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Biomedical subjects

C S Lee

Publications and source records attributed to C S Lee.

At least 91 records · Page 5Linked to original sources
PubMed2001

Acute diverticulitis in heart- and lung transplant patients.

Significant gastrointestinal complications have been observed in patients following heart- and lung transplantation. These complications can occur in the immediate post-operative period or remote from the time of transplantation. We retrospectively reviewed the medical records of 268 consecutive patients who received either heart- or lung transplants at Henry Ford Hospital between 1985 and 1998. Two hundred and thirty-three patients received heart transplants and 35 underwent lung transplantation. Two patients developed acute diverticulitis post transplant, both requiring surgery. Management of acute diverticulitis in the heart- and lung transplant population requires a high index of suspicion. Early and aggressive diagnosis is mandatory. Surgical intervention must be prompt when indicated, with meticulous attention to surgical technique. With appropriate intervention, reasonable outcomes can be expected.

Acute Disease↗
PubMed2001

Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest.

BACKGROUND: Because there is no smooth muscle cell surrounding the capillary endothelial cells, the effect of coronary microcirculation at the capillary level following cardioplegic arrest and reperfusion would be much different from that of resistant arterioles. We therefore studied the effect of hypothermic blood cardioplegic arrest and subsequent reperfusion on the myocardial capillaries in cardiac operation patients. METHODS: Twenty-seven patients who underwent cardiac operations were included in this study. Three sequential biopsies (preischemia, ischemia, and reperfusion) were obtained from the right atrium. This study was restricted to blood vessels with a diameter of less than 8 microns. Ten randomly selected capillaries from each biopsy were measured for luminal surface area, endothelial cytoplasmic surface area, and total cross-sectional surface area of capillaries. RESULTS: From stereologic morphometric studies, the serial changes in total cross-sectional surface area were not statistically significant (p = 0.152). However, there was a significant swelling of endothelial cytoplasm following ischemia and reperfusion (p = 0.0007). Meanwhile, changes in luminal surface area of capillaries following ischemia and reperfusion were also remarkable (p = 0.0008). CONCLUSIONS: The most striking finding of this study was the progressive decrease in capillary lumen during ischemia and after reperfusion. The swelling of endothelial cells is a major determinant of luminal narrowing of capillaries in patients receiving cardioplegic arrest.

Adolescent↗
PubMed2001

Embryonic expression patterns of the mouse and chick Gas1 genes.

Control of cell proliferation is essential to generate the defined form of a multi-cellular organism. While much is known about the regulators for cell cycle progression, relatively little is known about the state of growth arrest. Growth arrest (G0) is defined as a cell in a metabolically active but proliferation-quiescent state (reviewed in Baserga (1985) The Biology of Cell Reproduction), typically induced by serum starvation in vitro. Using subtractive hybridization, Schneider et al. (Cell 54 (1988) 787) identified six genes (Gas1 through Gas6) whose expressions are upregulated in serum-deprived NIH3T3 cells. Among the Gas genes, Gas1 is the only one that can cause growth arrest when expressed in cultured cell (Cell 70 (1995) 595; Int. J. Cancer 9 (1998) 569). Here, we describe for the first time the expression pattern of Gas1 during mouse embryogenesis. Our data reveal that Gas1 is expressed in many regions that the cells are actively proliferating and suggest that it may have other roles during development than negatively regulating cell proliferation. Furthermore, we have cloned the chick GAS1 gene and documented the similarity and divergence of Gas1 gene expression patterns between the two species.

Amino Acid Sequence↗
PubMed2001

Carbon-carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria.

In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha-N-substituted methyl pyrazole (10alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs <or=0.5-1 microg/mL and moderate Gram-negative activity with MICs=2-8 microg/mL against Haemophilus influenzae and Moraxella catarrhalis. This analogue was also found to have potent in vivo activity with an ED(50)=1.9 mg/kg. Beta-substitution at the C3-linked pyrazole generally results in a loss of activity. The C4-linked pyrazoles are slightly more potent than their counterparts in the C3-linked series. Most of the analogues in the C4-linked series exhibited similar levels of activity in vitro, but lower levels of activity in vivo than 10alpha. In addition, incorporation of a thioamide moiety in selected C4-linked pyrazole analogues results in an enhancement of in vitro activity leading to compounds several times more potent than eperezolid, linezolid and vancomycin. The thioamide of the N-cyanomethyl pyrazole analogue (34) exhibited an exceptional in vitro activity with MICs of <or= 0.06-0.25 microg/mL against Gram-positive pathogens and with MICs of 1 microg/mL against fastidious Gram-negative pathogens.

