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Biomedical subjects

C M Schmidt

Publications and source records attributed to C M Schmidt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Preoperative terminal ileal and colonic resection histopathology predicts risk of pouchitis in patients after ileoanal pull-through procedure.

OBJECTIVE: This study seeks to compare the histopathology of preoperative terminal ileal and colonic resection specimens with pouch biopsies after the ileoanal pull-through (IAPT) procedure. SUMMARY BACKGROUND DATA: Pouchitis is the most frequent complication of transanal continent reservoirs in patients after IAPT. METHODS: The authors conducted 751 consecutive pouch biopsies on 73 patients with inflammatory bowel disease or familial adenomatous polyposis who underwent IAPT by a single surgeon over a 10-year period. In this preliminary report, a pathologist, in blinded fashion, has graded 468 of the IAPT pouch biopsies and 67 of the patients' preoperative terminal ileal and colonic resection histopathology to date. Colonic histopathology was graded by the extent and severity of disease, terminal ileal and pouch histopathology by active inflammation, chronic inflammation, lymphocyte aggregates, intraepithelial lymphocytes, eosinophils, and villous blunting. RESULTS: Extent of colonic disease (gross and microscopic) was a significant predictor of active inflammation in subsequent IAPT pouch biopsy specimens. Also, the gross extent of colonic disease exhibited a significant linear association with pouch inflammation. However, the severity of colonic disease was not significantly predictive of active inflammation in subsequent IAPT pouch biopsies. Terminal ileal active and chronic inflammation were significant predictors of subsequent IAPT pouch inflammation. Although lymphocyte aggregates and intraepithelial lymphocytes were not predictive, terminal ileum eosinophils and villous blunting were significant predictors of active inflammation in subsequent IAPT pouch biopsy specimens. CONCLUSIONS: Preoperative terminal ileal and colonic histopathology predicts active inflammation of pouches after IAPT. Patients who are preoperatively assessed to have extensive disease of the colon, ileal disease ("backwash ileitis"), or both appear to be at greater risk for the development of pouchitis after IAPT.

Adenomatous Polyposis Coli↗
PubMed1998

A study of antibody and T cell recognition of rhoptry-associated protein-1 (RAP-1) and RAP-2 recombinant proteins and peptides of Plasmodium falciparum in migrants and residents of the state of Rondonia, Brazil.

Humoral and cellular responses were examined among natives and migrants in an area of the Amazon region of Brazil. Rhoptry-associated protein-1 (RAP-1) and RAP-2 expressed in Escherichia coli expression systems, a peptide corresponding to the epitope bound by inhibitory anti-RAP-1 antibodies, and four other RAP-1 and RAP-2 synthetic peptides were used in these studies. Plasma from the native population had greater IgG reactivity to the N-terminal third of RAP-1 than the migrant population; both populations had low levels of IgM to this region of RAP-1. The IgG reactivity to RAP-2 and to the C-terminal third of RAP-1, as well as for all the peptides, including the peptide from the inhibitory domain, were low or absent in both populations. In contrast, there were a high number of subjects with an IgM response to the peptides. Cellular responses were measured by proliferation of peripheral blood mononuclear cells (PBMC) and, in some subjects, by reverse transcription-polymerase chain reaction for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, and IL-10. Proliferation of PBMC was low when stimulated by recombinant proteins, peptides, or parasite lysate. Both RAP-1 and RAP-2 stimulated cytokine production by donor T cells; IL-2, IL-4, and IFN-gamma RNA transcripts were observed in response to recombinant proteins and parasite lysate, but with no uniform trends. From the observed antibody responses, RAP-1 appears to be more immunogenic than RAP-2.

Adolescent↗
PubMed1997

Increased MAPK expression and activity in primary human hepatocellular carcinoma.

We investigated the expression and activity of mitogen-activated protein kinase (MAPK) in human hepatocellular carcinoma (HCC). MAPK expression was determined in five human tumors and five normal tissues (adjacent non-neoplastic liver) by Western blotting using specific antisera raised against four MAPK pathway intermediates: Erk-1, Erk-2 (extracellular-signal regulated kinases), Mek-1 and Mek-2 (mitogen activated protein kinase kinases). There was a significant increase in Erk-1, Erk-2, Mek-1 and Mek-2 expression in particulate and cytosolic fractions prepared from tumor specimens as compared with the adjacent normal control tissues. The functional activity of both membrane and cytosolic Erk-2, determined by phosphorylation of myelin basic protein (MBP), was significantly increased in tumor specimens as compared to normal (membrane: 321%+/-50%, p<0.05; and cytosol: 597%+/-233%, p<0.05 percent of normal tissue). These data demonstrate for the first time a significant increase in MAPK expression and functional activity in human HCC. Because of the important role that the MAPK pathway plays in cellular growth and differentiation, overexpression of MAPK may be of critical importance to the formation and maintenance of human hepatocellular carcinoma.

