Search PubMed⌕ Search

Biomedical subjects

R Chun

Publications and source records attributed to R Chun.

At least 19 recordsLinked to original sources
PubMed2005

Lineage differentiation of canine lymphoma/leukemias and aberrant expression of CD molecules.

Multiparameter flow cytometry analysis and specific cluster differentiation (CD) molecules were used to determine the expression profiles of B- and T-cell antigens on lymph node preparations from 59 dogs with generalized or multisystemic lymphoma. Lymph node samples from 11 healthy dogs were labeled to validate the specificity of antibodies and to formulate guidelines for interpretation of the results obtained from lymphoma samples. In normal lymph nodes, T-lymphocytes expressing CD3, CD4, or CD8 beta represented 59+/-11%, 43+/-8%, or 16+/-5% of the total cells, whereas B-lymphocytes expressing either CD21 or surface IgM (IgM) represented 37+/-9% or 14+/-5%, respectively. Small lymphocytes could be distinguished from large lymphocytes by forward light scatter. Of the patient samples 29 different breeds were represented with Golden and Labrador retriever being the most common. The lymphoma samples segregated into three groups based on CD antigen expression. Thirty cases predominantly expressed one or more combinations of CD79a, IgM, and CD21 representing a B-cell lineage. Three B-cell cases also expressed the stem cell antigen, CD34. Sixteen cases expressed one or more combinations of CD3, CD4, and CD8 consistent with a T-cell lineage and CD3+CD4+CD8--phenotype was the most common. Thirteen cases showed a mixed expression profile for T- and B-cell antigens and in three cases CD14 was highly expressed. Clinical response was poorest for T-cell lymphomas. Leukemic states occurred in all three phenotypes; but mixed cell cases had the greatest proportion. Dual immunofluorescence staining confirmed co-expression of T-cell (CD3) and B-cell antigens (CD79a or CD21) on neoplastic lymphocytes of six mixed cell cases. In one mixed cell case, dual immunostaining identified lymphocyte populations that stained mutually exclusive for CD79a and CD3. Six mixed cell lymphomas tested by PCR showed clonality for rearranged antigen receptor. Four cases that were CD79a+CD3+ had TCRgamma chain gene rearrangements, whereas two cases that were CD3+CD8+CD21+ had Ig heavy chain rearrangement. One case expressing multiple CD molecules (CD3+CD8+CD21+CD14+) was PCR negative for both Ig and TCRgamma gene rearrangement and could not be classified into a B- or T-cell lineage. We show for the first time co-expression of B- and T-cell markers on lymphoma cells that had specific T- or B-cell gene rearrangements. These findings suggest that aberrant CD molecule expression is not an uncommon finding in canine lymphomas and is a useful diagnostic marker for malignancy.

Animals↗
PubMed2005

Multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine in the cat.

The purpose of this study was to evaluate the multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine alone and in combination in cats. Seven healthy cats were included in this randomized-crossover study. The cats were assigned to groups designated to receive cimetidine alone (15 mg/kg, p.o., q12 h), piroxicam alone (0.3 mg/kg, p.o., q24 h), and piroxicam combined with cimetidine (both at aforementioned doses). The cats were dosed for 10 days followed by at least a 2-week washout period between trials. Serial blood samples were collected following the first and last doses and analyzed utilizing a high-performance liquid chromatography with mass spectrometry detection (LC/MS) assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Endoscopic evaluation of the gastric mucosa was performed and serum urea nitrogen (SUN), creatinine, alkaline phosphatase (ALP), and alanine transaminase (ALT) activities were evaluated. There were not a clinically relevant difference between the pharmacokinetic parameters of piroxicam administered alone or in combination with cimetidine after either the first or last dose. Gastric ulcers were not observed in any cats although gastric erosions were. The SUN, creatinine, ALP, and ALT activities remained within reference ranges for all cats. It appears that once daily, short-term use of piroxicam alone and in combination with cimetidine in cats is relatively safe based on the parameters evaluated in this study. However, further studies are necessary to determine the long-term gastrointestinal safety of piroxicam.

Administration, Oral↗
PubMed2003

Single dose pharmacokinetics of piroxicam in cats.

Piroxicam (PIRO) is a nonsteroidal anti-inflammatory drug (NSAID) recognized for its value as a chemopreventative and anti-tumor agent. Eight cats were included in this study. PIRO was administered in a single oral (p.o.) and intravenous (i.v.) dose of 0.3 mg/kg. The study was designed as a randomized complete crossover with a 2-week washout period. Serial blood samples were collected after each dose and plasma was analyzed for PIRO. Pharmacokinetic parameters of PIRO were determined using noncompartmental analysis. PIRO is well absorbed in the cat with a median bioavailability (F) of 80% (range 64-124%). The median i.v. t1/2 was 12 h (range 8.6-14 h). The median Cmax was 519 ng/mL with a corresponding Tmax of 3 h. PIRO appears to be rapidly absorbed following p.o. administration in cats with a higher Cmax and AUC than in dogs.

