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Biomedical subjects

D Chapman

Publications and source records attributed to D Chapman.

At least 127 records · Page 7Linked to original sources
PubMed1990

Metastatic adenocarcinomas of unknown primary site. Prognostic variables and treatment results.

As part of a Phase II chemotherapy trial using mitomycin-C, adriamycin, and vindesine, 57 patients with adenocarcinoma of unknown primary site were assessed for prognostic variables predictive of response and survival. They were also evaluated for response and toxicity, usefulness of screening techniques, and eventual definition of primary site and pattern of progression. Only gender predicted response, with women being more likely to respond than men. Visceral metastases below the diaphragm, or the presence of liver metastases, predicted poor survival. Responding patients were highly likely to relapse first at sites of initial disease. Hemolytic-uremic syndrome was the most severe toxicity; other side effects were moderate. The response rate was 30% (three complete responders), which is similar to other current regimens. This study suggests that patients with better prognosis characteristics of single site of disease and without intraabdominal tumor may benefit from a policy of expectant observation after local control has been established. Patients with multiple sites of disease and/or intraabdominal tumor are appropriate candidates for investigational chemotherapy.

Adenocarcinoma↗
PubMed1990

A stereotactic technique for volumetric interstitial implantation in the brain.

Stereotaxis, a method of localizing a specific point using three dimensional coordinates, has greatly improved since the advent of computed tomography (CT). A simple, noninvasive stereotactic system which enables rapid, parallel placement of multiple interstitial catheters for treatment of malignant brain tumors has been developed. Departing from traditional stereotactic methods, the implantation procedure is performed in one stage--entirely in the CT suite. Perioperative nursing responsibilities include mastering the technical aspect of a high precision system as well as meeting the special needs of the patient undergoing this procedure. Initially developed for use in volumetric interstitial brachytherapy, the procedure is now being used in Phase II clinical trials of volumetric interstitial hyperthermia in the management of patients with intracranial malignancies.

Brachytherapy↗
PubMed1990

Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium.

Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer.

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.

Adult↗
PubMed1990

Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin's disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy.

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

Adult↗
PubMed1990

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.

Analysis of Variance↗
PubMed1990

[Intraportal injection of specific monoclonal antibody in nude mice with liver metastasis].

To assess the importance of monoclonal antibody route of administration, we compared the selective (intraportal) and systemic injection of specific radiolabeled monoclonal antibody, using a murine model of hepatic metastases from a human colorectal carcinoma. Tumor uptake was studied over time after injection of 0.1, 1.0 or 2.0 micrograms of a specific antibody (HT29-15) or an isotype-matched control (BL-3). Significantly higher tumor uptake and tumor/liver or tumor/blood uptake ratios were seen in animals receiving intraportal injection for all tested doses. Intraportal injection of specific monoclonal antibody resulted in significant improvement in metastases uptake; these findings could be applied to the diagnosis and treatment of hepatic metastases from colorectal cancer using radiolabeled monoclonal antibodies.

Adenocarcinoma↗
PubMed1990

Histology of early lesions of AIDS-associated Kaposi's sarcoma.

The original cutaneous biopsy specimens of 93 patients who presented themselves to the Memorial Sloan-Kettering Cancer Center with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were systematically reviewed for 23 histologic variables. KS was the initial manifestation of AIDS in all of the patients. The vast majority of patients presented with plaque histology of KS. Early lesions of KS were characterized by the presence of dilated vascular spaces haphazardly arranged in the biopsy specimen, a sparse inflammatory cell infiltrate composed of lymphocytes (usually without plasma cells), and aggregates of cuboidal cells with the appearance of epithelioid cells. Individually necrotic tumor cells were present in nearly every case. Spindle cells arranged in fascicles or nodules were seen in a minority of cases. These data provide an overview of the different histologic patterns seen in initial lesions of AIDS-associated KS and may lead to better understanding of the pathogenesis of this tumor.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Intrahepatic mitomycin C as a salvage treatment for patients with hepatic metastases from colorectal carcinoma.