Blotting, Western↗
PubMed1997

Alterations in guanine nucleotide regulatory protein expression and activity in human hepatocellular carcinoma.

Alterations in the expression and activity of guanine nucleotide regulatory proteins (G proteins) have been linked to the growth of several human tumors. We hypothesized that the expression and activity of G proteins are altered in human hepatocellular carcinoma (HCC). The expression of Gi and Gs proteins was determined in six human tumors and six normal controls (adjacent nonneoplastic liver) by Western blotting using specific antisera raised against the alpha subunit of G proteins Gi1, Gi1-2, Gi3, and Gs. Differences in G-protein expression were quantified by densitometry and expressed as percentage change from normal controls. The expression of Gi alpha1 was significantly increased in 80% of tumors (Gi alpha1, 284% +/- 77%; P < .05 percent of normal tissue), whereas Gi alpha1-2 and Gi alpha3 expression was increased in 67% of tumors (Gi alpha1-2, 218% +/- 21%; Gi alpha3, 154% +/- 6%; P < .05 percent of normal tissue). The functional activity of Gi alpha proteins as determined by pertussis toxin-catalyzed adenosine diphosphate (ADP)-ribosylation was also significantly increased in these tumors. In contrast, Gs alpha-protein expression was significantly reduced in all tumors examined (74% +/- 8% of normal tissue, P < .05). The functional activity of Gs alpha, as determined by adenylyl cyclase (AC) activity, was significantly decreased in tumor as compared to normal liver under both basal and agonist stimulated (guanosine triphosphate gamma S and forskolin) conditions. In summary, these data show for the first time a significant alteration in G-protein expression and functional activity in human HCC tissue. These alterations indicate a down-regulation of the AC-linked enzyme effector system in HCC that may be of critical importance to the formation and progression of human hepatocellular carcinoma.

Adenosine Diphosphate Ribose↗
PubMed1997

Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma.

The mitogen-activated protein kinase (MAPK) cascade acts as a focal point for signal transduction following activation of both G-protein-linked and tyrosine kinase growth factor receptors. A common intermediate between both of these diverse receptor subtypes includes the small guanosine triphosphate (GTP)-binding protein, p21ras. Point mutations of p21ras have been identified in various tumor types and lead to constitutive activation of this protein and subsequent activation of downstream pathways including the MAPK cascade. Using an in vivo model of hepatocellular carcinoma (HCC), we investigated the abundance and function of individual components of the MAPK cascade and the presence of specific p21ras mutations in this model. Expression of components of the MAPK cascade were determined in tumor and adjacent, non-neoplastic liver specimens by Western blot analysis and functional activity confirmed by substrate phosphorylation assays. Mutations in p21ras were analyzed using an enzyme-linked immunosorbent assay. In tumor, extracellular regulated kinases (ERKs) ERK1, ERK2, and mitogen-activated ERK-regulated kinase-1 (MEK1) were elevated by three- to fourfold as compared with adjacent nontumorigenic normal liver. In contrast, MEK2 was elevated by only 28%. Substrate phosphorylation and detection of phosphorylated ERK1/2 proteins showed increased functional activity of these proteins of the same magnitude as that observed for protein expression. Mutations in p21ras were not detected in this experimental model of HCC. We conclude that HCC is associated with marked changes in expression and function of components of the MAPK cascade independent of common p21ras mutations.

Animals↗
PubMed1997

Cytotoxic T lymphocyte recognition of HLA-G in mice.

