to different breathing atmospheres in PFOB-infused tumors of similar histology. The intertumor delta pO2 differences may correlate with differences in radiation response.

Animals↗
PubMed1996

Tacrolimus (FK506) and methotrexate regimens to prevent graft-versus-host disease after unrelated dog leukocyte antigen (DLA) nonidentical marrow transplantation.

We previously reported an synergism between methotrexate and tacrolimus (FK506) in preventing graft-versus-host disease (GVHD) in dogs given DLA-nonidentical unrelated marrow grafts after 9.2 Gy of total body irradiation (TBI). Methotrexate was given at 0.4 mg/kg i.v. on days 1, 3, 6 and 11 and FK506 at 0.15 mg/kg/day i.m. on days 0-8 and 0.5 mg/kg/day orally on days 9-90. Half of the dogs became long-term survivors. A major toxicity was gastrointestinal, and 25% of dogs died with intussusception. The current study addresses the problem of intussusception by making changes in drug doses used. In one group of dogs, FK506 was reduced to 0.075 mg/kg i.m. on days 1-8, while methotrexate was administered per original schedule. In a second group, methotrexate was reduced to a single dose on day 7, while FK506 was either administered per the original or reduced-dose schedule. None of the 17 current dogs developed intussusception, however, all but two dogs died with GVHD (n = 12) or graft failure (n = 3). Only two dogs survived after transient GVHD. Results show that there is little room for maneuvering FK506 or methotrexate doses, and hopes of reducing gastrointestinal toxicity by dose modifications while retaining the ability to prevent GVHD were not fulfilled.

Animals↗
PubMed1996

Effect of organic acids in the prevention of aggregation on rapid refolding of proteins.

The effect of organic acids on the aggregation of protein(s) during rapid refolding is studied. Using egg white lysozyme, it is observed that acetic acid not only prevents aggregation, but also aids the protein to refold back to its native, biologically active state. In contrast, formic acid, propionic acid and butyric acid fail to exhibit this property. Using circular dichroism spectroscopy it has been found that an 'aggregation-insensitive' partially folded intermediate state is induced in 0.35M acetic acid.

Acetic Acid↗
PubMed1996

Delay of radiation-induced decline and recovery of hematopoiesis following treatment with anti-HLA-DR antibody.

A dose of 200 cGy of total-body irradiation (TBI) is nonlethal in dogs: Following a granulocyte nadir in the third week post-TBI, peripheral blood cell counts recover to normal values by about 5 weeks. In the context of studies on a potential role of major histocompatibility (MHC) class II antigens in the regulation of stress hematopoiesis, we tested the effect of anti-MHC class II monoclonal antibodies (mAbs) on hematologic recovery after TBI. Thirteen dogs were given 200 cGy of TBI not followed by marrow infusion. Five received no additional treatment (concurrent controls) and eight were given daily intravenous (IV) injections of anti-class II mAbs H81.9 (anti-HLA-DR; n = 6) or B1F6 (anti-HLA-DR and -DP; n = 2) at 0.6 (n = 4) or 1.2 mg/kg/d (n = 4) on days 0-4 (n = 7) or days 0-9 (n = 1). One control dog died early from an intercurrent infection and four recovered uneventfully. Dogs given mAbs after TBI showed significantly different granulocyte and platelet kinetics. The granulocyte nadir was lower (p = 0.09) and was reached later (p = 0.005), the duration of neutropenia was longer (p = 0.08), and recovery occurred later (p = 0.02) than among controls. Similarly the platelet nadir was lower (p = 0.05), thrombocytopenia lasted longer (p = 0.02), and recovery occurred later (p = 0.02) than among controls. Four of eight mAb-treated dogs died with marrow aplasia. We propose that following irradiation, HLA-DR mediated signals result in terminal differentiation in more mature hematopoietic precursors but interfere with replication or differentiation in early hematopoietic precursors. These observations suggest a role for MHC class II molecules in the regulation of stress hematopoiesis.

Animals↗
PubMed1996

[Hypergonadotropic secondary amenorrhea: clinical analysis of 126 cases].

OBJECTIVE: To study the etiology and early diagnosis of hypergonadotropic amenorrhea and to explore the appropriate treatment for preserving their reproductive function. METHODS: 126 cases of secondary amenorrhea with serum follicular stimulating hormone (FSH) levels > or = 40 IU/I, were analysed. Their clinical manifestations, karyotypes, ovarian morphology and histology, reproductive hormone assays, and responses to estrogen therapy and ovulation induction were studied. RESULTS: 6 cases presented with histories of ovarian surgery, radiotherapy or chemotherapy. Among the other 120 cases, 18 manifested amenorrhea before or at 25 years of age, 102 developed amenorrhea after age 25. In the former group, 16 (88.9%) showed unilateral or bilateral gonadal dysgenesis, and the other 2(11.1%) were defined as resistant ovaries. Abnormalities of sex chromosome karyotype occurred in 44.4% (8/ 18). In the latter group, 68 underwent laparotomy or laparoscopy examination. Morphological and histological examinations of both ovaries showed atrophic ovaries in all cases accompanied by 30.9% (21/ 68) unilateral gonadal dysgenesis; sex chromosomal abnormality was found in only one with no sexual immaturation. The efficacy of estrogen treatment was significantly better among cases with amenorrhea less than 1 year as compared with those longer than 1 year. Clomiphene challenge test given to 8 cases during their irregular menstrual stages produced an elevation of FSH levels to > 20 IU/I. without any response of estradiol secretion. CONCLUSIONS: The earlier estrogen therapy is initiated, the greater possibility of pregnancy will be achieved in cases suffering from hypergonadotropic amenorrhea. The clomiphene challenge test may provide evidence of waning ovarian function for early diagnosis.

Adult↗
PubMed1996

[A clinical study of polytetrafluoroethylene (polytef) as a substitute for conjunctiva].

Burn, tumor or congenital reasons may cause coloboma of conjunctiva. We were seeking for a thin membrane to cover the coloboma that would make the survival peripheral conjunctiva to grow and self-repair so that mucosa transplantation could be avoided. A polytetrafluoroethylene membrane of 0.1 mm thickness, 2-3 mm larger in diameter than the coloboma was sutured in place. After 2-3 weeks the membrane was removed. A total of 16 patients underwent the operation. Of them there were 2 of plasmacytoma, 5 of symblepharon, 6 of contracture of socket of eyeball and 3 of complex pterygium. In two to three weeks, the region of coloboma of conjunctiva was found being repaired. On an average 12 months' follow-up study, the eyeball movements in all cases were normal and the eyes looked symmetric. No symblepharon was found. We conclude that the polytetrafluoroethylene is a non-toxic, smooth, non-adhesive and non-distort substance resistant to high and low temperatures. When used as a substitute for conjunctiva at the region of coloboma of conjunctiva, it makes the peripheral normal conjunctiva tissues to grow and repair the coloboma.

Adolescent↗