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Biomedical subjects

L Kong

Publications and source records attributed to L Kong.

At least 55 records · Page 3Linked to original sources
PubMed1998

Bcl-2 family expression in salivary glands from patients with primary Sjögren's syndrome: involvement of Bax in salivary gland destruction.

To investigate the molecular mechanism of glandular parenchyma destruction in Sjögren's syndrome (SS), Bcl-2, Bax, Bcl-X, and Bak expression were studied. SS (n = 18) and control salivary glands (n = 6) were examined by immunohistochemistry. Apoptosis was assessed by in situ DNA nick end labeling. Infiltrating mononuclear cells in the SS salivary gland showed elevated Bcl-2. These mononuclear cells expressed increased Bax but did not undergo apoptosis. Both SS and control salivary gland ductal epithelial cells expressed Bcl-2, Bax, and Bcl-X. SS, but not normal, salivary gland acinar cells expressed Bax and underwent apoptosis. These results suggest that elevated Bax expression in SS salivary gland acinar cells may play an important role in the apoptotic pathway. In contrast, Bcl-2 expression in SS infiltrating mononuclear cells and ductal cells may contribute to their survival.

Apoptosis↗
PubMed1998

Single-stage, bilateral, video-assisted thoracoscopic lung volume reduction surgery for end-stage emphysema.

The reintroduction of lung volume reduction surgery has provided functional improvement for selected patients afflicted with end-stage emphysema. Evolution of the operation from a median sternotomy approach to the two-stage video-assisted thoracoscopic surgical technique in our experience has resulted in a faster return to full activity. Nineteen patients underwent video-assisted thoracoscopic lung volume reduction surgery between July 1995 and August 1997. The 12 men and 7 women in the study had an average age of 63.7 years. All patients were evaluated preoperatively with computed tomography of the chest, radionuclide lung perfusion scan, left ventricular stress test, right heart catheterization, and a monitored rehabilitation program. In 15 patients the operation was performed as a bilateral single-stage procedure. The operation involved resection of wedges from the upper lobes and in 10 of these patients from the lower lobes as well. In all patients the estimated operative blood loss was less than 150 ml. The mean operative time was 177 minutes (range 115-235 minutes). The mean length of hospital stay was 10.8 days (median 11 days, range 5-24 days). At 2 to 3 months' follow-up increases were noted in the FEV1 (51%), PaO2 (27%), and 6-minute walk distance (18%); and there was a decrease in total lung capacity and respiratory volume. No significant change was observed in carbon monoxide diffusion in the lung. Morbidity included persistent air leaks in three patients and refractory supraventricular tachyarrhythmia in one. There were no perioperative deaths. We therefore recommend this technical modification to reduce operating time and blood loss without compromising surgical exposure or outcome.

Endoscopy↗
PubMed1998

Fibroblast growth factor 2 control of vascular tone.

Vascular tone control is essential in blood pressure regulation, shock, ischemia-reperfusion, inflammation, vessel injury/repair, wound healing, temperature regulation, digestion, exercise physiology, and metabolism. Here we show that a well-known growth factor, FGF2, long thought to be involved in many developmental and homeostatic processes, including growth of the tissue layers of vessel walls, functions in vascular tone control. Fgf2 knockout mice are morphologically normal and display decreased vascular smooth muscle contractility, low blood pressure and thrombocytosis. Following intra-arterial mechanical injury, FGF2-deficient vessels undergo a normal hyperplastic response. These results force us to reconsider the function of FGF2 in vascular development and homeostasis in terms of vascular tone control.

Animals↗
PubMed1998

Incidence and outcome of Staphylococcus aureus bacteremia in hemodialysis patients.