Anti-Bacterial Agents↗
PubMed2001

Characterization and immunological analysis of ferritin from the hemolymph of Galleria mellonella.

Ferritin, an iron-binding protein, was purified from the larval hemolymph of the wax moth, Galleria mellonella by KBr density ultracentrifugation and FPLC (Superose 6). The iron content of ferritin was determined by atomic emission spectroscopy and Ferene S stain. Native molecular mass of ferritin was estimated as 630 kDa. SDS-PAGE revealed that the ferritin consists of two major polypeptides of 26 and 32 kDa and one minor polypeptide of 30 kDa. An isoelectric point of ferritin was measured to be approximately 7.3 and only the 32-kDa subunit is glycosylated. The ferritin contains large amounts of lysine, glutamine, glutamic acid and leucine but tryptophan was not detected. Electron microscopic examination of negatively stained preparations showed an 11-nm particle in external diameter and 7-nm iron core. Ferritin is present in both the ovary and testis. Localization of ferritin by immunoelectron microscopy in ovary and testis revealed that the gold particles were located in vitelline membrane and yolk granules but not in follicular epithelium of ovary. In the testis, the gold particles were located in testicular fluid and lumen of vas deferens.

Amino Acids↗
PubMed2001

Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum.

Although the folate metabolic pathway in malaria parasites is a major chemotherapeutic target, resistance to currently available antifolate drugs is an increasing problem. This pathway, however, includes a number of enzymes that, to date, have not been characterized despite their potential for clinical exploitation. As a step towards evaluation of additional targets in this pathway, we report the isolation and characterization of 3 new genes that encode homologues of GTP cyclohydrolase I (GTP-CH), dihydrofolate synthase/folylpolyglutamate synthase (DHFS/FPGS) and serine hydroxymethyltransferase (SHMT). The genes encoding GTP-CH and SHMT are unambiguously assigned to chromosome 12, while that for DHFS/FPGS is tentatively assigned to chromosome 13. All 3 genes are expressed in blood-stage parasites, yielding transcripts of which only ca 60-70% is accounted for by coding sequence. All 3 of the proteins predicted to be encoded by these genes display sequence differences compared to the human host homologues that may be of functional significance. These data bring the complement of cloned genes that encode activities in the pathway to seven, leaving only the gene encoding dihydroneopterin aldolase (DHNA) to be identified in the route from GTP to folate synthesis and folate turnover in the thymidylate cycle.

Aldehyde-Lyases↗
PubMed2001

Protective effect of harmaline and harmalol against dopamine- and 6-hydroxydopamine-induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells.

The present study elucidated the protective effect of beta-carbolines (harmaline, harmalol and harmine) against oxidative damage of brain mitochondria, synaptosomes and PC12 cells induced by either dopamine or 6-hydroxydopamine. Harmaline, harmalol and antioxidant enzymes (superoxide dismutase/SOD and catalase) decreased the alteration of mitochondrial swelling and membrane potential induced by 200 microM dopamine or 100 microM 6-hydroxydopamine. Deprenyl attenuated the dopamine-induced mitochondrial dysfunction but did not reduce the effect of 6-hydroxydopamine. While beta-carbolines inhibited the electron flow in mitochondria, they did not enhance the depressant effect of catecholamines. beta-Carbolines and antioxidant enzymes reversed the depression of synaptosomal Ca2+ uptake induced by 10 microM catecholamines. The compounds inhibited the catecholamine-induced thioredoxin reductase inhibition, thiol oxidation and carbonyl formation in mitochondria and synaptosomes. beta-Carbolines decreased the reactive species-induced deoxyribose degradation. Harmaline and harmalol reduced the catecholamine-induced loss of the transmembrane potential and of cell viability in PC12 cells. beta-Carbolines alone did not show a significant cytotoxic effect on PC12 cells. The results suggest that beta-carbolines may attenuate the dopamine- or 6-hydroxydopamine-induced alteration of brain mitochondrial and synaptosomal functions, and viability loss in PC12 cells, by a scavenging action on reactive oxygen species and inhibition of thiol oxidation.

