Search PubMed⌕ Search

Biomedical subjects

J J Lewis

Publications and source records attributed to J J Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1989

Decreased parietal cell secretory capacity following vagotomy and pyloroplasty.

Although vagotomy reduces acid secretion in vivo, the effects of vagotomy at the level of the parietal cell are not known. In the present study we examined the in vitro secretory characteristics of parietal cells in rabbits 8 weeks following vagotomy compared to unoperated and sham-operated controls. Acid secretion was assessed by the uptake of [14C]aminopyrine (AP) in isolated gastric glands. Also, gastric fundus histology, mucosal thickness, parietal cell density, and gastric gland somatostatin content were examined. Basal AP uptake was decreased following vagotomy (8 +/- 0.4 pmole/mg dry wt) compared to controls (21 +/- 2) (P less than 0.001). Increase in AP uptake by the cholinergic agonist carbachol was unaffected after vagotomy (P greater than 0.5) suggesting intact muscarinic receptors and calcium second messenger system. Increase in AP uptake was significantly reduced following vagotomy by the cyclic AMP-mediated agonist histamine (P less than 0.05) and the cyclic AMP mimetic 8-bromo cyclic AMP (P less than 0.001) suggesting an alteration in the ability of the parietal cell to utilize cAMP following vagotomy. There were no discernible differences in histology, mucosal thickness, or parietal cell number in vagotomized animals compared to controls (P greater than 0.5). There was a significant increase in gastric gland somatostatin content following vagotomy (37 +/- 10 fmole/mg dry wt) compared to control (14 +/- 1.5) (P = 0.025). These results suggest that there is a decrease in the capacity of parietal cells to secrete acid following vagotomy. In addition, the decrease in cAMP utilization following vagotomy suggests that the cAMP second messenger system is dependent, at least in part, on an intact vagus nerve.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Hypergastrinemia after vagotomy is not associated with decreased gastric somatostatin.

Although hypergastrinemia occurs after vagotomy, the mechanisms responsible are not understood. Somatostatin (SRIF) is a peptide that inhibits gastrin release, is present within the gastric fundus and antrum, and is under vagal control. In this study we have investigated the hypothesis that hypergastrinemia is associated with a decrease in gastric SRIF. We examined tissue levels of SRIF in gastric mucosa and muscle wall in rabbits undergoing vagotomy and pyloroplasty compared with sham-operated controls. We also compared the release of SRIF from gastric glands in response to vasoactive intestinal peptide and calcitonin gene-related peptide. Vagotomy resulted in an increase in gastrin compared with controls in both antrum (1062 +/- 176 pmol/gm vs 484 +/- 48 pmol/gm) and plasma (236 +/- 72 pmol/L vs 29 +/- 4 pmol/L; p less than 0.05). This was accompanied by an increase in the number of gastrin cells (25 +/- 4 vs 9 +/- 3; p less than 0.05). No significant differences were observed in gastric SRIF levels in either the fundus or antrum (p greater than 0.5). In addition, there were no differences in the release of SRIF from gastric glands of vagotomized animals compared with controls in response to vasoactive intestinal peptide and calcitonin gene-related peptide (p greater than 0.5). These data suggest that the elevations in plasma and antral gastrin levels after vagotomy are not a result of alterations in gastric SRIF.

Animals↗
PubMed1988

Pancreastatin: a novel peptide inhibitor of parietal cell secretion.

Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of 14C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10(-10) to 10(-6) mol/L) had no effect on 14C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10(-6), 10(-5) mol/L; p less than 0.005) and carbachol-(10(-5), 10(-4) mol/L; p less than 0.001) stimulated 14C-AP uptake in a dose-dependent manner. Neither forskolin-(10(-6), 10(-4) mol/L; p greater than 0.50) or 8-Br-cAMP-(10(-5), 10(-4) mol/L; p greater than 0.30) stimulated 14C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol-stimulated 14C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Mechanism of slow-binding inhibition of human leukocyte elastase by trifluoromethyl ketones.

