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Biomedical subjects

K C Lee

Publications and source records attributed to K C Lee.

At least 127 records · Page 7Linked to original sources
PubMed1999

Spontaneous renal allograft rupture attributed to acute tubular necrosis.

A renal allograft recipient receiving triple immunosuppressive therapy developed spontaneous allograft rupture 5 days after her second cadaveric renal transplantation. Renal biopsy showed interstitial edema with severe acute tubular necrosis (ATN). There was no evidence of acute rejection or renal vein thrombosis. The ruptured renal graft was salvaged by an aggressive fluid resuscitation therapy and surgical hemostasis. The renal function was satisfactory on discharge. We conclude that renal allograft rupture can be the result of interstitial edema solely attributed to ATN in the absence of graft rejection. The ruptured graft kidney is potentially salvageable for those patients whose hemodynamic status can be stabilized by appropriate supportive therapy.

Adult↗
PubMed1999

Comparison of incidence of gastroesophageal reflux and regurgitation associated with timing of removal of the laryngeal mask airway: on appearance of signs of rejection versus after recovery of consciousness.

STUDY OBJECTIVES: To compare the incidence of gastroesophageal reflux and regurgitation associated with laryngeal mask airway (LMA) removal when signs of rejecting the LMA, such as swallowing, struggling, and restlessness, were observed and when the patient could open his or her mouth on command. DESIGN: Randomized clinical trial. SETTING: Operating room and recovery room of a tertiary care referral hospital. PATIENTS: 63 ASA physical status I and II adult patients scheduled for elective orthopedic surgery. INTERVENTIONS: Using a standardized general anesthetic technique, patients were allocated randomly to Group A (n = 34; LMA removed when signs of rejection, such as swallowing, struggling, and restlessness, were observed) or Group B (n = 29; LMA removed when the patient could open his or her mouth on command). MEASUREMENTS AND MAIN RESULTS: To detect gastroesophageal reflux throughout anesthesia, a pH monitoring probe was positioned in the lower esophagus on the day before surgery. To assess regurgitation during emergence, a gelatin capsule of methylene blue (50 mg) was swallowed prior to induction. At the end of anesthesia, episodes of reflux and regurgitation of gastric contents were analyzed/determined by pH below 4 and bluish staining of the pharynx and/or LMA, respectively. Physical events such as bucking, straining, and coughing during the arousal phase were recorded in both groups by an independent observer. The incidence of reflux (pH < 4) from the time of the appearance of rejection signs to LMA removal and the total incidence of reflux in Group B were significantly higher than in Group A (p < 0.05). Staining of the LMA and the pharynx by methylene blue was not observed in patients from either experimental group. The number of physical events in Group B during the arousal phase was significantly increased compared to Group A (p < 0.05). Considering all patients in Group A and Group B, physical events were associated with the occurrence of reflux (p < 0.05). Desaturation (SpO2 < 95%) and clinical evidence of aspiration of gastric contents did not occur in either group. CONCLUSION: Maintenance of the LMA until the patient can open his or her mouth on command increases the incidence of gastroesophageal reflux.

Adolescent↗
PubMed1999

Increased bioavailability of clomipramine after sublingual administration in rats.

This study examined the absorption and disposition of clomipramine in rats after sublingual (5 and 50 mg/kg), oral (50 mg/kg), and iv (5 mg/kg) administration. The mean oral bioavailability of clomipramine was 24.8% and 29.7%, respectively, in conscious rats and in rats anesthetized with ketamine/xylazine (30/3 mg/kg). When given sublingually in isotonic saline at a dose of 50 mg/kg, clomipramine was rapidly absorbed, and the mean absolute bioavailability (36.2%) was increased over oral dosing. The mean AUC values of clomipramine were 2258 +/- 1762 ng.h/mL and 1891 +/- 867 ng.h/mL after oral administration to conscious and anesthetized rats, respectively, and 3303 +/- 1576 ng.h/mL after sublingual administration to anesthetized rats. Sublingual administration (5 mg/kg doses) of clomipramine formulated with a permeation enhancer, 2-hydroxypropyl beta-cyclodextrin, further increased the sublingual bioavailability to 57.1%. The sublingual route may be an alternative route of administration of clomipramine, providing enhanced bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Isolation, characterization, and stability of positional isomers of mono-PEGylated salmon calcitonins.