Several features of HLA-G's sequence and expression pattern distinguish HLA-G from its classical counterparts. These features, including HLA-G's limited polymorphism and its expression at the maternal-fetal interface, have been used as a basis for suggesting a distinct functional role for this nonclassical class I HLA molecule. On the other hand, published data do demonstrate that HLA-G has much in common with its classical counterparts. It associates with beta 2-microglobulin and cytosolic peptides, it binds to CD8, and its presence can inhibit NK-cell-mediated lysis of HLA-G-bearing target cells. To develop a model in which HLA-G's function could be more thoroughly studied, we produced several HLA-G-expressing transgenic mouse strains. We report here the results of skin graft experiments which show that nontransgenic mice reject HLA-G-expressing transgenic murine skin as foreign and that this rejection is associated with the presence in the recipient of lymphocytes capable of specifically lysing HLA-G-expressing cells. In addition, experiments are described which demonstrate that HLA-G transgenic mice recognize HLA-G as a "self" molecule. Together the reported data demonstrate that HLA-G is capable of stimulating an HLA-G-restricted CTL response, that HLA-G molecules can serve as target molecules in lytic interactions with CTLs, and that HLA-G is involved in education of the lymphocytic repertoire of HLA-G transgenic mice.

Adult↗
PubMed1997

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation.

PURPOSE: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. SETTING: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. METHODS: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. RESULTS: Mean follow-up was 16.7 months +/- 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperatively, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). CONCLUSION: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Aged↗
PubMed1997

A color Doppler analysis of nifedipine-induced posterior ocular blood flow changes in open-angle glaucoma.

PURPOSE: This pilot study used color Doppler imaging to investigate the effects of nifedipine on the posterior ocular blood flow of patients with glaucoma progression at normal intraocular pressures. PATIENTS AND METHODS: Eighteen patients, 11 men and seven women with a median age of 61.7 years, were imaged before and 6 weeks after the initiation of 30 mg of sustained-release nifedipine (Procardia XL; produced by either Pfizer or Pratt) daily. RESULTS: There was no statistically significant change in the blood velocity of the ophthalmic artery, central retinal artery, and main nasal and temporal short posterior ciliary arteries after treatment with nifedipine. CONCLUSION: The routine use of nifedipine in patients with normal tension glaucoma progression is not supported by this study.

Adult↗
PubMed1997

Encapsulated filtering blebs after trabeculectomy with mitomycin-C.

BACKGROUND AND OBJECTIVE: To determine the frequency of encapsulated blebs after guarded filtration procedures with mitomycin-C. PATIENTS AND METHODS: The authors reviewed the charts of all patients who had undergone a guarded filtration procedure with mitomycin-C. There were 235 patients (283 cases) who had more than 1 month of follow-up. RESULTS: An encapsulated bleb developed in 7 eyes (2.47%) of 6 patients. Identification of bleb encapsulation occurred at a mean follow-up time of 29.7 +/- 14.6 days after surgery. The mean intraocular pressure at that point was 24.2 +/- 13.5 mm Hg in the affected eyes. Three eyes were treated medically, and needling was performed in 4 eyes. CONCLUSION: There is a low frequency of encapsulated bleb formation after guarded filtration procedures with adjunctive mitomycin-C.

Administration, Topical↗
PubMed1997

Simultaneous use of mitomycin-C with Baerveldt implantation.

BACKGROUND AND OBJECTIVE: To evaluate the outcome of Baerveldt implantation with adjunctive mitomycin-C in cases of complicated glaucoma. PATIENTS AND METHODS: The authors reviewed the charts of all patients who had undergone Baerveldt implantation with mitomycin-C between January 1993 and March 1995. Success was defined before data collection as an intraocular pressure (IOP) between 5 and 21 mm Hg, with or without medications. The success rate was calculated using the Kaplan-Meier actuarial method. RESULTS: Twenty-nine patients were identified. The mean preoperative IOP was 33.6 mm Hg, with an average of 2.0 antiglaucoma medications. The probability of success at 6 and 12 months for patients who received mitomycin-C during Baerveldt implantation was 82.4% and 73.3%, respectively. Choroidal effusion with a flat anterior chamber (10.3%), corneal edema (6.8%), and conjunctival erosion (6.8%) were the most frequent complications. CONCLUSION: In this retrospective series of complicated glaucoma, the implantation of a Baerveldt drainage device with adjunctive mitomycin-C had a satisfactory outcome. The complications encountered and the clinical efficacy were comparable to those of previously reported series in which mitomycin-C was not used.

Antibiotics, Antineoplastic↗
PubMed1996

Simple radiographic evaluation of ileoanal pouch volume.