Kinetics of inhibition have been determined for the interaction of human leukocyte elastase (HLE) with two series of peptide trifluoromethyl ketones (TFMKs): X-Val-CF3,X-Pro-Val-CF3,X-Val-Pro-Val-CF3, and X-Lys(Z)-Val-Pro-Val-CF3, where X is MeOSuc or Z. These compounds are "slow-binding" inhibitors of HLE and, thus, allow the determination of Ki, the dissociation constant for the stable complex of inhibitor and enzyme, as well as kon and koff, the rate constants for formation and decomposition of this complex. Maximal potency is reached with Z-Lys(Z)-Val-Pro-Val-CF3, which displays a Ki less than 0.1 nM. Upon binding to HLE, these compounds undergo addition by the hydroxyl of the active site serine to form a hemiketal. The evidence supporting a hemiketal intermediate includes Ki values of 1.6 and 80,000 nM for Z-Val-Pro-Val-CF3 and its alcohol analogue, linear free energy correlations between inhibitory potency and catalytic efficiency for structurally related TFMKs and substrates, and the pH dependence of kon for the inhibition of HLE by Z-Val-Pro-Val-CF3, which is sigmoidal and displays a pKa of 6.9. Hemiketal formation is probably not rate limiting, however. Kinetic solvent isotope effects of unity suggest that kon cannot be rate limited by a reaction step, like hemiketal formation, that is subject to protolytic catalysis. A general mechanism that is consistent with these results is one in which formation of the hemiketal is rapid and is followed or preceded by a slow step that rate limits kon.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMedDate not supplied

Immunotherapeutic approaches to sarcoma.

In the last decade, the most important factor in the rekindled interest in immune therapy for cancer is the development of new methods to identify tumor antigens that can be recognized by T-cells and other immune effectors. In addition, greater knowledge about tolerance and mechanisms of tumor cell evasion from immune effectors has made the prospect of developing clinically effective immune therapies for cancer seem promising. Research in immune therapies for sarcoma has been limited, mainly because of the previous lack of defined tumor antigens in this disease and the low prevalence of sarcoma in the general population. We will review the fundamental concepts of tumor immunobiology, both cellular and humoral, and highlight the new, powerful methods for identifying novel tumor antigens. Further, we will focus on the unique situation presented by sarcoma as the only solid tumor in which many cytogenetic abnormalities have been characterized which encode for unique, tumor-specific fusion proteins that are ideal targets for immune-based therapy. We will review the specifics of vaccine therapy approach to this disease, with emphasis on strategies to improve the immunogenicity of newly defined tumor antigens in sarcoma.

Antigens, Neoplasm↗
PubMedDate not supplied

Multifocal extremity sarcoma: an uncommon and controversial entity.

BACKGROUND: The primary site of metastasis from extremity sarcomas is the lung. When patients with extremity sarcoma present with the disease in more than one site but not in the lung, the question of whether the disease is multifocal or metastatic is difficult to resolve. METHODS: We reviewed 1423 patients admitted with extremity sarcoma from 1982 through 1996. Patient demographics, primary site, other sites, local recurrence, distant metastasis, and survival were analyzed. Statistics were by Fischer exact test, chi 2, Kaplan-Meier method, and log-rank test where appropriate. RESULTS: Sixteen (1%) patients were identified with multifocal disease out of 1423 patients with extremity sarcoma. There was no difference in sex, age, size, grade, depth, and margins between multifocal and unifocal disease. In a mean follow-up time of 57 months, 50% had local recurrence of primary tumor, 80% had distant metastasis, and only 30% were alive at the time of the analysis. Whereas 21% of all patients with solitary disease develop lung metastasis, 63% of patients with apparent multifocal disease develop lung metastasis. The 5-year disease-specific survival of patients with multifocal disease was not different from that of all patients presenting with metastatic disease to lung. CONCLUSION: Whether multifocal disease exists or is merely a form of metastasis is unproven by this analysis, but the outcome is the same. Management algorithms should suggest treating patients with multifocal disease as if it is metastatic disease.

