Biomedical subjects

H Ling

Publications and source records attributed to H Ling.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Purification and identification of siderophore from Aeromonas hydrophila].

Siderophore of Aeromonas hydrophila(Ah) J-1 was purified from culture supernatant by polyamide column chromatography, eluted by double-distilled water, ethyl acetate precipitated, lyophilized, then the white powder was collected, and demonstrated by CAS and Arnow assay. The siderophore was phenolate, composed of 2,3-dihydroxybenzoic acid (2,3-DHB), lysine, glycine and tryptophan by HPLC. Being cultured iniron-deficient medium, the purified siderophore could stimulated the growth of Ah N9a which siderophore production is poorly positive and reverse the inhibition growth of EDDA. It suggested that siderophore could promote growth of bacteria and might play an important role in bacteria infection.

Aeromonas hydrophila↗

PubMed1999

Inhibition of infection of incoming HIV-1 virus by RNA-cleaving DNA enzyme.

Nine different DNA enzymes (DzV3-n, n=1-9) targeting the V3 loop region of HIV-1 HXB2 were synthesized. One of those, DzV3-9, efficiently cleaved the target in the conserved sequence in the RNA transcript in vitro. DzV3-9 was stable in the cells and inhibited replication of both NL432 and SF162 strains in U87 cells expressing CD4 and co-receptors. The inhibitory effect of DNAzyme on incoming HIV-1 was also demonstrated with pseudotype virions generated by NL432-based luciferase reporter genes. Thus, an efficient, stable DNAzyme against a functionally important region of HIV-1 was identified, and it may be useful for prevention of HIV-1 infection.

Antiviral Agents↗

PubMed1999

Carpentier-Edwards standard and supraannular porcine bioprostheses: comparison of technology.

BACKGROUND: Performance with regard to structural valve deterioration (SVD) with the Carpentier-Edwards standard (CE-S) and supraannular (CE-SAV) (Baxter Healthcare Corp, Irvine, CA) porcine bioprostheses was evaluated to determine whether progress in reduction of structural failure has been achieved with technological changes. METHODS: The CE-S was implanted during 567 aortic valve replacement (AVR) and 486 mitral valve replacement (MVR) procedures, and the CE-SAV was implanted during 1,670 AVR and 1,096 MVR procedures. The failure mode of early stent dehiscence with the CE-SAV prosthesis, thought to be controlled by manufacturing changes in 1986 and 1987, supported comparison of the CE-SAV with censored cases of stent dehiscence. Stent dehiscence accounted for only 1.2% (1 of 81) and 14.1% (29 of 205) of AVR and MVR CE-SAV failures, respectively. RESULTS: The only difference for AVR for freedom from SVD occurred in the 21- to 40-year age group at 15 years and was 68% for the CE-SAV and 31% for the CE-S (p<0.05). In the 61- to 70-year age group, freedom from SVD at 15 years was 76% for the CE-S and 84% for the CE-SAV; for the 71-year or higher age group, freedom from SVD was 89% and 95%, respectively (p = NS). For MVR freedom from SVD was different only in the 71-year or higher age group and was 90% for the CE-S and 59% for the CE-SAV (p<0.05). Freedom from SVD was reduced but was similar (p = NS) for the other age groups. For AVR the actual freedom from SVD at 15 years for the CE-S and CE-SAV was, respectively, 79% and 72% for the 51- to 60-year age group, 86% and 91% for the 61- to 70-year age group, and 98% and 98% for the 71-year or higher age group. For MVR, these rates were, respectively, 69% and 75% for the 61- to 70-year age group and 96% and 89% for the 71-year and higher age group. CONCLUSIONS: The technologic advancements made in the second-generation CE-SAV bioprosthesis to reduce the incidence of structural failure have not uniformly been successful. The actual freedom from SVD provides evidence for implantation of porcine bioprostheses for AVR in age groups 61 to 70 years and 71 years or higher and for MVR in the age group 71 years or higher.

