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Biomedical subjects

D S Chi

Publications and source records attributed to D S Chi.

At least 37 records · Page 2Linked to original sources

Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease.

Endothelial cells, by virtue of their capacity to express adhesion molecules and cytokines, are intricately involved in inflammatory processes. Endothelial cells have been shown to express interleukin-1 (IL-1), IL-5, IL-6, IL-8, IL-11, IL-15, several colony-stimulating factors (CSF), granulocyte-CSF (G-CSF), macrophage CSF (M-CSF) and granulocyte-macrophage CSF (GM-CSF), and the chemokines, monocyte chemotactic protein-1 (MCP-1), RANTES, and growth-related oncogene protein-alpha (GRO-alpha). IL-1 and tumor necrosis factor-alpha (TNF-alpha) produced by infiltrating inflammatory cells can induce endothelial cells to express several of these cytokines as well as adhesion molecules. Induction of these cytokines in endothelial cells has been demonstrated by such diverse processes as hypoxia and bacterial infection. Recent studies have demonstrated that adhesive interactions between endothelial cells and recruited inflammatory cells can also signal the secretion of inflammatory cytokines. This cross-talk between inflammatory cells and the endothelium may be critical to the development of chronic inflammatory states. Endothelial-derived cytokines may be involved in hematopoiesis, cellular chemotaxis and recruitment, bone resorption, coagulation, and the acute-phase protein synthesis. As many of these processes are critical to the maturation of an inflammatory and reparative state, it appears likely that endothelial-derived cytokines play a crucial role in several diseases, including atherosclerosis, graft rejection, asthma, vasculitis, and sepsis. Genetic and pharmacologic manipulation of endothelial-derived cytokines provides an additional approach to the management of chronic inflammatory diseases.

Arteriosclerosis↗

Laparoscopy in gynecologic malignancies.

One of the cornerstones of gynecologic cancer surgery is the assessment and removal of the retroperitoneal lymph nodes. Numerous reports have demonstrated that, when performed by highly skilled individuals, laparoscopic lymphadenectomies can be performed safely. This has led to the investigation of laparoscopy in the surgical staging and treatment of patients with ovarian, cervical, and endometrial cancers. This very promising approach has the potential to revolutionize numerous aspects of the management of gynecologic malignancies. However, it must be emphasized that the use of laparoscopy for gynecologic malignancies is still in its infancy. Studies that provide complication rates and long-term results are just beginning to be reported. More clinical data are necessary before the laparoscopic techniques are accepted as new surgical standards. Ongoing, prospective clinical trials will help answer many of the questions regarding the safety and efficacy of gynecologic laparoscopy. Until more data accumulate, operative laparoscopy will remain a promising, but unproven, tool in the management of patients with gynecologic malignancies.

Endometrial Neoplasms↗

Primary intravenous paclitaxel and platinum chemotherapy for high-risk Stage I epithelial ovarian carcinoma.

OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of all patients with Stage I ovarian cancer treated at our institution between March 1993 and June 1995. RESULTS: Twenty patients received adjuvant paclitaxel-containing chemotherapy for Stage I ovarian carcinoma after comprehensive surgical staging. Five patients (25%) had Stage IA disease and 15 patients (75%) had Stage IC disease. Tumor grades were: 1, five patients (25%); 2, nine patients (45%); and 3, six patients (30%). Histologic cell types were: clear-cell, ten (50%); endometrioid, five (25%); mucinous, three (15%); and serous, two (10%). Nineteen patients (95%) were treated with i.v. paclitaxel and platinum chemotherapy. One patient (5%) received i.v. paclitaxel alone. Eighteen patients (90%) had five cycles of chemotherapy, while two patients (10%) had three. The 96 total cycles were associated with nine episodes (9%) of significant toxicity: fever, four (4%); severe nausea and vomiting, two (2%); Clostridium difficile enteritis, one (1%); congestive heart failure, one (1%); and anemia, requiring blood transfusion, one (1%). With a median follow-up of 36 months (range 24-50 mos), all 20 patients are alive, and 19 (95%) are disease-free. The one patient (5%) treated with i.v.++paclitaxel alone developed an abdominal recurrence 22 months after diagnosis. CONCLUSION: Primary i.v.++paclitaxel and platinum chemotherapy in patients with high-risk Stage I epithelial ovarian carcinoma is reasonably well tolerated and may improve survival. Larger studies with long-term follow-up are needed.