Disease-Free Survival↗
PubMedDate not supplied

Superficial extremity soft tissue sarcoma: an analysis of prognostic factors.

BACKGROUND: Experience with soft tissue sarcoma has suggested that superficial tumors have a favorable prognosis. We evaluated the prognostic features of this subset of sarcoma. METHODS: Prospective data on 215 patients presenting to Memorial Sloan-Kettering Cancer Center with primary extremity superficial soft tissue sarcomas between July 1, 1982 and July 1, 1996 were analyzed. Superficial sarcomas were defined as subcutaneous tumors not invading the investing fascia of the muscle. Analysis was by univariate and multivariate tests for local recurrence, metastasis, and tumor mortality. RESULTS: Ninety (42%) patients were over 50 years of age, 115 (53%) had high-grade tumors, 53 (25%) had tumors > or = 5 cm, and 18 (8%) had positive margins following definitive resection. Median follow-up was 45 months (range 2 days to 151 months), 31 (14%) patients had local recurrences, 20 (9%) had distant metastases, and 15 (7%) died of disease. Five- and 10-year actuarial disease-specific survivals were 91% and 85%, respectively. On multivariate analysis, age > 50 years predicted local recurrence (RR 5.7; 95% CI, 2.4-13.3; p < 0.0001). High grade (RR 4.2; 95% CI, 1.4-12.7; p < 0.006), and size > or = 5 cm (RR 4.4; 95% CI, 1.8-11; p < 0.002) predicted distant metastases. High grade (RR 7; 95% CI, 1.5-31.4; p < 0.003), size > or = 5 cm (RR 6.9; 95% CI, 2.3-20.8; p < 0.0006), and positive margins (RR 3.8; 95% CI, 1.2-12.4; p < 0.006) predicted tumor mortality. CONCLUSION: Primary superficial extremity soft tissue sarcomas have a favorable prognosis. Size and grade of superficial tumors are the strongest factors in predicting survival.

Adolescent↗
PubMedDate not supplied

Neovascularity and clinical outcome in high-grade extremity soft tissue sarcomas.

BACKGROUND: Increased tumor neovascularity has been shown to correlate with poor prognosis in solid tumors. METHODS: Microvessels were identified by factor VIII immunohistochemical staining. Analysis of microvessel counts, tumor characteristics, and resection details was performed on 119 primary, high-grade extremity soft tissue sarcomas (STS) and correlated with clinical outcome. RESULTS: Tumor characteristics and resection details were analyzed and patient outcome was examined with respect to local recurrence, distant metastasis, and disease-specific survival. Factors found to be significant on univariate analysis for all outcome variables were positive microscopic margin and tumor size. A positive microscopic margin was found to be a significant risk factor for local recurrence (P = .03), distant metastasis (P = .006), and disease-specific survival (P = .004). A primary tumor greater than 10 cm in diameter was a poor prognostic factor for distant metastasis (P = .03) and disease-specific survival (P = .006) when compared to tumors smaller than 10 cm. Microvessel count did not correlate with survival nor did it predict distant metastasis or local recurrence. Histologic subtypes of STS that have a prominent vascular pattern as a diagnostic criterion (i.e., angiosarcoma, liposarcoma, hemangiopericytoma) form a subgroup of all STS. Neovascularity in these subtypes showed no relationship to clinical outcome. CONCLUSIONS: These data confirm the prognostic importance of microscopic margin and tumor size in high-grade extremity STS. Neovascularity measured by factor VIII staining had no prognostic significance in these mesenchymal tumors, in contradistinction to carcinomas. Alternatively, microvessel counts may not accurately represent the angiogenic capacity of STS. Therefore, patients with STS who are eligible for anti-angiogenesis clinical trials cannot be identified solely by microvessel count.

Adult↗
PubMedDate not supplied

Core needle biopsy for diagnosis of extremity soft tissue sarcoma.