Adult↗

PubMed1999

Thyroid antibody titer and avidity in patients with recurrent miscarriage.

OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.

Abortion, Habitual↗

PubMed1999

The pulmonary venous systolic flow pulse--its origin and relationship to left atrial pressure.

OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.

Aged↗

PubMed1999

Effect of nitric oxide donors on renal tubular epithelial cell-matrix adhesion.

BACKGROUND: Nitric oxide (NO) and its metabolite, peroxynitrite (ONOO-), are involved in renal tubular cell injury. We postulated that if NO/ONOO- has an effect to reduce cell adhesion to the basement membrane, this may contribute to tubular obstruction and may be partially responsible for the harmful effect of NO on the tubular epithelium during acute renal failure (ARF). METHODS: We examined the effect of the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate (DETA/NO), spermine NONOate (SpNO), and the ONOO- donor 3-morpholinosydnonimine (SIN-1) on cell-matrix adhesion to collagen types I and IV and fibronectin using three renal tubular epithelial cell lines: LLC-PK1, BSC-1, and OK. RESULTS: In LLC-PK1 cells, DETA/NO (500 microM) had no effect, and SpNO (500 microM) had a modest effect on cell adhesion compared with controls. Exposure to SIN-1 caused a dose-dependent impairment in cell-matrix adhesion. Similar results were obtained in the different cell types and matrix proteins. The effect of SIN-1 (500 microM) on LLC-PK1 cell adhesion was not associated with either cell death or alteration of matrix protein and was attenuated by either the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, the superoxide scavenger superoxide dismutase, or the ONOO- scavenger uric acid in a dose-dependent manner. CONCLUSIONS: These results therefore support the possibility that ONOO- generated in the tubular epithelium during ischemia/reperfusion has the potential to impair the adhesion properties of tubular cells, which then may contribute to the tubular obstruction in ARF.

Animals↗

PubMed1999

Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice.

Renal ischemia-reperfusion (I/R) injury was investigated in inducible nitric oxide synthase (iNOS) knockout mice. After a 26-min bilateral renal pedicle clamp, serum creatinine concentrations (in mg/dl) in wild-type mice after a 24-h reperfusion were 0.25 +/- 0.03 in sham-operated controls and 2.3 +/- 0.38 in ischemic mice (P < 0. 01); after 48 h, concentrations (in mg/dl) were 0.25 +/- 0.03 in controls and 2.0 +/- 0.18 in ischemic mice (P < 0.01). iNOS knockout mice demonstrated an attenuation of serum creatinine concentration after renal I/R injury. Serum creatinine concentrations (mg/dl) after a 24-h reperfusion were 2.3 +/- 0.22 in wild-type ischemic and 1.21 +/- 0.25 in iNOS knockout ischemic mice (P < 0.05); after 48 h, concentrations were 2.0 +/- 0.18 in wild-type ischemic and 0.96 +/- 0.25 in iNOS knockout ischemic mice (P < 0.01). Histological scoring of acute tubular necrosis in iNOS knockout mice was decreased compared with that in wild-type controls (0.88 +/- 0.2 vs. 3.3 +/- 0. 3, P < 0.05). iNOS protein in the renal cortex of wild-type mice subjected to renal I/R injury was undetectable up to 48 h. However, a strong upregulation of heat shock protein 72 expression was observed in renal cortex of iNOS knockout mice under basal conditions. In conclusion, kidneys of iNOS knockout mice were protected against ischemic acute renal failure. This protective effect may be related to a compensatory upregulation of heat shock protein 72.

Animals↗

PubMed1999

Bileaflet mechanical prostheses for aortic valve replacement in patients younger than 65 years and 65 years of age or older: major thromboembolic and hemorrhagic complications.

