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Biomedical subjects

T Rich

Publications and source records attributed to T Rich.

At least 37 records · Page 2Linked to original sources
PubMed1997

HLA class II-induced translocation of PKC alpha and PKC beta II isoforms is abrogated following truncation of DR beta cytoplasmic domains.

Several studies have attempted to identify regions of the MHC class II molecule that participate in signal transduction. The importance of intact murine I-A cytoplasmic domains, either to tether the class II molecule to the cytoskeleton or to recruit signal-transducing proteins, is now well established. Recent data have also suggested that residues of the I-A beta transmembrane are involved in a second distinct signaling pathway. In the light of data suggesting that the second messengers activated on ligation of human and mouse class II molecules may differ, we set out to investigate whether the structural requirements for signaling for the human DR molecule are similar to those already described for the murine I-A molecule. We show that mutant DR class II molecules lacking 12 amino acids of the beta-chain cytoplasmic tail fail to translocate the protein kinase C alpha (PKC alpha) and PKC beta II isoenzymes following stimulation with an anti-class II mAb. In contrast, truncation of either or both cytoplasmic domains of the DR molecule has no effect on class II-induced tyrosine kinase activity. PKC translocation following class II stimulation has been observed in both human and murine B lymphocytes, whereas tyrosine kinase activation is present in human B lymphocytes but absent in resting murine B lymphocytes. Therefore, we conclude that the DR beta cytoplasmic tail is requisite for the principal signaling pathway initiated via MHC class II. These data suggest that the signaling pathways seen in resting vs primed murine B cells may also operate in human APCs.

Amino Acid Sequence↗
PubMed1997

Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with extrahepatic bile duct cancer remains poor. The purpose of this study was to evaluate our initial results with preoperative chemoradiation for extrahepatic cholangiocarcinoma, in the context of our experience with conventional treatment of this disease over the past 13 years. METHODS: From 1983 through 1996, analysis of all patients treated for extrahepatic cholangiocarcinoma was performed. RESULTS: Of 91 total patients, 51 had unresectable disease and 40 underwent resection. Median survival was significantly different for patients who underwent resection (22.2 months) versus those treated palliatively (10.7 months; P <0.0001). Nine patients underwent preoperative chemoradiation (5 perihilar, 4 distal) prior to resection. Three patients in the preoperative chemoradiation group had a pathologic complete response, while the remainder showed varying degrees of histologic response to treatment. The rate of margin-negative resection was 100% for the preoperative chemoradiation group versus 54% for the group who did not receive preoperative chemoradiation (P <0.01). There were no major intra-abdominal complications in the patients treated with preoperative chemoradiation. CONCLUSIONS: These results suggest that preoperative chemoradiation for extrahepatic bile duct cancer can be performed safely, produces significant antitumor response, and may improve the ability to achieve tumor-free resection margins. Additional trials of preoperative chemoradiation are warranted.

Adult↗
PubMed1997

Two widely used anti-DR alpha monoclonal antibodies bind to an intracellular C-terminal epitope.

In this report we show that two widely-used monoclonal antibodies, TAL-1B5 and DA6.147, which react with the HLA-DR alpha chain on immunoblots, recognize the C-terminal intracellular tail of this HLA-DR subunit. We demonstrate that both MoAbs react with a synthetic peptide representing the intracellular C-terminal tail of the DR alpha chain and that mutant DR molecules lacking this part of the alpha chain lose reactivity with TAL-1B5 and DA6.147, both in Western blot analysis and in intracellular FACS staining.

Amino Acid Sequence↗
PubMed1996

RTVP-1, a novel human gene with sequence similarity to genes of diverse species, is expressed in tumor cell lines of glial but not neuronal origin.

A novel gene, RTVP-1, which shows significant sequence identity to the mammalian testis-specific proteins, a family of plant pathogenesis-related proteins and the vespid venom allergen, antigen-5, has been isolated from a cDNA library of the human glioblastoma brain tumor cell line, U-251 MG. The highest degree of sequence identity was with the human testis-specific protein, TPX1 (38.7% over 119 amino acids). Northern hybridization analysis revealed that in fetal tissue RTVP-1 RNA was detected only in the kidney, but its expression was ubiquitous in adult tissues including brain. Multiple mRNAs encoded by RTVP-1 were highly expressed in a panel of cell lines from nervous system tumors arising from glia, although expression was low or absent in nonglial-derived nervous system tumor cell lines.

Amino Acid Sequence↗
PubMed1996

Orphan drug policy.