BACKGROUND: Classic teaching has advocated the use of open biopsy to diagnose and grade extremity soft-tissue sarcoma. Reported advantages of core needle biopsy include the minimal morbidity, cost, and time. The perceived disadvantage has been diagnostic inaccuracy. The objective of this study was to compare the diagnostic accuracy of core needle biopsy to incisional or frozen section biopsy for primary extremity masses suspicious for soft-tissue sarcoma. METHODS: Patients presenting with extremity masses were identified from our prospective soft-tissue sarcoma database (malignant) and from the clinical information center (benign) between January 1, 1990, and December 31, 1995. Biopsy and subsequent resection data were collected from the pathologic records. RESULTS: During this time, 164 primary extremity soft-tissue masses were evaluated before any biopsy. As the initial diagnostic approach, there were 60 core needle, 44 incisional, 36 frozen section, and 26 excisional biopsies. Two patients underwent two biopsy procedures. Ninety-three percent of the specimens obtained at core needle biopsy were adequate to make a diagnosis. Of the adequate core needle biopsy specimens, 95%, 88% and 75% correlated with the final resection diagnosis for malignancy, grade, and histologic subtype, respectively. Of the frozen section biopsy specimens, 94% were adequate, and accurate diagnostic results of malignancy were obtained with 88%. However, only 62% and 47% were correct for grade and histologic subtype, respectively, which was significantly different than the results obtained with incisional biopsy. The false-negative and false-positive rates for core needle biopsy were 5% and 0% for malignancy. Two core needle biopsy specimens graded low were found to be high, and one core needle biopsy specimen graded high was subsequently found to be low on final resection. CONCLUSIONS: When read by an experienced pathologist, the results of core needle biopsy provide accurate diagnostic information for malignancy and grade. Adequate core needle biopsy obviates the need for open biopsy and can be used for rational treatment planning. In the absence of adequate tissue, open biopsy is required.

Biopsy, Needle↗
PubMedDate not supplied

Lymphatic mapping in the management of melanoma in children.

Lymphatic mapping allows the surgeon to identify and remove the first draining (sentinel) lymph node from a primary melanoma with minimal morbidity. The procedure facilitates accurate staging and identification of patients in need of additional therapy. We used lymphatic mapping and sentinel lymph node biopsy in two children with melanoma. Both patients had evidence of metastatic melanoma in their sentinel lymph nodes and underwent regional lymphadenectomy. Malignant melanoma and atypical pigmented lesions in children remain diagnostically challenging for the pathologist and clinician. Misdiagnoses occur, and the correct interpretation of a melanocytic tumor is too often made only after recurrence or metastasis has occurred. The use of lymphatic mapping facilitates accurate staging and identifies children in whom additional therapy may be indicated. In addition, it can assist in the assessment of the biologic potential of a difficult lesion.

Adolescent↗
PubMedDate not supplied

Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.

BACKGROUND: Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. METHODS: Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. CONCLUSIONS: Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.

Adolescent↗
PubMedDate not supplied

Determination of ractopamine hydrochloride in swine, cattle, and turkey feeds by liquid chromatography with coulometric detection.

A liquid chromatographic method is described for the determination of ractopamine hydrochloride (LY31537) in swine, turkey, and cattle feeds in the 1.25-100 ppm range and in swine supplement at 100 ppm. Feed samples were extracted with acidified methanol. An aliquot of the feed extract was diluted with water and buffered to pH 10.5 +/- 0.5 with sodium carbonate to convert ractopamine hydrochloride to a free base. The free base was extracted from the buffered sample with ethyl acetate. The extract was further purified on an acid-washed, silica solid-phase extraction cartridge. After conversion of the free base back to the salt form with pH 4.5 buffer, analytical separation and quantitation of ractopamine hydrochloride were accomplished on IBM phenyl and Whatman ODS reversed-phase columns with coulometric detection at +600 mV. Mean daily recovery levels ranged from 85 to 100% for feeds fortified at 1.25 to 100 ppm. The coefficients of variation ranged from 1 to 6% for feeds fortified at 2.5 to 100 ppm.

Adrenergic beta-Agonists↗