PURPOSE: To separate and characterize the different positional isomers of mono-PEGylated salmon calcitonins (mono-PEG-sCTs) and to evaluate the effects of the PEGylation site on the stability of different mono-PEG-sCTs in rat kidney homogenate. METHODS: Mono-PEG-sCTs were prepared using succinimidyl carbonate monomethoxy polyethylene glycol (5,000 Da) and separated by gel-filtration HPLC followed by reversed-phase HPLC. To characterize PEGylated sCTs, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) and reversed-phase HPLC of the trypsin digested samples were performed. Mono-PEG-sCTs and sCT in rat kidney homogenates were measured by column-switching reversed-phase HPLC with on-line detection of the radioiodinated samples using a flow-through radioisotope detector. RESULTS: Three different mono-PEGylated sCTs were separated by reversed-phase gradient HPLC. From the MALDI-TOF MS analysis, the average molecular weight of mono-PEG-sCTs was confirmed as around 8650 Da. The presence of PEG moiety in the mono-PEG-sCTs was also manifested by the fact that the distance between two adjacent mass spectum lines was 44 Da which corresponds to PEG monomer unit. Tryptic digestion analysis demonstrated that these mono-PEG-sCTs are 3 positional isomers of N-terminus, Lys18- and Lys11-residue modified mono-PEGylated sCTs. The degradation half-life of these 3 positional isomers in rat kidney homogenates significantly increased in order of the N-terminus (125.5 min), Lys11- (157.3 min), and Lys18 residue modified mono-PEGylated sCT (281.5 min) over the native sCT (4.8 min). CONCLUSION: Three positional isomers of mono-PEGylated sCTs were purified and characterized. Of these, the resistance to proteolytic degradation was highest for the Lys18-residue modified mono-PEG-sCT. These studies demonstrate that the in vivo stability of PEGylated sCTs is highly dependent on the site of PEG molecule attachment.

Amino Acid Sequence↗
PubMed1999

Cytomegalovirus colitis in individuals without apparent cause of immunodeficiency.

Cytomegalovirus infection is usually reported in immunocompromised patients. In this study, apparently immunocompetent patients with cytomegaloviral colitis were reviewed. Records with a diagnosis of cytomegaloviral colitis from January 1989 to June 1996 were retrieved for analysis. Ten patients were included (median age 70 yr). The major presenting symptoms were diarrhea and hematochezia. Ulceration was the main macroscopic finding. Rectal bleeding was mostly self-limiting. Three patients developed local complications (rectovaginal fistula in two; rectal stricture in one). In the two patients with rectovaginal fistula, lymphocytes subsets and proliferative response were entirely normal. In the other patient, low B lymphocyte count and low response to mitogen were demonstrated. However, the immunoglobulins were not suppressed and rectal biopsies revealed noncaseating granulomas, suggesting activated cell-mediated immunity. In conclusion, a high index of suspicion is crucial for early diagnosis of cytomegaloviral colitis in patients with bloody diarrhea, even though obvious evidence of immunodeficiency is lacking.

Aged↗
PubMed1999

Three Hong Kong Chinese cases of pretibial epidermolysis bullosa: a genodermatosis that can masquerade as an acquired inflammatory disease.