PURPOSE: Total colectomy and mucosal protectomy with ileal reservoir and anal pull-through is used in the treatment of ulcerative colitis or familial polyposis, with one complication being frequent bowel movements. A simple radiographic test to predict frequency of bowel movements and measure spasticity was evaluated. METHODS: Fourteen patients underwent evaluation after ileal reservoir and anal pull-through J-pouch construction. Barium sulfate suspension was instilled into the pouch via the anus in the standing position until reflux flowed into the small intestine proximal to the pouch and patients felt the urge to defecate. Total volume infused (VOLtot), volume to reflux (VOLrflx), and volume voided (VOLvoid) were measured. RESULTS: VOLvoid and the "voiding efficiency" (VOLvoid/VOLtot) correlated significantly with stool frequency (R=-0.744, P<0.002 and R=-0.754, P<0.002, respectively). Time from operation was correlated with VOLvoid and stool frequency (R=-0.723, P<0.003 and RO.573, P<0.032, respectively). CONCLUSIONS: The addition of quantitative measurements to this radiographic test gives useful information about pouch performance. Furthermore, the data imply that spasticity, as measured by voiding quantum and efficiency, rather than actual pouch volume is a major determinant of bowel movement frequency.

Adult↗
PubMed1996

Formula revealed.

Explore the source record for details and available documents.

Antibiotics, Antineoplastic↗
PubMed1996

Clinical implications of the white nipple sign and its role in the diagnosis of esophageal variceal hemorrhage.

OBJECTIVE: Differentiation of esophageal variceal hemorrhage from other sources of the GI tract is often difficult. This is a prospective investigation of the significance of the white nipple sign in patients with recent esophageal variceal hemorrhage. METHODS: One hundred sixty-six patients with recent variceal hemorrhage were prospectively studied with respect to presence or absence of the white nipple sign and other stigmata of hemorrhage and compared with 100 patients with known varices but without a clinical history of bleeding. RESULTS: The white nipple sign correlated positively with severity of bleeding (patients required more blood transfusion), hematemesis, and signs of shock. Patients with the white nipple sign also tended to undergo emergency endoscopy and have active bleeding at the time of endoscopy. There was no correlation between rebleeding rate after endoscopic therapy and presence of the white nipple sign. Appearance of the white nipple sign was closely related to the timing of endoscopy (p < 0.0001). The sensitivity and specificity of the white nipple sign in the diagnosis of esophageal variceal hemorrhage were 21 and 100%, respectively, compared with 100 and 54% for the red color sign. Furthermore, the sensitivity of the white nipple sign increased with shorter times between bleeding and endoscopy. CONCLUSIONS: In patients with upper GI bleeding, the white nipple sign suggests that the varices bled recently and that the bleeding was severe. However, it has no predictive value for rebleeding after endoscopic therapy. Earlier endoscopy (i.e., within 24 h of bleeding) is suggested to improve the diagnostic rate of esophageal variceal hemorrhage.

Case-Control Studies↗
PubMed1995

Temporal and spatial expression of HLA-G messenger RNA in extraembryonic tissues of transgenic mice.

HLA-G, a nonclassical class I molecule, is expressed by trophoblasts, the only fetal cells in direct contact with maternal tissue. Results of previous experiments suggested that a 244-bp region located over 1 kb 5' from exon 1 is critical for extraembryonic expression of HLA-G in transgenic mice. We report here the production of HLA-G transgenic lines with a 6.0-kb HLA-G transgene that includes the 244-bp region. These lines exhibit copy number-dependent and developmentally appropriate transgene expression. One HLA-G transgenic line, G.3.2, exhibits extraembryonic HLA-G mRNA expression levels similar to those seen in human extraembryonic tissues. Studies of the cell-type-specific localization of HLA-G mRNA in placentas from the G.3.2 HLA-G transgenic mouse line show predominant localization of the HLA-G message in the spongiotrophoblast layer. This layer is in a similar anatomic location to the HLA-G-expressing human cytotrophoblast shell. The G.3.2 HLA-G transgenic mouse line should serve as an appropriate model for the study of HLA-G function at the maternal-fetal interface.

Animals↗
PubMed1995

Management of overfiltering and leaking blebs with autologous blood injection.

We describe our experience with intrableb autologous blood injection to manage over-filtering and leaking blebs. Autologous blood was injected into 12 thin cystic filtration blebs of 12 eyes. Indications for blood injection included symptomatic hypotony in five eyes, hypotony associated with bleb leakage in five eyes, and bleb leakage without hypotony in two eyes. Seven eyes (58.3%) were classified as successes and five eyes (41.7%) were classified as failures. The mean (+/- SD) follow-up was 6.8 +/- 2.6 months. Among the eyes classified as successes, a significant increase was noted in intraocular pressure and visual acuity by a mean (+/- SD) of 5.1 +/- 2.9 mm Hg and 5.3 +/- 2.1 lines, respectively. Bleb leakage resolved in four of seven eyes. The most common complication was hyphema formation. Injection of autologous blood into a filtration bleb is an alternative procedure for management of excessive filtration or bleb leakage in selected patients.