Administration, Oral↗
PubMed2001

Differential expression of various cytokine and chemokine genes between proliferative and non-proliferative glomerulonephritides.

BACKGROUND: Intraglomerular cellular proliferation is one of the major determinants for dividing various glomerulonephritis (GN) into two groups, such as proliferative versus non-proliferative. Cytokines and chemokines are involved in the pathogenetic pathways and would affect the functional and histologic sequelae. We hypothesized that the morphological difference might be based on the differential intrarenal expression of various cytokines and chemokines. We quantified the intrarenal gene expression of various cytokines and chemokines, and correlated it with clinical parameters. METHODS: Total RNA was extracted from 54 proliferative GN (PGN) core biopsy specimens and 42 non-proliferative GN (NPGN) specimens. Using the internal competitors, RT-PCR was instituted to quantify mRNAs. RESULTS: The magnitude of the gene expressions of IL-2, IFN-gamma, and IFN-gamma/IL-10 ratio were significantly higher in PGN than in NPGN. RANTES and IL-8 had more abundant gene messages in PGN. It was shown that Th1 cytokine was upregulated if GN was mediated by immune complexes regardless of cellular proliferation. But chemokines had the elevated levels of expression in PGN among immune complex-mediated GN. Up-regulation of the IFN-gamma/IL-10 ratio and TNF-alpha was associated with poor renal function at the time of biopsy. Renal tissues from the patients with a non-nephrotic range of proteinuria showed abundant messages for proinflammatory cytokines and chemokines. CONCLUSION: Th1, proinflammatory cytokines, and chemokines were more abundant in proliferative GN, and correlated with unfavorable clinical parameters. We propose that the clinical manifestations and diverse histologic features of human GN are associated with differential expressions of specific cytokines and chemokines.

Adolescent↗
PubMed1999

A line in the sand.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1999

Results of renal ultrasonography performed before and during administration of saline (0.9% NaCl) solution to induce diuresis in dogs without evidence of renal disease.

OBJECTIVE: To evaluate the effect of saline (0.9% NaCl) solution administered IV to induce diuresis on 15 dimensional variables of the kidneys, size of renal pelvis, and diameter of the cranial part of the ureters. ANIMALS: 25 dogs without evidence of renal disease that were undergoing chemotherapy for various neoplasms. PROCEDURE: The kidneys, cranial aspect of the ureters, and trigone area of the urinary bladder of each dog were examined ultrasonographically before and during IV administration of saline solution (2.7 to 18.8 ml/kg of body weight/h). RESULTS: Ultrasonography revealed unilateral and bilateral pyelectasis during diuresis in 16 of 23 (70%) dogs but unilateral pyelectasis in only 1 dog before diuresis. Unilateral pyelectasis during diuresis was observed in 11 of 16 (69%) dogs. Pyelectasis during diuresis was categorized as slight in 15 of 21 (71%) kidneys. Degree of pyelectasis during diuresis was not identical in both kidneys of 13 of 16 (81 %) dogs. Diuresis did not induce ureterectasis, and it did not cause changes in 15 dimensional variables of the kidneys. CONCLUSIONS: In nonsedated, nonazotemic dogs, IV administration of saline solution to induce diuresis may cause slight pyelectasis without evidence of ureterectasis. CLINICAL RELEVANCE: When dilatation of the cranial part of the ureter is > 2 mm at the same time that ipsilateral pyelectasis is detected during ultrasonographic examination of the urinary tract system of a nonsedated, nonazotemic dog receiving IV administration of saline solution to induce diuresis, additional examinations are recommended to determine the possibility of early obstructive nephropathy or pyelonephritis.

Animals↗
PubMed1999

Hypothermia and the trauma patient.