BACKGROUND: Staphylococcus aureus bacteremia is frequently associated with metastatic complications and infective endocarditis (IE). The Duke criteria for the diagnosis of IE utilize echocardiographic techniques and are more sensitive than previous criteria. The documentation of IE in patients undergoing hemodialysis (HD) has become increasingly important in order to avoid the overuse of empiric vancomycin and the emergence of antibiotic resistance. METHODS: Patients who developed S. aureus bacteremia while undergoing HD at a tertiary medical center or one of four affiliated outpatient HD units were identified. Clinical outcome (death, metastatic complications, IE, and microbiologic recurrence) was assessed during hospitalization and at three months after discharge. Transthoracic and transesophageal echocardiograms were performed and the Duke criteria were used to diagnose IE. Pulse field gel electrophoresis was performed to confirm genetic similarity of recurrent isolates. RESULTS: Four hundred and forty-five patients underwent hemodialysis for 5431.8 patient-months. Sixty-two developed 65 episodes of S. aureus bacteremia (1.2 episodes/100 patient-months). Complications occurred in 27 (44%) patients. Bacteremia recurred in patients who dialyzed through polytetrafluorethylene grafts (44.4% vs. 7.1%, P = 0.0.01), and there was a trend to increased recurrence in patients who received only vancomycin (19.5% vs. 7.1%, P = 0.4). IE was diagnosed in 8 patients (12%), six of whom had normal transthoracic echocardiograms. CONCLUSIONS: Sensitive echocardiographic techniques and the Duke criteria for the diagnosis of IE should be used to determine the proper duration of antibiotic therapy in hemodialysis patients with S. aureus bacteremia. This diagnostic approach, coupled with early removal of hardware, may assist in improving outcomes.

Adult↗
PubMed1998

Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients.

To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.

Algorithms↗
PubMed1998

Opening blood-brain-barrier by intracarotid infusion of papaverine in treatment of malignant cerebral glioma.

OBJECTIVE: To find an effective method for the treatment of malignant cerebral glioma by opening the blood-brain-barrier (BBB). METHODS: The concentration of methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and 155 patients with malignant glioma were treated by intracarotid infusion of papaverine and Bis-chloronitrosourea (BCNU). RESULTS: After intracarotid infusion of papaverine for reversible opening of BBB, the MTX concentration in tumor tissue was 1810 +/- 380 ng/g, higher than that in patients without papaverine infusion (997 +/- 126 ng/g). Eighty-nine patients with glioblastoma and 66 patients with anaplastic astrocytoma received intracarotid infusion of papaverine and BCNU (250 mg) for an average of 2.14 times. The mean survival time of these patients was 114.5 weeks, median survival time was 140 weeks, and five-year survival rate was 22.97%. CONCLUSION: The combined chemotherapy with papaverine and BCNU through intra-arterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.

Adolescent↗
PubMed1998

CD4 mononuclear cell infiltrates and Fas/Fas ligand positive mammary gland cells in breast tissue from a patient with Sjögren's syndrome.

We describe a 49-year-old patient with lip biopsy proven Sjögren's syndrome (SS) and keratoconjunctivitis sicca, who had dental caries, xerostomia, recurrent upper respiratory tract infections, arthritis in her hands, elbows and knees, and recurrent parotid inflammation. She developed bilateral breast nodules in 1988. Right breast nodules were excised in 1993 and 1995, but reappeared in 1996, requiring 2 more excisions. Breast tissue samples showed remarkable intralobular and perilobular mononuclear cell infiltrates that were predominantly CD4+ T cells and expressed bcl-2. A few cells stained CD20+ and CD8+. SS breast glandular epithelial cells stained more intensely for Fas compared to normal cells. CD4+ T cells and Fas mediated cell death may be involved in the mammary gland lesions in SS.

Breast↗
PubMed1997

Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-beta1 knockout mice: MHC class II is a factor in the pathogenesis of TGF-beta1 knockout mice.

Mice homozygous for a disrupted TGF-beta1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjögren's syndrome. At 2 wk of age, these TGF-beta1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age. We studied salivary glands from symptomatic mutant mice >14 days of age. Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining. To elucidate the role of MHC class II, salivary glands from TGF-beta1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II. In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands. These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-beta1 mutant mice. Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjögren's syndrome.

Animals↗
PubMed1997

Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: To assess the role of Fas-mediated apoptosis in the salivary glands of patients with primary Sjögren's syndrome (SS). METHODS: Expression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin-dUTP). RESULTS: The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium. CONCLUSION: Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl-2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.

Apoptosis↗
PubMed1997

Melanoma cell adhesion to injured arterioles: mechanisms of stabilized tethering.