Explore the source record for details and available documents.

Orphan Drug Production↗
PubMed1994

Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma.

BACKGROUND: Rectal carcinoma tends to recur locally, with invasion of adjacent organs and significant pelvic pain. Both radiation therapy alone and combined chemoradiation have been used in an attempt to decrease the local recurrence rate and thereby improve survival. Although preoperative chemoradiation can clinically downstage rectal tumors, the pathologic extent of the residual disease has not been studied. METHODS: Thirty-seven patients with T3 rectal cancer diagnosed by transrectal ultrasonography (uT3) received 45 Gy with continuous infusion 5-fluorouracil (300 mg/m2/day). Proctoscopy with mucosal/submucosal biopsy was performed in patients (16 of 37) posttreatment and before definitive surgery. RESULTS: Microscopic evaluation of the 37 resected specimens showed a 30% (11 patients) pathologic complete remission rate. The pattern of residual disease in the remaining 26 patients showed that nine (25%) had microscopic residual tumor without evidence of mucosal involvement. Of the 14 patients with a negative proctoscopic evaluation and biopsy only, five (36%) had no residual tumor on final pathology. CONCLUSIONS: After chemoradiation, the pathologic presentation of rectal cancer may be altered, making endoscopic procedures and mucosal/submucosal biopsies unreliable in detection of residual disease. Despite the relatively good pathologic complete remission rate noted in this study, all patients undergoing chemoradiation for uT3 rectal carcinomas need definitive surgical resection to confirm a complete clinical remission.

Adenocarcinoma↗
PubMed1993

An attempt to modify unhealthful eating attitudes and weight regulation practices of young adolescent girls.

This is the first long-term, controlled study evaluating the effectiveness of a prevention curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls. Nine hundred sixty-seven sixth and seventh-grade girls were randomized to experimental healthy weight regulation curriculum or no-treatment control classes. A prevention intervention was developed around three principal components: (1) Instruction on the harmful effects of unhealthful weight regulation; (2) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity; (3) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting. The intervention failed to achieve the hoped-for impact. We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only, there was a small albeit statistically significant effect on body mass index. These findings question the wisdom of providing a curriculum directed at all young adolescents, most of whom are not at risk to develop an eating disorder. Rather than targeting the entire population, a healthy weight curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls might better focus on "at risk" students.

Adolescent↗
PubMed1993

A comparative study of the in-vitro activity of cefepime and other antimicrobial agents against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.

Using the national surveillance programme of USA hospitals, we selected 162 strains of Streptococcus pneumoniae for sensitivity testing using the NCCLS breakpoints for benzylpenicillin and the oxacillin discs screen test. Included in the group of isolates were 85 relatively penicillin-resistant and 33 penicillin-resistant strains. The activity of cefepime, a new cephalosporin, was compared with other cephalosporins and penicillins as well as some non-beta-lactam antimicrobials. Imipenem was the most active agent but, cefepime, cefotaxime, ceftriaxone and ciprofloxacin were only slightly less active. The least active agents were ceftazidime, cefuroxime, piperacillin/tazobactam and ticarcillin/clavulanate. Cefepime is a potential alternative treatment to penicillin, particularly when penicillin-resistant and relatively penicillin-resistant S. pneumoniae are encountered. The clinical importance of screening for penicillin resistance by the use of the oxacillin disc is emphasized.

Anti-Bacterial Agents↗
PubMed1993

In-vitro activity of cefepime and other antimicrobials: survey of European isolates.

Cefepime, a new cephalosporin which has a broad-spectrum of activity was tested in vitro against 1961 Gram-positive and Gram-negative clinical isolates obtained from European hospitals. Cefepime was highly active against Gram-negative organisms, inhibiting over 94% of strains tested. The overall susceptibility rate for cefepime against all isolates was 81%. Cefepime was more active than any of the third-generation cephalosporins tested against species capable of producing type I beta-lactamases, e.g. Enterobacter cloacae, Citrobacter freundii, and Enterobacter aerogenes. The activity of cefepime against Pseudomonas aeruginosa was similar to that of ceftazidime and substantially greater than those of cefotaxime and ceftriaxone. All cephalosporins except ceftazidime exhibited high activity against methicillin-susceptible Staphylococcus aureus but poor activity was observed against methicillin-resistant strains. Overall susceptibility to cefepime is lower in Europe than it is in North America.