Adenocarcinoma↗

Multifunctional cytokine expression by human coronary endothelium and regulation by monokines and glucocorticoids.

Human endothelium is capable of expressing a variety of molecules, including cytokines and growth factors, critical to inflammation. This aspect of coronary endothelium has not been studied in detail. In this study, we report, for the first time, expression of multifunctional cytokines by human coronary artery endothelial cells (HCAEC) and their regulation by inflammatory cytokines and glucocorticoids. We also compared expression of cytokine transcripts in two additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP-1 was seen following treatment with TNFalpha. We found no expression of IL-1RA, IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glucocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation.

Cell Line↗

Identification of H. pylori in saliva by a nested PCR assay derived from a newly cloned DNA probe.

A novel probe was developed from genomic DNA of Helicobacter pylori ATCC type strain 43629. It hybridized with all 73 H. pylori clinical isolates tested but not with any of 183 non-H. pylori DNAs in dot blot hybridization. Typing tests revealed 41 different HaeIII-digestion patterns from 57 H. pylori strains tested. Based on the sequence of the probe, a nested PCR was developed that detected as little as 2 fg of H. pylori DNA or approximately equivalent to one cell. No PCR products were amplified from any of 21 non-H. pylori strains tested. Using this nested PCR, H. pylori DNA was detected in 33 of 45 (73%) saliva samples collected from patients with gastric H. pylori infection. These data suggest that the probe is useful for typing H. pylori and that the nested PCR is a valuable tool for detecting H. pylori DNA in saliva.

DNA Fingerprinting↗

The role of surgery in the management of ovarian cancer: primary and interval cytoreductive surgery.

Ovarian cancer remains the number one cause of mortality in gynecologic malignancies and the fifth most common cause of death among all malignancies in women. Unfortunately, recent data confirm that only approximately 90% of "apparent" early ovarian cancer are inadequately staged, and only approximately 80% of patients with advanced-stage disease are adequately staged. Interval debulking surgery, a newer treatment modality, appears to have a promising role for patients who cannot be adequately debulked at their initial surgery. Second-look laparotomy continues to be the most accurate way to document responses to chemotherapy in protocol settings, but additional clinical trials with newer second-line chemotherapy will be necessary before definitive statements can be made with regard to survival advantages in patients who undergo second-look laparotomy.

Clinical Trials as Topic↗

The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma.

Thirty-eight patients with Stage I and II uterine carcinosarcoma were treated by surgery with and without whole-pelvic irradiation (WPI) at our institution from 1975 to 1993. Ten patients (8 Stage I and 2 Stage II) were treated with surgery alone, while 28 patients (20 Stage I and 8 Stage II) received WPI in addition to surgery. With a median follow-up of 75 months (range 25-220 months), a trend toward a decreased rate of pelvic recurrence in those receiving WPI (6/28, 21%) compared to those treated with surgery alone (5/10, 50%) was observed (P = 0.09). There was no difference in the rate of distant recurrence between those receiving WPI (12/28, 43%) and those who did not (4/10, 40%) (P = 0.9). There was also no difference in the 2- and 5-year Kaplan-Meier survival estimates for the patients receiving WPI (79 and 59%, respectively) compared to those who did not receive WPI (60 and 60%, respectively) (P = 0.84). In this small series, the addition of whole-pelvic irradiation to primary surgery did not improve survival; however, a trend toward improved pelvic control was observed, suggesting a possible benefit for pelvic irradiation that should be studied in future trials.

Aged↗

Hepatic resection for metastatic gynecologic carcinomas.

OBJECTIVE: To report a series of cases of hepatic resection for metastatic gynecologic carcinomas. METHODS: We reviewed the records of all patients who underwent hepatic resection for metachronous liver metastases from gynecologic carcinomas at our institution from 1986 to 1996. RESULTS: Twelve patients were identified with a median age of 60 years (range 30-73 years). The primary sites of carcinoma were as follows: ovary, 7 (58%); cervix, 2 (17%); endometrium, 2 (17%); and fallopian tube, 1 (8%). The median disease-free interval before the diagnosis of liver metastasis was 32 months (range 1-243 months). The types of liver resections were as follows: trisegmentectomy, 4 (33%); lobectomy, 4 (33%); segmentectomy, 3 (25%); and wedge resection, 1 (8%). To remove all visible tumor with adequate margins, additional surgery included the following: resection of a portion of the diaphragm, 5 (42%); wedge resection of the right lung, 3 (25%); resection of a portion of the pericardium, 2 (17%); and adrenalectomy, 1 (8%). One patient (8%) had pulmonary wedge resections of bilateral pulmonary metastases. There was no perioperative mortality. Ten patients (83%) received additional chemotherapy. With a median follow-up of 25 months (range 8-94 months), the median survival time is 27 months. Three patients (25%) have no evidence of tumor recurrence at 8, 17, and 38 months of follow-up. Nine patients (75%) have had tumor recurrence at a median of 12 months from the time of surgery. CONCLUSIONS: Hepatic resection of metachronous metastases from gynecologic carcinomas can be performed safely and may help prolong survival in carefully selected patients.