OBJECTIVE: To determine major thromboembolic and hemorrhagic complications and predictive risk factors associated with aortic valve replacement (AVR), using bileaflet mechanical prostheses (CarboMedics and St. Jude Medical). DESIGN: A case series. SETTING: Cardiac surgical services at the teaching institutions of the University of British Columbia. PATIENTS AND METHODS: Patients 2 age groups who had undergone AVR between 1989 and 1994 were studied. Group 1 comprised 384 patients younger than 65 years. Group 2 comprised 215 patients 65 years of age and older. RESULTS: The linearized rates of major thromboembolism (TE) occurring after AVR were 1.54%/patient-year for group 1 and 3.32%/patient-year for group 2; the rates for major TE occurring more than 30 days after AVR were 1.13%/patient-year for group 1 and 1.55%/patient-year for group 2. The crude rates for major TE occurring within 30 days of AVR were 1.04% for group 1 and 3.72% for group 2. The death rate from major TE in group 1 was 0.31%/patient-year and in group 2 was 0.88%/patient-year. Of the major TE events occurring within 30 days, 100% of patients in both age groups were inadequately anticoagulated at the time of the event, and for events occurring more than 30 days after AVR, 45% in group 1 and 57% in group 2 were inadequately anticoagulated (INR less than 2.0). The overall linearized rates of major hemorrhage were 1.54%/patient-year for group 1 and 2.21%/patient-year for group 2. There were no cases of prosthesis thrombosis in either group. The mean (and standard error) overall freedom from major TE for group 1 patients at 5 years was 95.6% (1.4%) and with exclusion of early events was 96.7% (1.3%); for group 2 patients the rates were 90.0% (3.2%) and 93.7% (3.0%), respectively. The mean (and SE) overall freedom from major and fatal TE and hemorrhage for group 1 patients was 90.1% (2.3%) and with exclusion of early events was 91.2% (2.3%); for group 2 patients the rates were 87.9% (3.1%) and 92.5% (2.9%), respectively. The 5-year rate for freedom from valve-related death for group 1 patients was 96.3% (2.1%) and for group 2 patients was 97.2% (1.2%). CONCLUSION: The thromboembolic and hemorrhagic complications after AVR with bileaflet mechanical prostheses occur more frequently and result in more deaths in patients 65 years of age and older than in patients years younger than 65 years.

Adult↗

PubMed1999

[Application of power band graph method to the modeling and simulation of cardiovascular system].

This paper presents a computer simulation model of the cardiovascular circulation system, which describes the blood flow dynamic law in the cardiovascular system by the state equation. The model can be used in physiological study and computer-aided medical education. In this paper, the Power Band Graph (PBG) modeling method is used to realize modeling of the human circulation system and conduct a simulation study on a simplified physiological system model. The results demonstrate that the PBG method, as an understandable and unity modeling method, is quite effective and practicable and can be used widely in the field of physiological system simulation.

Computer Simulation↗

PubMed1999

[Cloning and sequencing of human papillomavirus 16 L1 gene from cervical carcinoma tissues of Chinese women].

OBJECTIVE: Human papillomavirus type 16 (HPV16) is highly related with the development of cervical carcinoma. HPV16 late gene L1 encodes its main capsid protein. This study is to analyze the whole sequence of L1 gene of HPV16 of the Chinese isolates. METHODS: Three samples of HPV16 L1 gene were amplified from cervical carcinoma tissues of Chinese patients by PCR and then cloned and sequenced. RESULTS: There were four sites in nucleic acid sequences of all three HPV16 L1 fragments were different from the originally reported sequence of HPV16 and the differed sequences had changed the triplet codes, therefore, subsequently changed the amino acids it coded. CONCLUSION: The results showed that some mutation had taken place in the nucleotide sequence of L1 gene of HPV16 obtained from the cervical carcinoma tissues of Chinese women.

Capsid Proteins↗

PubMed1998

Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3.