An isolated perfused vessel model was used to examine the mechanisms underlying the adhesive interactions between circulating tumor cells and subendothelial matrix in denuded arterioles. Arterioles ranging from 70 to 100 microm in diameter were isolated from rat mesentery, transferred to an isolated vessel chamber, cannulated on both ends with glass micropipettes, and perfused with media containing 10(6) hamster melanoma (RPMI 1856) cells/ml. In a second group of arterioles, the endothelium was denuded by running 2 ml of air through the vessel lumen. Since the tumor cells did not adhere to the vessel wall when perfused at physiologically relevant shear rates, perfusate flow was stopped and the tumor cells were allowed to settle onto the vessel wall for 20 min. After counting the number of tumor cells that settled onto the arteriolar wall, perfusate flow was re-initiated and unattached cells were washed away. The number of cells remaining adherent were counted and the percentage of adherent cells (relative to the total number of cells that settled on to the vessel wall during the period of no-flow) were calculated and compared among different groups. We observed that tumor cells are much more adhesive to denuded arterioles than to intact arterioles. To determine the mechanisms responsible for the adhesive interactions that become established and stabilized during the period of flow reduction, denuded arterioles were treated with fibronectin antiserum or Arg-Gly-Asp (RGD) peptides. Both treatments significantly reduced tumor cell adhesion to denuded arterioles. In subsequent studies, melanoma cells were treated with a transglutaminase inhibitor, monodansylcadaverine (MDC), which reduced the ability of adherent tumor cells to withstand the anti-adhesive effects of a subsequent increase in perfusate flow rate after the period of no-flow. Our data suggest that tumor cells adhere to fibronectin in the subendothelial matrix in denuded arterioles by an RGD-dependent mechanism. Moreover, our observations are consistent with the concept that a transglutaminase-catalysed reaction acts to stabilize the adhesive interactions between subendothelial matrix components and melanoma cells during the period of flow stasis such that the cells are able to withstand subsequent substantial increases in wall shear rate and remain adherent.

Animals↗
PubMed1997

In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743,872).

The echinocandin MK-0991, formerly L-743,872, is a water-soluble lipopeptide that has been demonstrated in preclinical studies to have potent activity against Candida spp., Aspergillus fumigatus, and Pneumocystis carinii. An extensive in vitro biological evaluation of MK-0991 was performed to better define the potential activities of this novel compound. Susceptibility testing with MK-0991 against approximately 200 clinical isolates of Candida, Cryptococcus neoformans, and Aspergillus isolates was conducted to determine MICs and minimum fungicidal concentrations MF(s). The MFC at which 90% of isolates are inhibited for 40 C. albicans clinical isolates was 0.5 microg/ml. Susceptibility testing with panels of antifungal agent-resistant species of Candida and C. neoformans isolates indicated that the MK-0991 MFCs for these isolates are comparable to those obtained for susceptible isolates. Growth kinetic studies of MK-0991 against Candida albicans and Candida tropicalis isolates showed that the compound exhibited fungicidal activity (i.e., a 99% reduction in viability) within 3 to 7 h at concentrations ranging from 0.06 to 1 microg/ml (0.25 to 4 times the MIC). Drug combination studies with MK-0991 plus amphotericin B found that this combination was not antagonistic against C. albicans, C. neoformans, or A. fumigatus in vitro. Studies with 0 to 50% pooled human or mouse serum established that fungal susceptibility to MK-0991 was not significantly influenced by the presence of human or mouse serum. Results from resistance induction studies suggested that the susceptibility of C. albicans was not altered by repeated exposure (40 passages) to MK-0991. Erythrocyte hemolysis studies with MK-0991 with washed and unwashed human or mouse erythrocytes indicated minimal hemolytic potential with this compound. These favorable results of preclinical studies support further studies with MK-0991 with humans.

Amphotericin B↗
PubMed1997

Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis.

The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated in mouse models of disseminated candidiasis, aspergillosis, and cryptococcosis. The echinocandins are potent inhibitors of 1,3-beta-D-glucan synthase. Two models of disseminated candidiasis were used. In a Candida albicans mouse survival model with both DBA/2N and CD-1 mice, estimates of the 50% effective doses (ED50s) of MK-0991 were 0.04 and 0.10 mg/kg of body weight/dose at 21 days after challenge, respectively. In a C. albicans target organ assay (TOA) with DBA/2N mice, MK-0991 at levels of > or =0.09 mg/kg/dose significantly reduced the numbers of C. albicans CFU/g of kidneys compared to the numbers in the kidneys of control mice from 1 to 28 days after challenge. Even when given as a single intraperitoneal dose either 30 min or 24 h after challenge, MK-0991 was effective and significantly reduced the numbers of C. albicans CFU/g of kidney compared to those in the controls. MK-0991 was >300-fold less active when it was administered orally than when it was administered parenterally. MK-0991 was efficacious in mouse TOAs against other C. albicans strains and Candida species including Candida tropicalis, Candida (Torulopsis) glabrata, Candida lusitaniae, Candida parapsilosis, and Candida krusei. MK-0991 was ineffective against disseminated Cryptococcus neoformans infections. In the model of disseminated aspergillosis in mice, MK-0991 at doses of > or =0.02 mg/kg/dose significantly prolonged the survival of DBA/2N mice, with estimates of the ED50 and ED90 of MK-0991 being 0.03 and 0.12 mg/kg/dose, respectively, at 28 days after challenge. MK-0991 is a potent, parenterally administered therapeutic agent against disseminated candidiasis and aspergillosis that warrants further investigation in human clinical trials.