Adult↗

The role of surgical cytoreduction in Stage IV endometrial carcinoma.

OBJECTIVE: To evaluate the impact of surgical cytoreduction in patients (pts) with Stage IV endometrial adenocarcinoma. METHODS: We performed a retrospective chart review of all pts with Stage IV endometrial carcinoma treated at our institution from January, 1977, to February, 1995. RESULTS: Fifty-five patients who underwent surgery as part of their primary treatment for Stage IV endometrial carcinoma were identified. They were divided into three groups: Group I consisted of 24 pts (44%) who underwent optimal surgical cytoreduction (diameter of largest residual tumor nodule < or = 2 cm); Group II contained 21 pts (38%) who underwent suboptimal surgical cytoreduction (> 2 cm residual disease); Group III consisted of 10 pts (18%) who had unresectable carcinomatosis and had no cytoreduction at all. There were no statistically significant differences between the three groups with respect to median age at diagnosis, tumor grade, histologic subtype, or the presence of extra-abdominal metastases. The median survival rates for the three groups were I, 31 months; II, 12 months; and III, 3 months (P < 0.01). Within Group I, there was no statistically significant difference in survival between the 8 pts who were found at laparotomy to have metastatic disease < or = 2 cm and the 16 pts who initially had metastatic disease > 2 cm and were subsequently cytoreduced to optimal status. On multivariate analysis only the extent of surgical cytoreduction had prognostic significance on survival. CONCLUSION: The prognosis of Stage IV endometrial carcinoma is poor. However, the data in this series suggest that aggressive tumor cytoreduction may improve survival in these patients.

Adenocarcinoma↗

Differentiation of Helicobacter pylori strains directly from gastric biopsy specimens by PCR-based restriction fragment length polymorphism analysis without culture.

Recent studies have shown the usefulness of PCR-based restriction fragment length polymorphism (RFLP) analysis for differentiating Helicobacter pylori strains isolated by culture. For this study, a PCR-based RFLP assay was developed for directly typing H. pylori strains from gastric biopsy specimens. Nineteen gastric biopsy specimens obtained from patients undergoing endoscopy for gastrointestinal complaints were cultured for isolation of H. pylori. Genomic DNA preparations from these gastric biopsy specimens and the corresponding H. pylori isolates were tested by our PCR-based RFLP assay. The 1,179-bp H. pylori DNA fragments amplified by the PCR assay were digested with the restriction enzymes HhaI, MboI, and AluI and analyzed by agarose gel electrophoresis. HhaI, MboI, and AluI digestion produced 11, 10, and 6 distinguishable digestion patterns, respectively, from the 19 H. pylori isolates tested and generated 13, 11, and 6 different patterns, respectively, from the 19 gastric biopsy specimens. The patterns from 13 of the 19 gastric biopsy specimens matched those of the H. pylori isolates from the corresponding patients. The patterns from the remaining six biopsy specimens appeared to represent infection by two strains of H. pylori; the pattern of one strain was identical to that of the isolate from the corresponding patient. By combining all the restriction enzyme digestion patterns obtained by using HhaI, MboI, and AluI, we observed 19 distinct RFLP patterns from the 19 specimens. The results suggest that the PCR-based RFLP analysis method may be useful as a primary technique to identify and distinguish H. pylori strains directly from gastric biopsy specimens without culture of the organisms.

Bacterial Typing Techniques↗

A newly developed PCR assay of H. pylori in gastric biopsy, saliva, and feces. Evidence of high prevalence of H. pylori in saliva supports oral transmission.