Anti-Bacterial Agents↗
PubMed1990

Design of metallic electron beam cones for an intraoperative therapy linear accelerator.

A set of circular collimators and treatment cones from 5 to 12 cm diameter has been designed for an intraoperative accelerator (6-18 MeV) that has an optical docking system. Electron beam scattering theory has been used to minimize their weight while minimizing leakage radiation. Both acrylic and brass were evaluated as possible materials; however, because of substantial electron leakage through the lateral cone wall for acrylic, we have concluded that 2 mm thick brass walls are more desirable than acrylic walls. At 18 MeV, isodose measurements beneath the cones showed hot spots as great as 120% for both materials. The placement and dimension of an internal trimmer ring inside the brass cone was studied as a method for reducing the hot spots, and it was found this could only be accomplished at the expense of decreasing coverage of the 90% isodose surface. The effects of 1 degree cone misalignment on the dose distribution has been studied and found to generate changes of less than 5% in the dose and 3 mm in position of the 90% isodose surface. In a study of the contribution of the cone and its matching collimator assembly to x-ray room leakage, it was noted that although the treatment cone had a negligible contribution, the upper annuli of the upper collimator assembly contributed as much as 80% of the leakage at 16 MeV for the 5-cm cone.

Humans↗
PubMed1989

Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer.

As an alternative to radical surgery, local excision with or without adjuvant pelvic radiation therapy has been used in selected patients with rectal cancer. To determine which clinical and pathologic features can predict the presence of positive lymph nodes (LN+), a retrospective review of 168 patients who underwent potentially curative surgery for rectosigmoid and rectal cancer was performed. By univariate analysis, tumor penetration, grade, and histology were significant predictive features. This was confirmed by logistic regression analysis. The incidence of LN+ increased with increasing tumor penetration (T1, 0%; T2, 28%; T3, 36%; T4, 53%; P = 0.04), grade of adenocarcinoma (well-differentiated, 0%; moderately differentiated, 30%; poorly differentiated, 50%; P = 0.07, [borderline significance]), and the presence of any colloid histology (pure adenocarcinoma, 30%; total colloid, 52%; P = 0.04). Using 2 X 2 contingency tables, the presence of blood vessel invasion (BVI), lymphatic vessel invasion (LVI), vascular invasion (VI), total colloid histology, and high grade further increased the incidence of LN+ with increasing tumor penetration. Regardless of tumor size, grade, histology, BVI, LVI, or VI, none of the nine patients with Stage T1 tumors or the seven with well-differentiated adenocarcinomas had LN+. For this group, local excision alone is recommended. The incidence of LN+ was greater than or equal to 19% in all other categories. For this group of patients, if there is no evidence of gross tumor in the pelvis, then a local excision plus adjuvant pelvic radiation may be an alternative to radical surgery.

Adenocarcinoma↗
PubMed1989

The Stanford Adolescent Heart Health Program.

This study was designed to create, implement, and test a school-based multiple risk factor reduction program for high school students. All tenth graders in four senior high schools (N = 1447) from two school districts participated in the study. Within each district, one school was assigned at random to receive a special 20-session CVD risk reduction intervention and one school served as a control. The schools were matched for size and distribution of racial groups before randomization. At a two-month follow-up, knowledge gains were significantly greater for students in the treatment group on each of the risk factor domains tested: nutrition/diet (p less than 0.0001), physical activity (p less than 0.0001), and cigarette smoking (p less than 0.0001). Compared to controls, a higher proportion of those in the treatment group who were not exercising regularly at baseline, reported regular exercise at follow-up (p less than 0.0003). Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up while only 5.6% of baseline experimental smokers in the treatment group graduated to regular smoking compared to 10.3% in the control group (p = 0.009). Students in the treatment group were more likely to report that they would choose heart healthy snack items (p less than 0.0001). Beneficial treatment effects were observed for resting heart rate (p less than 0.0001), BMI (p = 0.05), triceps skinfold thickness (p = 0.003), and subscapular skinfold thickness (p = 0.01). The results suggest that it is feasible to provide CVD risk reduction training to a large segment of the population through school-based primary prevention approaches.

Adolescent↗
PubMed1988

Enamel of Yalkaparidon coheni: representative of a distinctive order of tertiary zalambdodont marsupials.

