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J Jenkins

Publications and source records attributed to J Jenkins.

At least 91 records · Page 5Linked to original sources
PubMed1995

Beta-glucosidase, beta-galactosidase, family A cellulases, family F xylanases and two barley glycanases form a superfamily of enzymes with 8-fold beta/alpha architecture and with two conserved glutamates near the carboxy-terminal ends of beta-strands four and seven.

Comparison of the recently determined crystal structures Pseudomonas fluorescens subsp. cellulosa family F xylanase, (1-3)-beta-glucanase and (1-3,1-4)-beta-glucanase and the catalytic domain of E. coli beta-galactosidase reveals that they belong to a superfamily of 8-fold beta/alpha-barrels with similar amino acid residues at their active sites. In the three families that these enzymes represent, the nucleophile is a glutamate, which is located close to the carboxy-terminus of beta-strand seven. In addition all three enzymes have the sequence asparagine-glutamate close to the carboxy-terminus of beta-strand four. This glutamate has been identified as the acid/base in the family F xylanases and is essential for catalysis in beta-galactosidase. We suggest that the equivalent residue in the barley glucanases is the acid/base. Analysis of the sequences of family 1 beta-glucosidases and family 5 cellulases shows that these enzymes also belong to this superfamily which we call the 4/7 superfamily.

Amino Acid Sequence↗
PubMed1995

HPV-18 E6 mediated inhibition of p53 DNA binding activity is independent of E6 induced degradation.

A key activity of the p53 protein during suppression of cell growth is its ability to stimulate transcription from promoters of cellular genes which contain a p53 responsive element. The E6 proteins from the oncogenic associated Human Papillomaviruses (HPVs) have been shown to inhibit specifically the p53 transcriptional activation and this has been proposed as a mechanism whereby the virus prevents the suppression of cell cycle progression and the induction of apoptosis. However, the mechanism by which E6 exercises this function is unknown, as is the ability of E6 to associate with different oligomeric forms of p53. In this study we demonstrate that E6 induces changes within the p53 protein which result both in inhibition of DNA binding and in dissociation of p53 protein previously bound to the DNA. These activities correlate exactly with the ability of E6 to inhibit p53 transcriptional activation and are independent of the ability of E6 to direct the degradation of the p53 protein. Further, we show that E6 labels wild type tetrameric and dimeric forms of p53 proteins for ubiquitin mediated degradation more readily than monomeric forms of the protein. However, in vivo analyses indicate that E6 is capable of inhibiting the transcriptional activation induced by the tetrameric, dimeric and monomeric forms of p53.

Base Sequence↗
PubMed1995

DNA recombinase activity of eukaryotic DNA topoisomerase I; effects of camptothecin and other inhibitors.

DNA oligonucleotides containing a strong topoisomerase I cleavage site were used to study the DNA cleavage and strand transferase activities of calf thymus topoisomerase I (top1) in the absence and presence of camptothecin. A partially single-stranded oligonucleotide with only two nucleotides on the 3' side of the cleavage site (positions +1 and +2) was cleaved at the same position as the corresponding duplex oligonucleotide. However, cleavage in the absence of camptothecin was more pronounced than in the duplex oligonucleotide and was only partially reversible in the presence of 0.5 M NaCl, consistent with release of the dinucleotide 3' to the top1 break. Another reaction took place generating a larger DNA fragment which resulted from religation (strand transfer) of the 5'-hydroxyl terminus of the non-scissile DNA strand to the 3' end of the top1-linked oligonucleotide after loss of the +1 and +2 nucleotides. Top1 religation activity appeared efficient since only the last 5' base of the single-stranded DNA acceptor was complementary to the 3' tail of the donor DNA. Religation was not detectable with a double-stranded DNA acceptor, which is consistent with the persistence of top1-induced DNA double-strand breaks in camptothecin-treated cells. Camptothecin and other top1 inhibitors enhanced cleavage in both the partially single-stranded and the duplex oligonucleotides, indicating that they did not inhibit the induction of top1-mediated DNA cleavage but primarily blocked the religation step of the enzyme catalytic cycle. The top1 DNA strand transferase activity was reversibly inhibited by camptothecin and several derivatives, as well as saintopin. These results are discussed in terms of camptothecin-induced DNA recombinations.

Animals↗
PubMed1995

New Lithostar treatment technique for difficult upper ureteral stones.

In situ treatment of ureteral stones with the Siemens Lithostar is highly successful. In a rare patient, however, despite various positioning maneuvers, an upper ureteral or lower pole renal stone overlies vertebral bone when the shock head is raised. Unless the patient chooses to delay treatments until the stone has moved distally, such patients would ordinarily be forced to undergo percutaneous stone manipulation or ureteroscopy. We describe a technique to facilitate in situ Lithostar treatment of these uncommon but vexing upper ureteral stones using the contralateral shock head with stone side-posterior oblique positioning. Nine of ten patients were stone free at 3 months without further treatment.

Equipment Design↗
PubMed1995

Stereotactic injection of herpes simplex thymidine kinase vector producer cells (PA317-G1Tk1SvNa.7) and intravenous ganciclovir for the treatment of progressive or recurrent primary supratentorial pediatric malignant brain tumors.