Sixty-four evaluable patients with hepatic metastases from colorectal carcinoma, who did not have evidence of extrahepatic disease, were treated with intrahepatic (IH) mitomycin C (M) after disease progression or intolerance to treatment with IH fluorodeoxyuridine (FUDR). Eleven patients (17%) had a partial response (PR) to IH M and ten (16%) patients had stable disease. Patients who responded to IH FUDR were more likely to respond to IH M when compared with those who progressed on IH FUDR (47% versus 13%, respectively; P = 0.013). Those who were switched to IH M because of hepatotoxicity on IH FUDR also were more likely to respond to IH M than those who were switched because of progression on IH FUDR (75% versus 27%, respectively; P = 0.022). Baseline laboratory values, the percent of tumorous liver involvement, prior history of systemic chemotherapy, and the interval from diagnosis to initiation of IH M did not help predict response. Toxicity was mild and well tolerated. The overall median survival time of the 64 evaluable patients was 9.0 months from the start of IH M therapy. We conclude that IH M has some salvage benefit in patients with hepatic metastases.

Colorectal Neoplasms↗
PubMed1989

The binding of phosphorylcholine-carrying antigens to the anti-phosphorylcholine monoclonal antibody TEPC 15. A fluorescence spectroscopic study.

The intrinsic fluorescence of the anti-phosphorylcholine monoclonal antibody TEPC 15 has been used to study its interaction with the hapten phosphorylcholine and some phosphorylcholine-carrying lipids. Spectral conditions were selected so as to obtain fluorescence emission attributable mainly to tryptophan residues. Upon addition of the hapten, the fluorescence intensity increases, and the emission maximum is shifted towards lower wavelengths, in a hyperbolic and saturable process. These effects seem to be specific for phosphorylcholine, since they are not produced by the analogue phosphorylethanolamine. The quenching results suggest that a conformational change occurs in the protein upon interaction with the hapten. Upon addition of a variety of phosphorylcholine-carrying lipids, it is shown that the antibody interacts with the hapten when the lipid exists in the form of micelles, but not when it is present in the lamellar phase.

Animals↗
PubMed1989

Secondary structure in properdin of the complement cascade and related proteins: a study by Fourier transform infrared spectroscopy.

Six structural repeat motifs of 58 amino acids are found in the sequence of both mouse and human properdins. Twelve more examples of the motif are available from the sequences of thrombospondin, the terminal complement components, and the thrombospondin-related anonymous protein. The averaged Robson and Chou-Fasman secondary structure predictions show that there are 57-66% turn and 19-38% beta-sheet structures in the typical repeat motif. The high amount of turn structure is consistent with Gly, Pro, Cys, and Ser being the four most abundant amino acid residues in properdin. Comparisons with sequences found in the circumsporozoite protein from several species of malaria parasites show that their sequences and secondary structures strongly coincide only in a 18-residue segment. Further secondary structure analysis utilized Fourier transform infrared spectroscopy of human properdin in 2H2O buffers. These show a broad amide I band that, after second-derivative and deconvolution calculations, is shown to be composed of several components. Two at 1633 and 1683 cm-1 are strong evidence for beta-sheet structure, although overlap from beta-turns can also contribute. The presence of beta-turn structure is indicated by absorptions at 1662-1675 and 1645 cm-1. The properdin structure contains substantial quantities of beta-sheet and beta-turn structures, which is consistent with the secondary structure predictions and amino acid compositions. The length of the repeat motif is estimated as 3.3-4.3 nm, and an estimated 14-22% of nonexchanged amide protons reside in properdin. This is suggestive of a high degree of solvent accessibility in the structure.

Amino Acid Sequence↗
PubMed1989

Stabilization of detergent-solubilized Ca2+-ATPase by poly(ethylene glycol).

The (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum (SR) has been solubilized with 1-alkanoyl propanediol-3-phosphorylcholines with chainlengths ranging between 8 and 12 C atoms. A marked dependence of the ATPase activity upon the chainlength was found, indicating that alkyl chainlengths with 12 C atoms are necessary for retention of activity. Addition of poly(ethylene glycol) to the eluting buffers used for gel filtration of the ATPase-detergent micelles was found to increase the activity and the long-term stability significantly. In the presence of Ca2+, the elution volume indicated an ATPase dimer, whereas in the absence of Ca2+ the elution volume indicated a monomeric solution. The purity of the preparations after gel filtration was improved by subsequent chromatography with a hydroxyapatite column.

Animals↗
PubMed1989

The effects of calcium, temperature and phospholamban phosphorylation on the dynamics of the calcium-stimulated ATPase of canine cardiac sarcoplasmic reticulum.