Shiga-like toxin I (SLT-I) is a virulence factor of Escherichia coli strains that cause disease in humans. Like other members of the Shiga toxin family, it consists of an enzymatic (A) subunit and five copies of a binding subunit (the B-pentamer). The B-pentamer binds to a specific glycolipid, globotriaosylceramide (Gb3), on the surface of target cells and thereby plays a crucial role in the entry of the toxin. Here we present the crystal structure at 2.8 A resolution of the SLT-I B-pentamer complexed with an analogue of the Gb3 trisaccharide. The structure reveals a surprising density of binding sites, with three trisaccharide molecules bound to each B-subunit monomer of 69 residues. All 15 trisaccharides bind to one side of the B-pentamer, providing further evidence that this side faces the cell membrane. The structural model is consistent with data from site-directed mutagenesis and binding of carbohydrate analogues, and allows the rational design of therapeutic Gb3 analogues that block the attachment of toxin to cells.

Bacterial Toxins↗

PubMed1998

Modeling the carbohydrate-binding specificity of pig edema toxin.

The wild-type binding pentamer of Shiga-like toxin IIe (SLT-IIe) binds both the globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4) cell surface glycolipids, whereas the double mutant GT3 (Q65E/K67Q) exhibits a marked preference for Gb3 [Tyrrell, G. J., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 524-528]. We modeled three unique sites (sites 1-3) for binding of the carbohydrate moiety of Gb3 to GT3 and SLT-IIe, on the basis of the three sites observed for the SLT-I pentamer [Ling, H., et al. (1998) Biochemistry 37, 1777-1788]. Examination of the three sites in light of various mutation and binding data strongly suggested that one of the binding sites plays a role in the change of specificity observed for the GT3 mutant. We applied several modeling techniques, and developed a model for binding of the carbohydrate moiety of Gb4 to this site of the SLT-IIe binding pentamer. This model is consistent with a wide variety of mutation and binding data and clearly shows the importance of the terminal GalNAc residue of Gb4, as well as that of the two mutated residues of GT3, to the intermolecular interaction.

Amino Acid Sequence↗

PubMed1998

Carpentier-Edwards supraannular porcine bioprosthesis evaluation over 15 years.

BACKGROUND: The Carpentier-Edwards supraannular porcine bioprosthesis experience during 15 years has been evaluated to determine the incidence of structural valve deterioration by valve position in various age groupings. METHODS: From 1981 to 1995, 2,943 patients older than 20 years had the prosthesis implanted in 3,024 procedures. The mean age of the population was 65.5+/-11.9 years (range, 21 to 89 years). Aortic valve replacement was performed in 1,657 patients (54.8%); mitral valve replacement, 1,092 (36.1%); multiple valve replacement, 253 (8.3%); pulmonary valve replacement, 2 (0.1%); and tricuspid valve replacement, 20 (0.7%). Concomitant procedures were performed in 1,332 patients (45.3%), and 352 (12.0%) had previous procedures. RESULTS: The early mortality was 8.9% (270), only 0.4% (11) valve-related. The total follow-up was 17,471 years (mean, 5.9+/-4.1 years). The late mortality was 5.2%/ patient-year (901) with the valve-related component 1.0%/patient-year (171). The reoperation rate was 2.1%/ patient-year (369) with 4.3% mortality (16). The linearized rate of structural valve deterioration was 2.0%/patient-year (341), and overall complications, 5.9%/patient-year (1,019). The overall survival, at 15 years, was 31.1%+/2.8% (p < 0.05; aortic valve replacement greater than mitral valve replacement or multiple valve replacement). The freedom from structural valve deterioration for aortic valve replacement was, at 12 years, for patients older than 70 years, 95.3%+/-2.7%; 61 to 70 years, 92.9%+/-2.1%; 51 to 60 years, 70.1%+/-5.3%; 41 to 50 years, 60.0%+/-8.8%; and 21 to 40 years, 75.7%+/-7.3%. The freedom from structural valve deterioration for mitral valve replacement was, at 12 years, for patients older than 70 years, 66.1%+/-9.7%; 61 to 70 years, 53.1%+/-4.7%; 51 to 60 years, 52.6%+/-5.5%; 41 to 50 years, 39.3%+/-6.9%; and 21 to 40 years, 42.1%+/-9.4%. CONCLUSIONS: The prosthesis is recommended for aortic valve replacement for patients older than 70 years and for patients 61 to 70 years (when extended longevity is not anticipated) and for mitral valve replacement for patients older than 70 years (when extended longevity is not anticipated).