Animals↗
PubMed2001

Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: interleukin-17 expression is upregulated in early disease.

The aim of this study was to understand the immune processes controlling the initiation and spontaneous resolution of adjuvant arthritis (AA). We investigated synovial T-cell recruitment and mRNA expression of IL-17 and other important disease related cytokines, IFN-gamma, IL-2, IL-4, TNF and TGF-beta in inguinal lymph node (ILN) and synovial membrane (SM). Arthritis severity was assessed by a numerical rating score and rats were sacrificed every 3--4 days postadjuvant induction. Further assessment involved quantitative radiology and histology of the ankle joints on each day, and the ILN and SM were removed for RNA extraction. Cytokine mRNA expression was measured using RT-PCR and densitometry. Paraffin sections of rat ankle joints were stained for T-cells (CD3) by immunohistochemistry. In the ILN, there was an increase in IL-17, TNF and IFN-gamma expression in the early stages of disease, with a secondary sustained increase in IFN-gamma expression. In the SM, there was expression of T-cell cytokines in early arthritis (day 13), and prolonged TNF and TGF-beta expression, which reflected disease progression. IL-4 mRNA expression increased in the later stages of AA. Synovial T-cell numbers transiently increased at day 6, and remained high from days 13--28. Increased pro-inflammatory cytokine expression, including IL-17, in the ILN reflects the initiating events in the early stage of disease. IL-17 may therefore play an important role in the pathogenesis of AA. The increase in IL-4 (an anti-inflammatory cytokine) in the SM in the later stages of AA suggests that IL-4 is involved in the spontaneous resolution of AA. The initial increase in IFN-gamma in the ILN may reflect a pro-inflammatory response, while the prolonged secondary increase may indicate activation of regulatory T-cells.

Animals↗
PubMed2001

Bacillus subtilis mutations that alter the pathway of phosphorylation of the anti-anti-sigmaF factor SpoIIAA lead to a Spo- phenotype.

Sigma-F, the first sporulation-specific transcription factor of Bacillus subtilis, is regulated by an anti-sigma factor SpoIIAB, which can also act as a protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. The time course of phosphorylation reaction is biphasic, a fact that has been interpreted in terms of a mechanism for sequestering SpoIIAB away from sigmaF and thus allowing activation of sigmaF when needed. Site-directed mutagenesis of SpoIIAA has allowed us to isolate two mutants that cannot activate sigmaF and which are therefore Spo-. The two mutant SpoIIAA proteins, SpoIIAAL61A and SpoIIAAL90A, are phosphorylated with linear kinetics; in addition they are less able to form the stable non-covalent complex that wild-type SpoIIAA makes with SpoIIAB in the presence of ADP. The phosphorylated form of SpoIIAAL90A was hydrolysed by the specific phosphatase SpoIIE at the same rate as wild-type SpoIIAA-P, but the rate of hydrolysis of SpoIIAAL61A-P was much slower. The secondary structure and the global fold of the mutant proteins were unchanged from the wild type. The results are interpreted in terms of a model for the wild type in which SpoIIAB, after phosphorylating SpoIIAA, is released in a form that is tightly bound to ADP and which then makes a ternary complex with an unreacted SpoIIAA. We propose that it is the inability to make this ternary complex that deprives the mutant cells of a means of keeping SpoIIAB from inhibiting sigmaF.

Adenosine Diphosphate↗
PubMed2001

Shift of the gastric T-cell response in gastric carcinoma.

BACKGROUND AND AIMS: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. RESULTS: Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. CONCLUSIONS: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.

Adenocarcinoma↗
PubMed2001

nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver.