Administration, Oral↗
PubMed1997

Evaluation of experimental therapeutics in a new mouse model of Helicobacter felis utilizing 16S rRNA polymerase chain reaction for detection.

BACKGROUND: A new mouse model of Helicobacter felis infection, which mimics the human infection observed with H. pylori, has recently been developed utilizing polymerase chain reaction (PCR) based on the 16S rRNA gene sequence for detection of infection. METHODS: We tested several therapeutic regimens in this model, including some currently utilized in the clinic and some shown ineffective in the clinic. RESULTS: The therapeutic results obtained by PCR with this model are consistent with results observed in the published human H. pylori clinical trials and also with results obtained in another H. felis mouse model utilizing culture and histology. CONCLUSIONS: These results support further use of this new model in screening for new therapeutic regimens for the management of Helicobacter disease.

Animals↗
PubMed1997

[A cytogenic study on colorectal carcinoma].

OBJECTIVE: To study the cytogenesis of colorectal carcinoma and to look for colorectal carcinoma related chromosomal fragility sites which could facilitate screening of high risk colorectal carcinoma patients. METHODS: 20 cases of surgically resected colorectal carcinomas and 4 cell lines were analysed cytogenetically. RESULTS: Most of the tumor cells were heteroploid, the chromosome number was predominately hypodiploid. Karyotypic analysis demonstrated an increase of chromosome 13, and loss of chromosome 17 and chromosome 1 appeared frequently. The most frequently found structural abnormalities in colorectal carcinoma were breakpoint 1q21 and 1p13. Highly non-random cancer chromosome breakpoints and fragile sites were compared with the oncogene locus and found that their locus or neighboring locus was 1q21. CONCLUSION: The results suggest that breakpoint 1q21 may be related to tumorgenesis and may be useful in screening and preventing colorectal carcinoma.

Adenocarcinoma↗
PubMed1997

[Treatment of congenital glaucoma with trabeculotomy].

OBJECTIVE: To investigate the method of localization of Schlemm's canal during trabeculotomy to evaluate the successful rate of trabeculotomy. METHOD: The author treated 38 cases (46 eyes) of congenital glaucoma with trabeculotomy. Harms trabeculotomy knife was introduced into the Schlemm's canal through the cutting end of an external collecting channel. The follow-up period was over 6 months in 37 eyes. RESULTS: The intraocular pressure, C/D ratio were significantly improved after surgery compared to the preoperative ones (P < 0.05). But no significant differences were found in the corneal diameter, the depth of the anterior chamber, the length of ocular axis before and after surgery (P > 0.05). The intraocular pressure of 27 eyes (73.0%) was less than or equal to 2.8 kPa (1 kPa = 7.5 mmHg), showing good control of glaucoma. CONCLUSION: During trabeculotomy, the trabeculotomy knife introduced in to the Schlemm's canal through an external collecting channel is a better and accurate method of localization of Schlemm's canal. The method is relatively simple, reliable and has certain value in clinical application.

Child↗
PubMed1997

[The changes of fibrinolysis in plasma and wounds in rats inflicted with deep partial thickness burns].

We observed the changes in wound histopathology and fibrinolysis of rats with deep partial thickness burns during 10 days after scalding in order to study the relations of early progressive damage of deep partial thickness burn wound and the healing of the wound to fibrinolysis. Using Masson's trichrome stain of collagen, we demonstrated that partial thickness burn wound progressively deteriorated within 72 hours postburn, and epidermal cells on wound edge proliferated, creeping between necrotic and residual collagen by 10th day postburn. The results of assays of fibrinolytic parameters in plasma and 24 hour exudate from wound showed that fibrinolysis activated at 2 hour postburn but had been suppressed by 24 hour postburn till last day (10 day postburn) of the observation. The analysis of dynamic changes and relations in fibrinolytic parameters revealed that the suppressive factors of fibrinolysis might be enhanced activities of PAI, alpha 2-antiplasmin and antithrombin II after injury. Results suggested that suppression of fibrinolysis might protect fibrin deposited in the wound from lysis and play an important role in early progressive deterioration of deep partial thickness burn and regulation of its healing.

Animals↗