Adult↗

PubMed1998

Effect of hypoxia on proximal tubules isolated from nitric oxide synthase knockout mice.

Nitric oxide (NO) has been shown to be a mediator of hypoxic injury in rat renal proximal tubules (PT). However, the role of NO in hypoxic injury to mouse. PT has not been examined. The aim of the present study was to determine the effect of knockout of nitric oxide synthase (NOS) isoforms on hypoxic injury in mouse PT. Mouse PTs were isolated by collagenase digestion and Percoll centrifugation. The nonselective NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 10 mM), but not its inactive stereoisomer D-NAME, protected against hypoxic injury as assessed by LDH release. Carboxy-imidazolineoxyl N-oxide (carboxy-PTIO, 100 microM), a stable NO scavenger, also afforded cytoprotection against hypoxic injury. To determine the role of the different NOS isoforms in the hypoxic injury, we examined the effect of hypoxia on PT isolated from knockout mice in which either the inducible NOS (iNOS) endothelial NOS (eNOS) or neuronal NOS (nNOS) gene was lacking. PT isolated from iNOS knockout mice were resistant to hypoxic injury compared to wild-type controls. In contrast, PT isolated from both nNOS and eNOS knockout mice were not protected against hypoxic injury. In conclusion, the present study demonstrates that NO is a mediator of hypoxic PT injury in the mouse and that knockout of the iNOS gene is cytoprotective against this hypoxic PT injury.

Animals↗

PubMed1998

Mesangial cell hypertrophy induced by NH4Cl: role of depressed activities of cathepsins due to elevated lysosomal pH.

Enhanced ammoniagenesis is currently thought to play an important role in renal hypertrophy and subsequent tubulointerstitial fibrosis. Under certain conditions glomeruli also may be affected by ammonia toxicity. Exposure of glomeruli to augmented ammonia levels may occur: (i) in advanced liver diseases due to elevated blood ammonia concentrations; (ii) in conditions of enhanced tubular ammoniagenesis following cortical "trapping;" and (iii) due to increased ammonia formation in the glomeruli in the presence of impaired renal function. To elucidate the potential role of ammonia in glomerular injury, we investigated the effect of NH4Cl on protein turnover as well as on activities of various cathepsins in cultured rat mesangial cells. The results show that NH4Cl (20 mM) induced cell hypertrophy as defined by an increase in both cell protein content and cell volume (+38% and +10.1%, respectively, after 48 hr). This hypertrophy was associated with suppression of the activities of cathepsins B and L + B (-56.8% and -51.3% after 48 hr) and reduction of protein degradation rate (-61% after 48 hr), but without enhanced protein synthesis. Inhibition of Na+/H+ antiport by amiloride (1 mM) neither prevented the reduction of cathepsin activities nor the hypertrophy of the mesangial cells. Upon NH4Cl application lysosomal pH was elevated. This alkalinization may be causatively involved in the impairment of cathepsin B and L + B due to shifting the lysosomal pH above the optimum of their activities. In conclusion, NH4Cl induces hypertrophy but not hyperplasia in mesangial cells. This hypertrophy is caused by the reduction of protein degradation, mainly due to depressed activities of cathepsin B and L + B in the absence of enhanced protein synthesis. A shift of lysosomal pH above the optimum of the acidic cathepsins seems to be a key factor in their impaired activities in mesangial cells.

Ammonium Chloride↗

PubMed1998

High-glucose media enhance the responsiveness of tubular cells to growth promoters: effect on lysosomal cathepsins and protein degradation.