Hypothermia has profound effects on every system in the body, causing an overall slowing of enzymatic reactions and reduced metabolic requirements. Hypothermic, acutely injured patients with multisystem trauma have adverse outcomes when compared with normothermic control patients. Trauma patients are inherently predisposed to hypothermia from a variety of intrinsic and iatrogenic causes. Coagulation and cardiac sequelae are the most pertinent physiological concerns. Hypothermia and coagulopathy often mandate a simplified approach to complex surgical problems. A modification of traditional classification systems of hypothermia, applicable to trauma patients is suggested. There are few controlled investigations, but clinical opinion strongly supports the active prevention of hypothermia in the acutely traumatized patient. Preventive measures are simple and inexpensive, but the active reversal of hypothermia in much more complicated, often invasive and controversial. The ideal method of rewarming is unclear but must be individualized to the patient and institution specific. An algorithm reflecting newer approaches to traumatic injury and technical advances in equipment and techniques is suggested. Conversely, hypothermia has selected clinical benefits when appropriately used in cases of trauma. Severe hypothermia has allowed remarkable survivals in the course of accidental circulatory arrest. The selective application of mild hypothermia in severe traumatic brain injury is an area with promise. Deliberate circulatory arrest with hypothermic cerebral protection has also been used for seemingly unrepairable injuries and is the focus of ongoing research.

Algorithms↗
PubMed1998

Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.

A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated (Stealth) liposome. The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double-blind fashion to receive either oral pyridoxine or placebo daily during Doxil chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutaneous toxicity was determined by clinical and histological scoring. No difference was observed in remission rates (71.4 versus 75%) achieved between groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely abrogate PPES; however, it occurred later and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dose of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received a median of 2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028). A trend (P = 0.084) toward prolongation of remission length was observed in dogs receiving pyridoxine, which was likely attributable to their ability to receive more Doxil without delay or discontinuation. We conclude that pyridoxine is effective in delaying the onset and severity of PPES in this canine model.

Animals↗
PubMed1997

Preclinical trial of doxorubicin entrapped in sterically stabilized liposomes in dogs with spontaneously arising malignant tumors.

PURPOSE: To prospectively evaluate the short-term toxicoses associated with pegylated-liposomal doxorubicin (Doxil) administered to dogs with measurable tumors of various histologic types and sites. Preliminary information regarding efficacy was also generated. METHODS: A group of 51 dogs with histologically confirmed malignancies received a total of 103 Doxil treatments given i.v. every 3 weeks at dosages ranging from 0.75 to 1.1 mg/kg in the context of a phase I dose-escalation trial. Acute and short-term toxicities as well as tumor response and duration of response were characterized. RESULTS: The maximally tolerated dose in tumor-bearing dogs was established as 1.0 mg/kg i.v. every 3 weeks. The dose-limiting toxicity was a cutaneous toxicity clinically resembling palmar-plantar erythrodysesthesia (PPES). An overall response rate of 25.5% was observed with five complete responders and eight partial responders. CONCLUSIONS: Doxil appeared to be well tolerated at dosages similar to those tolerated for free doxorubicin in tumor-bearing dogs. PPES was the dose-limiting toxicity encountered, rather than myelosuppresion as is the case with free doxorubicin in dogs. Doxil as a single agent may have a broad spectrum of activity and deserves further evaluation.

Animals↗
PubMed1996

Cisplatin treatment of transitional cell carcinoma of the urinary bladder in dogs: 18 cases (1983-1993).

OBJECTIVE: To determine whether cisplatin administered at a dosage of 60 mg/m2 of body surface area, IV, every 21 days, would induce remission of transitional cell carcinoma of the urinary bladder in dogs. DESIGN: Retrospective analysis of medical records. ANIMALS: 18 dogs with histologically confirmed transitional cell carcinoma of the urinary bladder. PROCEDURE: Clinical staging was performed by means of physical examination, contrast cystography or ultrasonography, and thoracic radiography prior to and 42 days after the initiation of cisplatin treatment. Dogs with clinical signs of tumor progression were reevaluated earlier than 42 days in some instances. Complete remission (CR) was defined as complete resolution of measurable tumor. Partial remission (PR) was defined as a > or = 50% reduction in tumor volume without development of new tumors. Stable disease was defined as < 50% change in tumor volume at 42 days without development of new lesions. Progressive disease (PD) was defined as > or = 50% increase in tumor volume or development of new tumors at any time. Dogs were reevaluated at 42-day intervals until they had a CR, developed PD, or developed unacceptable adverse effects. RESULTS: Three dogs had a PR, 4 had stable disease, and 9 had PD. Tumor response could not be assessed in 2 dogs: 1 dog developed grand mal seizures 3 hours after the first dose of cisplatin was given and was euthanatized; the other dog continued to have clinical signs of urinary tract obstruction and was euthanatized 8 days after the first dose of cisplatin. Four dogs developed renal azotemia that was suspected to be secondary to cisplatin nephrotoxicity. CLINICAL IMPLICATIONS: The cisplatin dosage was higher than that reported in studies of dogs with transitional cell carcinoma of the bladder. Even with this higher dosage, none of the dogs had a CR, and only 3 of 18 had a PR. A more effective, less toxic treatment for transitional cell carcinoma in dogs is needed.