Three patients in two families presented with many years' history of fragile skin, blisters, erosions and scars affecting almost exclusively the shin areas, accompanied by a variable degree of itching. Two of the patients also had toenail dystrophy. Skin biopsy revealed dermal-epidermal blister formation and milia but no immunohistochemical evidence of immunoglobulin or complement deposition. Electron microscopic study of the lesional and perilesional skin showed very sparse or absent anchoring fibrils. Immunolabelling for type VII collagen using LH 7.2 monoclonal antibody revealed a bright, linear staining pattern at the dermal-epidermal junction. The clinicopathological features were thus compatible with pretibial epidermolysis bullosa, a subtype of dystrophic epidermolysis bullosa. Of note, the inflammatory nature of the skin lesions, and their resemblance to nodular prurigo and hypertrophic lichen planus, had caused diagnostic difficulties in all cases in the past. A high degree of awareness of this rare subtype of epidermolysis bullosa is important to establish the correct diagnosis, to allow for genetic counselling and to plan clinical management.

Adolescent↗
PubMed1999

Preparation and characterization of polyethylene-glycol-modified salmon calcitonins.

The conjugation of salmon calcitonin (sCT) by covalent linkage of polyethylene glycol (PEG) was attempted to overcome several disadvantages of sCT as a therapeutic drug, namely its rapid clearance from blood circulation and enzymatic degradation. The polymer employed was succinimidyl carbonate monomethoxypolyethylene glycol (12 kDa). Superose HR size-exclusion chromatography was applied to separate the PEGylated sCTs (mono-PEG-sCT and di-PEG-sCT) from the unmodified sCT. The PEGylation of sCT was verified by an electrophoresis gel stained with iodine and by MALDI-TOF mass spectrometry. The molecular weights of mono-PEG-sCT and di-PEG-sCT were determined to be 16,094 and 29,077 Da, respectively. PEGylated sCTs showed a substantially improved stability in rat liver homogenates as compared to the intact sCT, indicating that PEG molecules protected sCT from various degrading enzymes. These PEGylated sCTs exhibited similar biological activity to the intact sCT by adenosine cyclic 3',5'-phosphate (cAMP) assay. In clearance studies in the rat, PEGylated sCTs had significantly longer circulating half-lives than the intact sCT (11.2 min for mono-PEG-sCT and 54.0 min for di-PEG-sCT versus 4.7 min for intact sCT).

Amino Acid Sequence↗
PubMed1999

Screening for the Gly40Ser mutation in the glucagon receptor gene among patients with type 2 diabetes or essential hypertension in Taiwan.

As a major counterregulatory hormone of insulin, glucagon plays an important role in regulating glucose homeostasis through its binding to the glucagon receptor. Recently a missense mutation in the glucagon-receptor gene (Gly40Ser) was found to be associated with type 2 diabetes in France and Sardinia, with a frequency as high as 4.6% and 8.3%, respectively. This mutation was also found to be associated with essential hypertension in the white population with a frequency of 5.4%. To investigate the role of this mutation in the pathogenesis of type 2 diabetes and essential hypertension in Taiwanese population, we screened 121 normal controls, 213 unrelated subjects with type 2 diabetes, and 107 unrelated subjects with essential hypertension by use of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). None of the Taiwanese subjects recruited in the study had this receptor mutation. Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.

Amino Acid Substitution↗
PubMed1999

p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding.

Aberrant expression of the alpha-fetoprotein (AFP) gene is characteristic of a majority of hepatocellular carcinoma cases and serves as a diagnostic tumor-specific marker. By dissecting regulatory mechanisms through electromobility gel shift, transient-transfection, Western blot, and in vitro transcription analyses, we find that AFP gene expression is controlled in part by mutually exclusive binding of two trans-acting factors, p53 and hepatic nuclear factor 3 (HNF-3). HNF-3 protein activates while p53 represses AFP transcription through sequence-specific binding within the previously identified AFP developmental repressor domain. A single mutation within the DNA binding domain of p53 protein or a mutation of the p53 DNA binding element within the AFP developmental repressor eliminates p53-repressive effects in both transient-transfection and cell-free expression systems. Coexpression of p300 histone acetyltransferase, which has been shown to acetylate p53 and increase specific DNA binding, amplifies the p53-mediated repression. Western blot analysis of proteins present in developmentally staged, liver nuclear extracts reveal a one-to-one correlation between activation of p53 protein and repression of AFP during hepatic development. Induction of p53 in response to actinomycin D or hypoxic stress decreases AFP expression. Studies in fibroblast cells lacking HNF-3 further support a model for p53-mediated repression that is both passive through displacement of a tissue-specific activating factor and active in the presence of tissue-specific corepressors. This mechanism for p53-mediated repression of AFP gene expression may be active during hepatic differentiation and lost in the process of tumorigenesis.