Nephromegaly is a prominent feature of diabetic nephropathy and predominantly reflects increased renal tubule mass, mostly due to hypertrophy. To elucidate pathogenetic factors involved, we studied the effects of high glucose (HG) alone, and in combination with hormones/growth promoters: angiotensin II (10(-7) M); parathyroid hormone (10(-7) M); insulin-like growth factor-1 (10(-7) M), or transforming growth factor-beta1 (TGF-beta1, 10 ng/ml) in a renal cell line (LLC-PK1) with many characteristics of the proximal tubule. Activities of lysosomal cathepsins (B, L+B and H) and the protein turnover were investigated. Exposure to HG (25 mM) for up to 48 h increased cellular protein content, due to enhanced protein synthesis, while protein degradation rate and cathepsin activities tended to lower values. Hyperosmotic mechanisms of glucose action were excluded, since these effects were not induced by mannitol. In normoglycemic conditions only TGF-beta1 decreased cathepsin activities and protein degradation rate significantly. However, in HG media all applied hormones/growth factors significantly lowered the protein degradation rate, as well as lysosomal cathepsin activities. The enhanced responsiveness could contribute to the impaired protein turnover, with consequent hypertrophy of the tubulointerstitium in diabetic nephropathy.

Angiotensin II↗

PubMed1998

Advanced glycated albumin impairs protein degradation in the kidney proximal tubules cell line LLC-PK1.

Advanced glycation end-products (AGEs) are assumed to play a major role in the genesis of diabetic nephropathy and other diabetic complications. We studied the potential effect of AGEs on protein turnover and lysosomal proteinase activities in LLC-PK1 cells, a pig kidney proximal tubules cell line. Advanced glycated bovine serum albumin (AGE-BSA) was used as a model of AGEs and its action was compared to that of nonglycated BSA. AGE-BSA but not BSA (50 micromol/l) induced a significant increase in cell volume (BSA: 4870.6 +/- 74.8 fl, AGE-BSA: 5718.0 +/- 20.7 fl, p<0.01). Protein degradation rate was decreased by 13.8% after 48 hrs. incubation with AGE-BSA (p<0.01) while protein synthesis increased by 19,1%, (p<0.01). After incubation with AGE-BSA but not BSA activities of lysosomal cathepsins (B, L+B and H) decreased in a time- and dose-dependent fashion. This decline was neither caused by a shift in lysosomal pH outside the optimal range for cathepsins, nor by a direct inhibitory effect of AGEs modified proteins or peptides but most probably by inhibition of cathepsin B expression as measured by RT-PCR. It is supposed that impaired protease activities participated in decreased protein breakdown and cell enlargement. For the first time our data provide the evidence that AGEs induce hypertrophy of LLC-PK1 cells due to decreased protein breakdown resulting from reduced lysosomal proteinase activities with a concomitant stimulation of protein synthesis.

Animals↗

PubMed1997

A high-resolution genetic map around waltzer on mouse chromosome 10 and identification of a new allele of waltzer.

A new autosomal recessive mouse mutation characterized by deafness and circling behavior was recovered during mutagenesis experiments with chlorambucil (CHL). On the basis of allelism tests and linkage analyses, this mutation appears to represent a new allele of waltzer (v) that maps to mouse Chromosome (Chr) 10. We have designated this new allele, Albany waltzer (vAlb). A high-resolution map of the region around v was constructed from data from two intersubspecific backcrosses involving Mus musculus castaneus. The analysis of 648 backcross mice has allowed vAlb to be localized 1.1 +/- 0.4 cM distal to D10Mit60 and 0.2 +/- 0.2 cM proximal to a cluster of four markers, D10Mit172, D10Mit112, D10Mit48, and D10Mit196. An independent backcross was used to confirm the map order and distances in the vAlb backcross. The two linkage maps were consistent, indicating that the lesion in vAlb, which is presumed to be a deletion based on the known action of CHL, is small and has not significantly altered the map at this level of detection. Additionally, three genes (Ros1, Grik2, and Zfa) were eliminated as possible candidates for vAlb, and several SSLP markers were separated genetically.

Alleles↗