AIMS: The nm23 gene has been shown to have metastasis suppressing activity and abnormalities of the gene or its expression may be important in tumour progression and dissemination. This study was set out to investigate the possible role of the nm23 in colorectal adenocarcinoma dissemination by examining the level of nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. METHODS: Using a monoclonal antibody, NCL-nm23 (Novocastra), immunohistochemical expression of the nm23 protein was examined in cases of metastatic colorectal adenocarcinoma in regional lymph nodes (n=71) and liver (n=36). RESULTS: The cases of lymph-node metastasis also had tissues from the primary carcinoma (n=71) and matching normal non-neoplastic mucosal tissues (n=71) from the colon and rectum available for the study. More than half of the cases of primary colorectal carcinoma (43/71; 60%) displayed strong nm23 immunoreactivity, with a similar proportion of the lymph-node metastases (40/71 cases; 56%) having strong nm23 immunostaining. However, only a small minority of the normal controls of non-neoplastic colorectal epithelia (12/71 cases; 17%) had strong nm23 immunoreactivity. The difference in nm23 protein expression between normal colorectal mucosa and primary colorectal carcinoma was statistically significant (P=0.0001; chi-squared test with continuity correction). However, no significant difference in nm23 protein expression was found between primary colorectal carcinoma and lymph-node metastases (P=0.81; chi-squared test with continuity correction). Most of the liver metastases (24/36 cases; 67%) had strong nm23 immunostaining but this finding was not statistically significant when compared with that seen in primary colorectal carcinoma (P=0.62; chi-squared test with continuity correction). In addition, nm23 expression was not found to significantly correlate with 5-year survival of patients with liver metastasis (P=0.86), suggesting that it had no predictive value for overall patient survival. There was also no significant correlation between disease recurrence and nm23 expression (P=0.63). CONCLUSIONS: In summary, increased nm23 protein immunoreactivity is seen in the majority of colorectal carcinomas when compared to normal colorectal tissues but no significant difference in nm23 expression was found between primary colorectal carcinoma and metastatic carcinoma in regional lymph nodes or the liver. This study suggests that increased nm23 expression may be important in early colorectal carcinoma but not in later progression and dissemination of the tumour. In conclusion, the role and importance of the nm23 gene in the development of tumour metastasis in colorectal carcinoma is questionable.

Biomarkers, Tumor↗
PubMed2001

Mucinous differentiation in colonic adenocarcinoma is associated with a reduction in tumour-infiltrating lymphocytes.

AIMS: The aim of this study was to examine the density of tumour-infiltrating lymphocytes (TILs) in colorectal carcinomas showing mucinous differentiation. METHODS: We examined 33 adenocarcinomas showing variable mucinous differentiation and compared the density of TILs with that of 65 adenocarcinomas of no special type (NOS) showing no mucinous differentiation. RESULTS: Mucinous differentiation is associated with a significantly lower density of TILs compared to adenocarcinoma NOS (P=0.0016; chi-squared test with continuity correction). This reduction in TILs is present also in adjacent foci of adenocarcinoma NOS within mucinous tumours. CONCLUSIONS: There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show mucinous differentiation, which may help explain the increased biological aggressiveness associated with this pattern of differentiation.

Adenocarcinoma↗
PubMed2001

Editorial: the changing face of pathology.

As the journal advances into its 33rd volume of publication and into the new millennium, significant developments in information technology have allowed restructuring of the format, review and publishing procedures of the journal, Pathology. This in turn enables rapid publication of timely and significant articles of interest to both diagnostic and research pathologists. There is an emphasis to develop the educational and professional development aspects of the journal while maintaining a rigorous peer review process to ensure publication of high quality research and review articles. A number of changes that will facilitate these processes are outlined. The journal is also available on-line on the web in PDF format and there are considerations made to further exploit this avenue of communication for the publication of supplementary material. The Editor and Editorial Board encourages Fellows of the Royal College of Pathologists, readers and authors to communicate their views on these and other future developments with the Editorial Office.

Internet↗
PubMed2001

The emerging role of the human herpesvirus 8 (HHV8) in human neoplasia.

The human herpesvirus 8 (HHV8) was initially described and characterised in Kaposi's sarcoma tissue. The virus was found in the lesion of most cases of Kaposi's sarcoma. Whilst there is a large body of evidence to implicate its role in the pathogenesis of Kaposi's sarcoma, it has recently been found that the virus may also be important in a number of other human neoplasias. This review will examine the molecular pathology of HHV8 in the pathogenesis of Kaposi's sarcoma and summarise the current evidence and postulated mechanisms in its role in other human neoplasias.

AIDS-Related Opportunistic Infections↗
PubMed2001

Can phyllodes tumours of the breast be distinguished from fibroadenomas using fine needle aspiration cytology?