Highly purified sarcoplasmic reticulum (SR) has been prepared from dog hearts and has been incubated with the triplet probe erythrosinyl isothiocyanate to specifically label the Ca2+-stimulated ATPase (Ca2+-ATPase) of the SR. The rotational mobility of the Ca2+-ATPase has been studied in this erythrosin-labelled SR using time-resolved phosphorescence polarization. Qualitatively, the mobility of the cardiac Ca2+-ATPase resembles that of skeletal muscle SR Ca2+-ATPase. Addition of Ca2+ to SR affects the mobility of the Ca2+-ATPase in a way consistent with a segment of the ATPase altering its orientation relative to the plane of the membrane. Phosphorylation of phospholamban in cardiac SR by the purified catalytic subunit of cAMP-dependent protein kinase, which is known to increase the activity of the Ca2+-ATPase by deinhibition, also alters measured anisotropy. The changes observed are not compatible with dissociation of the Ca2+-ATPase from phospholamban after the latter is phosphorylated. The data are more consistent with phospholamban associating with the Ca2+-ATPase following phosphorylation, or more complex models in which only the hydrophilic domain of phospholamban binds with and dissociates from the Ca2+-ATPase.

Animals↗
PubMed1989

Fourier transform infrared spectroscopic investigation of rhodopsin structure and its comparison with bacteriorhodopsin.

FT-IR spectroscopy has been used to investigate the conformation of rhodopsin in bovine rod outer segment membranes, dispersed in aqueous suspension in both 2H2O and H2O. Detailed analysis of the amide I band was made, using second-derivative and deconvolution procedures. The frequency of the major amide I component is consistent with the presence of predominantly alpha-helices within the rhodopsin structure. A spectroscopic change occurs at acidic pH with the membranes in both 2H2O and H2O. The results for the membranes dispersed in H2O at pH 7 were used to estimate a value of 0.67 for w (amide II/amide I intensity ratio in H2O). This value of w gives an estimate of the unexchanged amide protons, in rhodopsin, of 51%. The extent of amide proton exchange at acidic p2H (p2H 5 and 2), in 2H2O was also determined. The conformation of rhodopsin in its unbleached and bleached states was investigated but no significant difference in the secondary structure was observed. A comparison, after second-derivative and deconvolution analysis, of the spectra of rhodopsin with that of bacteriorhodopsin shows that both proteins exhibit a similar number of amide I components. However, with bacteriorhodopsin the amide I band occurs at a higher frequency. Bacteriorhodopsin under similar conditions, in 2H2O, has 20% more unexchanged amide protons than does rhodopsin.

Animals↗
PubMed1989

Fourier transform infrared spectroscopic studies on the secondary structure of the Ca2+-ATPase of sarcoplasmic reticulum.

Fourier transform infrared spectroscopy has been applied to the study of the secondary structure of the Ca2+-ATPase of sarcoplasmic reticulum. An attempt is made to quantitatively assess the various secondary structures present. Values of 45% alpha-helix, 32% beta-sheet and 23% turns were obtained. A comparison is made of these results and those obtained using other techniques such as CD and Raman spectroscopy. The various assumptions inherent in the present procedure are discussed. The effect of various ligands, e.g. Ca2+, vanadate, ATP and phosphate, upon the structure were investigated. Upon binding these ligands no marked spectral changes were observed.

Animals↗
PubMed1989

Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma.

The value of secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma is not established. Sixty-seven patients with residual carcinoma found at the time of second-look laparotomy performed at Memorial Sloan-Kettering Cancer Center between December 1, 1978, and May 30, 1986, were evaluated for survival relative to the success of secondary cytoreductive surgery. At second-look laparotomy, 17 patients had microscopic disease, 28 patients had disease less than 2 cm and 22 patients had disease greater than 2 cm. After secondary cytoreductive surgery 33 patients had microscopic disease, 26 patients had disease less than 2 cm, and 7 patients had disease greater than 2 cm (1 unknown). Five-year survival by Kaplan-Meier calculation was 62% for patients found to have microscopic disease at second-look laparotomy and 51% for patients whose disease was rendered microscopic by secondary cytoreductive surgery (P = 0.55). Patients left with gross disease (either less than or greater than 2 cm) had 5-year survivals of less than 10% (P = 0.013 compared with microscopic residual). Secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma may result in improved survival of patients who are reduced to microscopic residual disease.

Adult↗