The enamel of an incisor and a premolar of Yalkaparidon coheni was examined by scanning electron microscopy in fractured and in sectioned, polished surfaces. The enamel of both teeth demonstrated: complete, ovoid and horse-shoe shaped prisms in a Pattern 2 arrangement; a simple parallel prism course; and, enamel tubules in abundance in the premolar but restricted to the innermost enamel in the incisor. Overall, the enamel ultrastructure supports the marsupial affiliation proposed for Yalkaparidon coheni but does not unambiguously ally it with any other order of marsupials. The observation of a significant ultrastructural difference between the anterior and posterior teeth of a marsupial emphasizes the need to sample both if available. In pursuing this, we report here also the lack of tubules in the anterior teeth of the extant Tarsipes rostratus. This together with a similar absence of typical marsupial tubules from the incisor of the extinct Yalkaparidon coheni, would suggest that the wombat is not the only surviving marsupial to have experimented so extensively with this particular structural feature. It is likely that further study will demonstrate an unexpected and relative lack of tubules in the incisor enamel of other fossil Australian marsupials.

Animals↗
PubMed1985

A cross-cultural look at the relationship between age and innovative behavior.

This study investigates the relationship of age to innovativeness when the effects of opportunity have been controlled. Data were obtained from the Basic Village Education Project. The analysis was conducted on two groups of farmers, the Spanish-speaking Ladino population found in Eastern Guatemala and the Quiche-speaking Mayan population found in the mountains of Western Guatemala. Each group was subdivided into young, middle age and old categories. Innovativeness was defined as the level of agricultural technology utilized by individual farmers at the end of the BVE-project period. A separate analysis was conducted for each culture and findings for both indicate that younger farmers were more likely than their older counterparts to adopt new agricultural practices when economic opportunity is controlled. These findings are of three fold importance: they indicate the importance of economic constraints to innovation; they contain implications for policies concerning target development programs, and they contain a warning about ethnocentric hypotheses in research related to "underdeveloped" countries.

Adolescent↗
PubMed1984

Complications of intraoperative radiation therapy.

The ability to demonstrate an improvement in therapeutic ratio is critical in assessing new treatment modalities; an evaluation of treatment complications is essential for this purpose. We have studied the severe complications occurring after treatment with intraoperative radiation therapy (IORT) in patients with locally advanced carcinoma of the rectum. Four groups of patients were compared: Group 1 (80 patients) had treatment with surgery alone for mobile and resectable tumors; Group 2 (23 patients) had treatment with high dose preoperative irradiation followed by surgical resection for tumors which were fixed to adjacent structures and initially unresectable for cure; Group 3 (24 patients, primary disease) and Group 4 (17 patients, locally recurrent disease) had locally advanced tumors as in Group 2 but were treated with IORT after preoperative irradiation and attempted surgical resection. All but 3 complications occurred within one year of therapy. Severe complications were seen in 16% of patients in Group 1, 35% in Group 2, 21% in Group 3 and 47% in Group 4 (32% in Groups 3 and 4 combined). There was a statistically insignificant increase (p = .10) in the complication rate in all irradiated patients (locally advanced tumors) compared to surgery alone (clinically mobile tumors). These data indicate no increase in severe complications with the use of IORT. If the ongoing studies continue to show improved local control with the use of IORT, expanded use of this modality may be warranted.

Adult↗
PubMed1983

Patterns of recurrence of rectal cancer after potentially curative surgery.

The results of surgical treatment alone for 142 cases of carcinoma of the rectum and rectosigmoid from the Massachusetts General Hospital were reviewed. The incidence of local failure as any component of failure was found to be strongly dependent on the pathologic stage, and for Dukes' A was 8.0% (3/39); Dukes' B, 31% (18/59), and Dukes' C, 50% (22/44). The incidence of local failure for tumors without lymph node metastasis was 17% with only microscopic extension through the wall (modified Astler-Coller Stage MAC-B2m), but increased to 54% in tumors that were adherent to or invading adjacent organs and structures (MAC-B3). Similarly, in tumors with positive lymph nodes, there was a 36% incidence of local failure for tumors confined to the wall or with only microscopic extension through the wall (MAC-C1/C2m), compared to a 67% incidence for tumors with adherence or involvement of adjacent organs (MAC-C3). Other predictors of local recurrence were the tumor location, grade, number of lymph nodes, and blood vessel invasion. The pathologic factors predicting distant metastasis are also presented. Five-year survival for Dukes' A was 77% (30/39); Dukes' B, 44% (26/59); and Dukes' C, 23% (10/44). The implications for future adjuvant therapy based on the identification of patients with the highest risk for local and distant failure are discussed.

Follow-Up Studies↗