In an attempt to determine whether it is possible to distinguish phyllodes tumours (PTs) of the breast from fibroadenomas (FAs) using fine needle aspiration cytology (FNAC), we reviewed the cytological slides of eight histopathologically confirmed PTs (six benign and two malignant) and compared them with cytological features of 13 histopathologically confirmed FAs. Each author independently, "blindly" assessed architectural and cytological features of the stromal (six features) and epithelial (seven features) components and the cytological background (three features) and gave a favoured diagnosis for each case. Four of six benign PTs, one of two malignant PTs and 11 of 13 FAs were correctly diagnosed cytopathologically by at least three of the authors. The presence of hypercellular stromal fragments was the most useful feature in distinguishing PTs from FAs, and the presence of cytological atypia of the stromal cells was the most important feature in distinguishing malignant from benign PTs. Sampling error was the most common reason for cytological misdiagnosis of PTs. The two FAs misdiagnosed as PTs were each of cellular type. The results of this study suggest that it is possible to distinguish PTs from FAs using FNAC in most cases. We recommend that if hypercellular stromal fragments are identified in a FNAC specimen of a fibroepithelial lesion, the cytopathologist should raise the possibility of a PT and the surgeon treat the patient accordingly.

Biopsy, Needle↗
PubMed2001

Crosslinking of alpha 2-antiplasmin to fibrin.

Human alpha 2-antiplasmin (alpha 2AP) is the primary inhibitor of plasmin-mediated fibrinolysis and is an efficient substrate of activated factor XIII (FXIIIa). Among 452 amino acid residues in alpha 2AP, Gln2 is believed to be the sole FXIIIa-reactive site that participates in crosslinking alpha 2AP to fibrin. We studied the effect of mutating Gln2 on the ability of FXIIIa to catalyze crosslinking of alpha 2AP to fibrin. By FXIIIa catalysis, [14C]methylamine was incorporated into a Q2A-alpha 2AP mutant in which Gln2 (Q) was replaced by Ala (A), thereby indicating that wildtype alpha 2AP has more than one FXIIIa-reactive site. To identify the FXIIIa-reactive sites in alpha 2AP, wildtype alpha 2AP and Q2A-alpha 2AP were labeled with 5-(biotinamido)pentylamine by FXIIIa. Each labeled alpha 2AP was digested with trypsin and applied to an avidin affinity column to capture labeled peptides. Edman sequencing and mass analysis of each labeled peptide showed that out of 35 Gln residues in wildtype alpha 2AP, four were labeled with the following order of efficiency: Gln2 > Gln21 > Gln419 > Gln447. Q2A-alpha 2AP was also labeled at the three minor sites, Gln21 > Gln419 > Gln447. Q2A-alpha 2AP became crosslinked to fibirin(ogen) by FXIIIa catalysis at approximately one-tenth the rate of wt-alpha 2AP. These results demonstrate that alpha 2AP has one primary (Gln2) and three minor substrate sites for FXIIIa and that the three minor sites identified in this study can also participate in crosslink formation between alpha 2AP and fibrin, but at a much lower efficiency than the Gln2 site.

Fibrin↗
PubMed2001

Comparative T-cell responses during pregnancy in large animals and humans.

PROBLEM: Placentation in different large animal species shows a remarkable diversity in the level of trophoblast invasion into the maternal endometrial tissues. We wish to determine the influence of implantation on T-cell responses during pregnancy. METHOD OF STUDY: Review of the literature and current data. RESULTS: alphabeta-TCR+ T cells are only prominent during early pregnancy in species with relatively non-invasive placentation (pig and horse) but are rapidly downregulated in species with more invasive placentae. gammadelta-TCR+ T cells are prominent in species with moderate trophoblast invasion (ruminants) where they increase dramatically during mid and late pregnancy. gammadelta-TCR+ T cells remain prominent during late gestation in species with highly invasive placentation (humans) and, in addition, a distinct gammadelta T-cell population is present in first trimester decidua where it may play a regulatory role in controlling natural killer cell activity. The gammadelta-TCR+ population present in both ruminants and humans shows large granular morphology and contains antimicrobial proteins, suggesting their function may be to protect the uterine environment from infection during pregnancy and parturition. CONCLUSION: The comparative analysis of T-cell responses during pregnancy in different large animal species supports an increasing role for cells of the innate immune response (NK and gammadelta T cells) and a downregulation of the adaptive immune response with increasingly invasive placentation.

Animals↗