This study will evaluate the safety and efficacy of in vivo gene transfer of the herpes simplex thymidine kinase (HSV-Tk1) gene using PA317/G1Tk1SvNa.7 vector producer cells (VPC) in pediatric patients with progressive or recurrent primary supratentorial malignant brain tumors. Insertion of the HSV-Tk1 gene confers a sensitivity to the anti-herpes drug ganciclovir. It has been demonstrated that the direct injection of HSV-Tk vector producer cells into growing tumors in animals can result in their complete destruction with ganciclovir therapy. This selective destruction of growing tumors in situ is thought to result from the transfer of the HSV-Tk gene into the tumor cells and the production of toxic ganciclovir metabolites which result from the interaction of HSV-Tk and ganciclovir. This procedure can result in the cure of some experimental animals with limited systemic toxicity due to selective gene transfer into tumors. This clinical trial will focus on maximizing the relative number of vector producer cells to the tumor mass by stereotactically injecting VPCs into the tumor mass. Children with progressive or recurrent primary supratentorial malignant brain tumor which is accessible to stereotactic injection will be evaluated for the extent and location(s) of their disease before being entered into the study. Fifteen days after stereotactic injection of the tumor mass, ganciclovir will be administered at 5 mg/kg IV b.i.d. for 14 days. Upon completion of the treatment with HSV-Tk1 vector producer cells and ganciclovir, the patient will be followed monthly for the first three months, then every two months for the next twenty-one months, and annually for life thereafter.

Adolescent↗
PubMed1995

A hidden leak.

Explore the source record for details and available documents.

Equipment Failure↗
PubMed1995

Phase II trial of docetaxel in patients with advanced cutaneous malignant melanoma previously untreated with chemotherapy.

PURPOSE: A phase II study was undertaken to determine the efficacy of docetaxel in patients with metastatic malignant melanoma. PATIENTS AND METHODS: Between June 1992 and March 1994, 40 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg/m2 administered intravenously over 1 hour every 21 days. None of the patients had brain metastasis. Toxicity and follow-up data are provided. RESULTS: One patient had a histologically confirmed complete response that lasted for 14+ months. Four patients had partial responses, bringing the overall response rate to 12.5% (95% confidence interval [CI], 6% to 30%). A patient with a partial response had a single chest-wall metastasis and was rendered free of disease surgically after a maximal response to docetaxel and remained free of tumor recurrence after 18+ months. Tumor was stabilized in 22 patients. The overall median survival time was 13 months. The main hematologic toxicity was neutropenia, which was severe but transient. Peripheral neuropathy was the limiting nonhematologic toxicity in three patients. Other important toxicities included cutaneous toxicity, fluid retention, oral mucositis, and hypersensitivity reactions. Preadministration of dexamethasone and diphenhydramine reduced the incidence of hypersensitivity reactions, cutaneous toxicities, and fluid retention. CONCLUSION: Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be conducted in multidrug combination programs.

Adult↗
PubMed1995

Expression of the p53 gene and presence of serum autoantibodies in ovarian cancer: correlation with differentiation.

A study was carried out to assess the prognostic significance of significance of p53 expression in ovarian tumors. Archival material from 105 ovarian cancer biopsies was examined for the presence of the p53 protein by an immunoperoxidase technique using the cell-mediated immune (CMI) antibody. Employing a 3-point scale for intensity and the proportion of malignant cells positive, 26% of cases had a score of 4 to 6, 19% were 1 to 3, and 55% were negative. There was no correlation with response to therapy or survival at a median follow-up of 6 years, but a higher score was found to correlate with poor tumor differentiation (Spearman rank: p = 0.03). In a more recent series of 38 ovarian cancer patients, serum autoantibodies to the p53 protein were detected in 29% of cases by an ELISA technique compared with 1 out of 73 normal control women. In 19 of these cases, both serum and malignant tissues were negative, while in 7 of the 11 cases with positive sera, the tissue was also found to contain detectable p53 protein. We conclude that tissue expression of p53 in ovarian tumors is associated with poor histological differentiation and the presence of detectable serum autoantibodies.

Autoantibodies↗
PubMed1994

DNA topoisomerases I & II cleavage sites in the type 1 human immunodeficiency virus (HIV-1) DNA promoter region.

Topoisomerase sites were mapped in the 5'-long terminal repeat of HIV-1 DNA by agarose and sequencing gel electrophoresis. Topoisomerase II sites were observed in the absence and presence of teniposide and amsacrine in the transcription initiation region and the TATA box, consistent with a possible role of topoisomerase II in transcription. The NF-kB and Sp1 regions were poorly cleaved. Topoisomerase I sites were relatively unfrequent even in the presence of camptothecin. They were absent in the core promoter and were concentrated in the TAR and the upstream region near the junction with the host DNA.

Amsacrine↗
PubMed1994

Pulmonary insufficiency complicating therapy with high dose cytosine arabinoside in five pediatric patients with relapsed acute myelogenous leukemia.