Animals↗
PubMed1999

Laryngeal pathology in the acquired immunodeficiency syndrome: diagnostic and therapeutic dilemmas.

The acquired immunodeficiency syndrome has produced a growing population of patients who, because of their associated immune system compromise, are prone to opportunistic infections and neoplastic diseases. The larynx, with its relatively inaccessible yet critical anatomic location, is a site in which these processes can produce clinical dilemmas, with respect to diagnosis as well as to therapy. By presenting 4 cases involving unusual laryngeal problems in patients infected with the human immunodeficiency virus (HIV), we emphasize these inherent diagnostic and therapeutic problems. Otolaryngologists must be familiar with the many diagnostic possibilities and therapeutic alternatives when HIV-infected patients present with laryngeal complaints.

AIDS-Related Opportunistic Infections↗
PubMed1999

Tentorial meningioma encroaching the transverse sinuses and sigmoid sinus junction area associated with dural arteriovenous fistulous malformation: a case report.

A 62-year-old woman was evaluated for tinnitis and headache. Magnetic resonance imaging and angiography revealed the coexistence of a tentorial tumor encroaching the junction of the right transverse-sigmoid sinuses, and dural arteriovenous fistulous malformation (AVFM) of the right transverse sinus. AVFM was not manipulated at all during the surgery. The pathology was fibroblastic meningioma. Postoperatively, the dural AVFM completely disappeared on follow-up angiography. The fistulas were occluded also after surgery, even though there was no manipulation of the AVFM. It is suggested that the right dominant transverse-sigmoid sinuses are partially occluded by tentorial meningioma, developing the dural arteriovenous fistula of the right transverse sinus. An acquired origin of the dural AVFM was suggested in this case.

Arteriovenous Malformations↗
PubMed1999

Limited joint mobility in diabetes.

Cheiroarthropathy is a syndrome usually associated with diabetes mellitus that involves mainly the small joints of the hand. It is generally painless and seldom treated until hand deformity is severe enough to interfere with daily life. Because cheiroarthropathy is correlated with microvascular complications of diabetes, patients with hand symptoms should be carefully investigated for neuropathy, retinopathy, and nephropathy. Improved control of diabetes is the cornerstone of management, but surgery and corticosteroid injection may alleviate severe symptoms in some patients.

Contracture↗
PubMed1999

Primary non-Hodgkin's lymphoma of the breast: breast conservation therapy in two patients.

We report two patients with primary non-Hodgkin's lymphoma of the breast who were treated with breast conservation therapy. These two patients were diagnosed with primary breast lymphoma by fine-needle aspiration cytology and underwent tumorectomy followed by adjuvant chemoradiation therapy. Follow-up studies showed that the two patients were free of disease for two and three years, respectively. To date, there exists no therapeutic standard for this disease and there is no survival advantage for patients who undergo radical mastectomy. Despite the rarity of lymphoma in the breast, a preoperative accurate diagnosis is essential so that unnecessary, extended breast ablation or delayed treatment is avoided. Cytologic diagnosis of breast lymphoma is an easy procedure and provides guidance for appropriate preoperative management. Early diagnosis combined with breast conservation therapy and systemic adjuvant therapy results in a favorable outcome for patients with breast lymphoma.

Adult↗
PubMed1999

Presence of donor- and recipient-derived DNA in cell-free urine samples of renal transplantation recipients: urinary DNA chimerism.