We have recently developed a new PCR assay for the detection of H. pylori. In this study, the polymerase chain reaction (PCR) assay was used to detect H. pylori in 88 gastric biopsy, 85 saliva, and 71 fecal specimens from 88 patients. H. pylori infection was confirmed in 71 of 88 patients by culture and/or histological stain of gastric biopsies. Serum IgG antibody to H. pylori was also measured and resulted in 97% sensitivity and 94% specificity. H. pylori DNA was detected by the PCR assay in gastric biopsy specimens from all 71 patients (100% sensitivity) with proven gastric H. pylori infection but not from 17 noninfected patients (100% specificity). In saliva specimens, H. pylori DNA was identified in 57 of the 68 patients (84%) with proven gastric H. pylori infection and in three of the 17 patients without gastric H. pylori infection. However, the PCR assay was only able to detect H. pylori DNA in the feces from 15 of 61 patients (25%) with proven gastric H. pylori infection and one of the 10 patients without gastric H. pylori infection. The results show that the PCR assay is reliable for detecting the presence of H. pylori in gastric biopsy and saliva specimens. The data indicate that H. pylori exists in a higher prevalence in saliva than feces and that the fecal-oral route may be an important means of transmission of this infection in developing countries but not as significant as previously suspected in the developed countries. It is likely that the oral-oral route is more prominent.

Antibodies, Bacterial↗

Lymphoblastoid interferon-alpha inhibits T cell proliferation and expression of eosinophil-activating cytokines.

T cell-derived cytokines, such as interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) activate eosinophils, whereas other cytokines, such as tumor necrosis factor (TNF)-alpha and IL-13, determine eosinophil recruitment. Interferon-alpha (IFN-alpha), a leukocyte-derived cytokine, has been shown to have beneficial effects in eosinophil-mediated disorders, such as the hypereosinophilic syndrome and a murine model of allergic asthma, where it inhibited eosinophil recruitment. We tested the hypothesis that IFN-alpha acted in eosinophil-mediated disorders by modulating T cell cytokine expression. Peripheral blood mononuclear cells (PBMC) or human ragweed-specific TH1 (2B8) and TH2 (2D2) T cell clones were cultured in the presence of 5 micrograms/ml of phytohemagglutinin (PHA) or 25 micrograms/ml of antigen Amb a 1 (short ragweed allergen), respectively, and lymphoblastoid IFN-alpha (varying from 0 to 10,000 U/ml). We assessed T cell proliferation by [3H]thymidine incorporation and production of IL-5 and GM-CSF by ELISA. Expression of cytokine transcripts was analyzed by the reverse transcription-polymerase chain reaction technique (RT-PCR). IFN-alpha induced a dose-dependent suppression of T cell proliferation of both PBMC (p < 0.001) and the T cell clones (p < 0.001). IFN-alpha inhibited gene expression of IL-5, GM-CSF, TNF-alpha, and IL-13 in PBMC. Furthermore, IFN-alpha significantly inhibited mitogen-induced and antigen-induced production of IL-5 and GM-CSF. IFN-alpha may benefit eosinophil-mediated disorders by inhibiting T cell function and production of cytokines active on human eosinophils.

Adult↗

Resolution of the neutropenia of Felty's syndrome by longterm administration of recombinant granulocyte colony stimulating factor.

Felty's syndrome is characterized by neutropenia, splenomegaly, and recurrent infection in patients with rheumatoid arthritis. We used recombinant granulocyte colony stimulating factor (rGCSF) in a patient with Felty's syndrome and recurrent sepsis. rGCSF induced a statistically significant increase in the patient's absolute neutrophil and total white blood cell counts. During 14 months of followup taking rGCSF, disseminated varicella zoster was the only infectious complication. Except mild thrombocytopenia and a transient flare of arthritis, no serious adverse effects occurred. rGCSF may be a safe and effective therapy for Felty's syndrome in selected patients.

Aged↗

Effect of interferon alpha on HLA-DR expression by human buccal epithelial cells.