Adult↗
PubMed1995

The secretary pathway of plasmodium falciparum regulates transport of p82/RAP1 to the rhoptries.

The rhoptries of Plasmodium falciparum are formed during a restricted period in the asexual erythrocytic cycle. The steps required for rhoptry biogenesis and the pathway for targeting proteins to the rhoptries have not been elucidated. Using the maturation of the Rhoptry-Associated Protein 1 (RAP-1) gene product to study these steps, it is reported here that a secretory pathway controls transport of protein complexes containing RAP-1 products to the rhoptries. Both brefeldin A (BFA) and low temperature reversibly block the processing of an 86-kDa precursor (Pr86) to the mature 82-kDa RAP-1 product (p82). Furthermore, the points of action of BFA and low temperature appear to overlap since their sequential application reversibly prevents Pr86 processing. Treatment of intact cells with N-ethylmaleimide, which prevents the fusion of transport vesicles with Golgi membranes in other eukaryotic cells, irreversibly blocks processing of Pr86. The role of the secretory pathway in targeting p82 protein complexes to the rhoptries product of RAP-1. These in vitro results also reveal that the RAP-1 product contains a cleavable N-terminal signal peptide and appears to be initially synthesized as an 84-kDa protein. The above data indicate that transport of p82 to the rhoptries is regulated by the secretory pathway and that the RAP-1 primary translation product differs in apparent molecular weight from the in vivo precursor Pr86. Our results suggest that rhoptry biogenesis is controlled in part by the secretory pathway and that the RAP-1 gene product acquires a previously undetected protein modification during its maturation.

Animals↗
PubMed1995

HLA-G transgenic mice: a model for studying expression and function at the maternal/fetal interface.

Experiments designed to identify all HLA class I genes led to the cloning of the HLA-G gene (Geraghty et al. 1987). Very low levels of HLA-G mRNA expression have been demonstrated in the eye, thymus, peripheral blood lymphocytes and in keratinocytes (Shukla et al. 1990, Ishitani & Geraghty 1992, Kirszenbaum et al. 1994, Ulbrecht et al. 1994). Higher levels of HLA-G expression were demonstrated in certain subpopulations of trophoblasts (Ellis et al. 1990, Kovats et al. 1990). Specifically, those subpopulations of trophoblasts in direct contact with decidua, i.e. the cytotrophoblasts of the cytotrophoblast shell and columns, invasive cytotrophoblasts, and cytotrophoblasts of the chorionic membrane, express HLA-G (Yelavarthi et al. 1991, Chumbley et al. 1993). HLA-G molecules on these cells are in a position to interact directly with the maternal immune system. HLA-G transgenic mice have been produced in an effort to produce a model in which antigen presentation by HLA-G can be studied. Studies utilizing these transgenic mice have led to the definition of a previously unknown regulatory region and have yielded some basic information about HLA-G's ability to function as a class I molecule (Schmidt et al., in press; manuscript in preparation). One of the HLA-G transgenic mouse lines produced, G.3.2, has been shown to have a cell-type specific extraembryonic HLA-G expression pattern paralleling that seen in human extraembryonic tissues (Schmidt et al, in press). In addition, the levels of HLA-G mRNA expression seen in the extraembryonic tissues from this transgenic mouse line are similar to the levels of HLA-G mRNA expression detectable in human extraembryonic tissues. As cells expressing HLA-G come in direct contact with decidual cells, these mice will serve as a model in which HLA-G's ability to present foreign antigens to the maternal immune system can be studied. The G.3.2 HLA-G transgenic mouse line also exhibits thymic HLA-G expression levels similar to those seen in human thymus (Schmidt et al., manuscript in preparation). HLA-G expression in the transgenic murine thymus is largely restricted to dendritic cells. It is possible that this thymic HLA-G mRNA expression is responsible for the tolerance to HLA-G which is seen in the HLA-G transgenic mice. Further studies will be necessary to determine whether the lymphocytic repertoire of the HLA-G transgenic mouse can recognize HLA-G molecules presenting foreign peptides.

Animals↗