BACKGROUND: Previous studies have indicated that microchimerism is present in body tissues, peripheral blood, and plasma of recipients after organ transplantation. We hypothesize that donor-derived DNA may also be present in cell-free urine of renal transplant recipients and that the concentrations of urine DNA may be correlated with graft rejection. METHODS: Thirty-one female patients who had renal transplantation were enrolled in the study. In women with male organ donors, the SRY gene on the Y chromosome was used as a marker for donor-derived DNA. Real-time quantitative PCR for the SRY and beta-globin genes was carried out on cell-free urinary DNA from these patients. Serial urine samples from a female renal transplant recipient undergoing an acute rejection episode were also collected and analyzed with the beta-globin quantitative PCR system. RESULTS: SRY sequences were detected in the urine of 14 of 17 female patients with male organ donors. None of the 14 patients with female organ donors had detectable SRY sequences in urinary DNA. The median fractional concentration of donor-derived DNA was 8.7% (interquartile range, 1.9-26.4%). During the acute rejection episode, urinary concentrations of the beta-globin gene were markedly increased, with the concentrations returning rapidly to normal following antirejection treatment. CONCLUSIONS: Our results demonstrate that urinary DNA chimerism is present following renal transplantation. The measurement of urinary DNA using quantitative PCR may be useful for the diagnosis and monitoring of graft rejection.

Biomarkers↗
PubMed1998

Formation of high axial ratio microstructures from peptides modified with glutamic acid dialkyl amides.

A growing number of amphiphiles are known to form high axial ratio microstructures (HARMs) such as the hollow cylindrical microstructures called lipid tubules. As a prelude to exploring the potential of HARMs formed from lipopeptides in controlled release drug delivery, several microstructure formation conditions were investigated. We report the preparation of several glutamic acid dialkyl amides with varying alkyl chain lengths bearing a verity of peptides (1-4 amino acids) [peptide-Glu-(NHCnH2n+1)2, n=12, 14, 16]. These surfactants have been rapidly and efficiently converted into HARMs in aqueous buffer at physiological pH and ionic strength, or in buffer containing MeOH or EtOH. Helical ribbons and tubular HARMs were produced that were stable for as long as 6 months below the phase transition temperatures of the compounds. To estimate the stability of HARMs in vivo, HARMs formed from (Pro)3-Glu(NHC16H33)2 were incubated with DOPC liposomes or fetal calf serum at 40 degreesC. HARM size and shape did not change significantly, suggesting that such lipopeptide particles can retain their morphology long enough in vivo to be useful as drug delivery vehicles.

Amides↗
PubMed1998

Purification of Sepharose-unbinding ricin from castor beans (Ricinus communis) by hydroxyapatite chromatography.

Sepharose-unbinding ricin was one-step separated and purified from a crude extract of castor beans (Ricinus communis) by affinity chromatography on hydroxyapatite. This purification method does not require the time-consuming and complicated steps, such as gel filtration and ion-exchange chromatography, that have been essential in the separation of Sepharose-unbinding toxins. Using this method, approximately 180 mg of ricin was obtained from 100 g of castor beans using a bed volume of 80 ml on a hydroxyapatite column. Weak affinity of the ricin on Sepharose was confirmed and compared with Sepharose-binding ricin (ricin D), using radioiodinated ricins. The molecular mass of the ricin was estimated to be 62 kDa by 10% SDS-PAGE under nonreducing conditions. Under reducing conditions, the purified ricin appeared to be two subunits, corresponding to the molecular masses of 30 and 32 kDa. The pI value was determined to be approximately 8.9 for the ricin. Uptake of the ricin by HeLa cells was measured as almost half of ricin D uptake. Similar results were observed on CEM cells as well. In vitro cytotoxicity of ricins on different cell lines was measured by the MTT method. When compared with ricin D, the purified ricin showed approximately 10-fold less cytotoxicity to HUT78 or K562 cells and 30-fold less toxicity to CEM cells. This lower cytotoxicity of the ricin may be due to its lower cell-binding properties as evidenced by its low affinity for the cell surfaces. From these results, the purified ricin was considered to be ricin E.

Ricinus communis↗