Animals↗
PubMed1996

Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978-1992).

OBJECTIVE: To characterize the frequency, clinical signs, biologic behavior, and response to treatment of tumors of the ear canal in dogs and cats. DESIGN: Retrospective analysis of medical records. ANIMALS: Medical records of 81 dogs (48 malignant tumors, 33 benign tumors) and 64 cats (56 malignant tumors, 8 benign tumors). PROCEDURE: Data were analyzed for cats and dogs with malignant tumors, and risk factors were analyzed for their potential impact on survival time. RESULTS: Malignant tumor types most commonly reported included ceruminous gland adenocarcinoma, squamous cell carcinoma, and carcinoma of undetermined origin. Median survival time of dogs with malignant aural tumors was > 58 months, whereas that of cats was 11.7 months. A poor prognosis was indicated by extensive tumor involvement (dogs) and by neurologic signs at time of diagnosis, diagnosis of squamous cell carcinoma or carcinoma of undetermined origin, and invasion into lymphatics or blood vessels (cats). CLINICAL IMPLICATIONS: Malignant tumors of the ear canal in dogs and cats have a propensity for local invasion, but tend not to metastasize. Squamous cell carcinoma and carcinoma of undetermined origin were the most locally aggressive tumors. Malignant tumors of the ear canal are best managed by aggressive surgical excision. Radiotherapy may be useful when tumors cannot be completely removed.

Adenocarcinoma↗
PubMed1996

DNA repair deficiencies associated with mutations in genes encoding subunits of transcription initiation factor TFIIH in yeast.

Several proteins, including Rad3 and Rad25(Ssl2), are essential for nucleotide excision repair (NER) and function in the RNA polymerase II transcription initiation complex TFIIH. Mutations in genes encoding two other subunits of TFIIH, TFB1 and SSL1, result in UV sensitivity and have been shown to take part in NER in an in vitro system. However, a deficiency in global NER does not exclude the possibility that such repair-deficient mutants can perform transcription-coupled repair (TCR), as shown for xeroderma pigmentosum group C. To date, temperature-sensitive C-terminal truncations of Tfbl are the only TFIIH mutations that result in intermediate UV sensitivity, which might indicate a deficiency in either the global NER or TCR pathways. We have directly analyzed both TCR and global NER in these mutants. We found that ssl1, rad3 and tfb1 mutants, like rad25(ssl2-xp) mutants, are deficient in both the global NER and TCR pathways. Our results support the view that the mutations in any one of the genes encoding subunits of TFIIH result in deficiencies in both global and TCR pathways of NER. We suggest that when subunits of TFIIH are in limiting amounts, TCR may preclude global NER.

Adenosine Triphosphatases↗
PubMed1993

In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor.

Recent genetic experiments have suggested that tat transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat requires functional upstream enhancer sequences--Sp1 sites, in particular. In these experiments, HeLa cell nuclear extracts were passed over affinity matrices containing chemically synthesized or bacterially expressed HIV-1 Tat. Assay of material that bound to and eluted from the Tat matrices revealed the presence of the Sp1 transcription factor. Other transcription factors (Oct and NF-kappa B) also bound to Tat matrices but with less efficiency--in parallel with the lower capacities of these binding motifs to confer Tat responsiveness on a basal HIV-1 promoter compared with Sp1 sites. Passage of nuclear extracts over matrices containing other neutral proteins, including bovine serum albumin, ovalbumin, and lysozyme, revealed no or reduced binding. Cross-linking experiments indicated that the purified Sp1 and Tat proteins can form multimeric complexes in the absence of other proteins. The region of Tat responsible for Sp1 binding was localized to a region encompassing residues 30 to 62. Immunoprecipitation experiments with HIV-1-infected T lymphocytes indicated coimmunoprecipitation of Tat and Sp1. These experiments extend previous genetic experiments and suggest a direct interaction between Tat and Sp1 during transactivation.

Base Sequence↗
PubMed1991

Intermittent intravalvar regurgitation of a mechanical aortic valve prosthesis--diagnosis and clinical implications. A case report.

Mechanical prosthetic valve regurgitation may be either periprosthetic or intraprosthetic. The latter is usually mild, occurring in the majority of normally functioning valves and is due to the 'regurgitant flow' closing the valve. An unusual case is reported of intermittent intraprosthetic regurgitation through a normally functioning aortic Medtronic-Hall prosthesis caused by tissue ingrowth below the valve 4 years after implantation.

Adult↗