/We have studied the effect of interferon alpha (IFN-alpha) on MHC class II expression by human buccal epithelial cells (BEC), and mRNA expression by BEC and mucosal-associated mononuclear cells (MAMC). In 6 experiments, freshly collected BEC were suspended at a concentration of 1.0 x 10(5)/ml in RPMI 1640 and incubated in the presence of 0-10,000 IU/ml of human lymphoblastoid IFN-alpha (HuIFN-alpha). Zero and six hour samples were analyzed by single color flow cytometry using FITC-labeled murine IgG1 monoclonal antibody to HLA-DR. Preparations were also analyzed for expression of cytokine transcripts (IL-2, IL-4, IL-5, IL-6, IL-8, IFN-gamma, GM-CSF) by reverse transcriptase polymerase chain reaction (RT-PCR). Increasing concentrations of IFN-alpha resulted in proportionate increases in the percentage of HLA-DR + BEC (r = 0.7897, p = 0.0627) and in the percentage of HLA-DR+ staining at higher intensities (10(1) to 10(2) log fluorescence intensity) (LFI) (r = 0.4010, p = 0.0424). The percentage of HLA-DR + BEC rose from a mean of 1.5% with no IFN-alpha to 7% with 10,000 IU/ml IFN-alpha (p < 0.05). The percentage of HLA-DR + BEC staining at 10(1) to 10(2) LFI rose from a mean of 8.3% with no added IFN-alpha to 19.2% with 10,000 IU/ml IFN-alpha (p < 0.05). Unstimulated BEC constitutively expressed IL-8 and GM-CSF. IFN-alpha stimulated preparations also expressed IFN-gamma, possibly due to the presence of MAMC, which comprised 2-9% of the total cell population. These data indicated that HuIFN-alpha upregulates MHC class II expression by human BEC, possibly by enhancing IFN-gamma production by MAMC present in the culture preparations.

Cells, Cultured↗

Laparoscopic management of adnexal masses in women with a history of nongynecologic malignancy.

OBJECTIVE: To describe the safety and efficacy of laparoscopy in the diagnosis and treatment of patients with a history of nongynecologic malignancy presenting with an adnexal mass. METHODS: A retrospective review of the records of all patients with a history of nongynecologic malignancy who underwent laparoscopy for adnexal masses at our institution in 1992-1994. RESULTS: Thirty-four patients were identified. The mean age was 57.3 years (range 32-85). Twenty-five had breast cancer, three had malignant melanoma, and two had lymphoma; the remaining four had lung, colon, stomach, and pancreatic cancer, respectively. Thirty of the 34 cases (88%) were managed laparoscopically; unilateral or bilateral salpingo-oophorectomy was performed in 22, laparoscopically assisted vaginal hysterectomy in three, ovarian cystectomy in three, and pelvic washings in two. In these cases, the adnexal disease was benign in 24 and metastatic cancer in six. In all the metastatic cases, preoperative ultrasound or computed tomography scan revealed complex and/or solid adnexal masses. Six complications occurred in the 34 cases; two of 25 patients who had D&C had uterine perforation, two patients had subcutaneous hematomas at laparoscopic puncture sites, one had a bowel obstruction, and one developed pneumonia after laparotomy. CONCLUSION: Laparoscopy proved to be safe and effective in the initial surgical evaluation of patients with a history of a nongynecologic malignancy presenting with an adnexal mass. Most patients can be spared the added morbidity and convalescence associated with laparotomy. This laparoscopic approach should be considered the initial method of surgical evaluation in this population.

Adnexal Diseases↗

High prevalence of Helicobacter pylori in saliva demonstrated by a novel PCR assay.

AIMS: To investigate the prevalence of Helicobacter pylori in the saliva of patients infected with this bacterium. METHODS: A novel polymerase chain reaction (PCR) assay was developed to detect H pylori in saliva and gastric biopsy specimens from patients undergoing endoscopy. RESULTS: Our PCR assay amplified a 417 base pair fragment of DNA from all 21 DNAs derived from H pylori clinical isolates but did not amplify DNA from 23 non-H pylori strains. Sixty three frozen gastric biopsy and 56 saliva specimens were tested. H pylori specific DNA was detected by PCR in all 39 culture positive biopsy specimens and was also identified from another seven biopsy specimens which were negative by culture but positive by histology. H pylori specific DNA was identified by PCR in saliva specimens from 30 (75%) of 40 patients with H pylori infection demonstrated by culture or histological examination, or both, and in three patients without H pylori infection in the stomach. CONCLUSION: The results indicate that the oral cavity harbours H pylori and may be the source of infection and transmission.

Base Sequence↗

Serum ionized magnesium levels during intravenous MGSO4 therapy of preeclamptic women.

Using a novel ion-selective electrode, we have shown that there is over a 100% increase in venous serum levels of ionized Mg during intravenous MgSO4 therapy of preeclamptic patients. By 6 hours of therapy, the range is 0.92-1.65 mmol/l (95% C.I.). There are strong correlations between levels of ionized and total Mg throughout therapy (r = 0.92-0.95, p < 0.01).

Adult↗