BACKGROUND: The occurrence of fatal or nearly fatal pulmonary insufficiency in 5 of 22 pediatric patients with relapsed acute myelogenous leukemia (AML) treated with high dose cytosine arabinoside (Ara-C) at St. Jude Children's Research Hospital, Memphis, Tennessee, and institutions affiliated with the Pediatric Oncology Group (POG) is reported. METHODS: Cytosine arabinoside (1.0-1.5 g/m2/day) was given as a 5-day continuous infusion to all patients. Four patients with persistent leukemia received a second 3- or 5-day course. The POG protocol included the administration of granulocyte colony stimulating factor for the priming of myeloblasts. Diagnostic criteria for pulmonary insufficiency included noncardiogenic pulmonary edema with exclusion of underlying cardiorespiratory, infectious, or metabolic conditions. Autopsy material also was reviewed. RESULTS: Of the 22 patients 5 died (23%), including 2 who received a second course of Ara-C as a result of pulmonary insufficiency that developed at a median of 8 days (range, 3-38 days) after the first course. Three patients died despite intubation and pressor support. Two patients were managed successfully with colloids, diuresis, and oxygen by face mask; remission was achieved in both. The postmortem examination of one patient disclosed airless lungs, profound pulmonary edema, and subpleural nodules, but no evidence of leukemia. CONCLUSION: Pulmonary insufficiency from high dose Ara-C varies in severity and may be fatal. It may occur during or after treatment. Awareness of this potential complication, careful attention to fluid status, and aggressive supportive care may optimize outcome.

Acute Disease↗
PubMed1994

The suitability of automatic tissue morcellation for the endoscopic removal of large specimens in pediatric surgery.

UNLABELLED: Now that endoscopic removal of tumors and other solid structures from the abdomen and chest is possible, it is important to know the suitability of this technique for the removal of solid pediatric malignancies where accurate histological assessment becomes important for prognosis and staging. The authors tested an automatic tissue morcellator on a variety of pediatric tissues to assess the interpretability of the material obtained. The morcellator consists of a rotary blade within a 1-cm sleeve. When suction is applied to the morcellator and the device is activated, the solid material is shaved or morcellated into bits of tissue that are aspirated and collected for analysis. To test the interpretability of morcellated tissue, the device was used on six Wilms' tumors, three hepatoblastomas, a lung resection, a splenectomy, and a bowel resection. The average size of the pieces of tissue was 1.33 x 0.58 x 0.43 cm. In every instance, the histology was as good as the evaluation of sections from the gross tumor. It was difficult to distinguish the edge of tissue procured by the morcellator from an edge cut by the pathologist's knife. CONCLUSIONS: (1) Morcellated pediatric tissues are available by experienced pediatric pathologists. (2) The adoption of this technique should not interfere with proper histological evaluation of solid pediatric tumors.

Biopsy↗
PubMed1994

Parallel beta-domains: a new fold in protein structures.

A new type of structural domain, composed of parallel beta-strands folded into a coiled structure, has been observed in several protein structures within the past year. An analysis of the basic motif indicates that there are two distinct types, with variations likely to be discovered in the future.

Amino Acid Sequence↗
PubMed1994

Serum p53 auto-antibodies: incidence in familial breast cancer.

Inactivation of the p53 gene, which codes for a tumour suppressor protein, is known to occur in the majority of human malignancies. An ELISA technique has been developed which has detected auto-antibodies to p53 in the serum of 25.6% of 176 women with breast cancer, considerably higher than previously reported with an immunoblotting technique. The incidence of auto-antibodies in those cases with a family history of breast cancer was 9.1%, compared to 29.4% in those with no family history (P = 0.029). In women without clinical breast cancer, 4 out of 36 (11.1%) of those with a positive family history were seropositive, compared to 1 out of 73 control women. Auto-antibodies were more frequently seen in the serum of breast cancer patients whose biopsies demonstrated overexpression of p53 protein. We conclude that auto-antibodies to p53 may have a role in the molecular characterisation of familial breast cancer.

Adult↗
PubMed1994

The structure of Bacillus subtilis pectate lyase in complex with calcium.

We have solved the structure of the Bacillus subtilis pectate lyase (BsPel) in complex with calcium. The structure consists of a parallel beta-helix domain and a loop region. The alpha L-bounded beta-strand seen in BsPel is a new element of protein structure and its frequent occurrence suggests it is an important characteristic of the parallel beta-helix. A pronounced cleft is formed between the loops and the parallel beta-helix domain and we propose that this is the active site cleft. Calcium, essential for the activity of the enzyme, binds at the bottom of this cleft and an arginine residue close to the calcium, which is conserved across all pectin and pectate lyases, may be involved in catalysis.

Amino Acid Sequence↗
PubMed1994

Comparison of ampullary assessment by falloposcopy and salpingoscopy.

The purpose of this study was to compare and contrast falloposcopic and salpingoscopic ampullary assessments in a series of 20 women undergoing tubal microsurgery for distal tubal or peritubal disease. Four women had an extrinsic cause for their peritubal adhesions, and would have been expected to exhibit a normal oviductal canal. All of the falloposcopic examinations were performed as an outpatient procedure. Salpingoscopic examinations were undertaken at the time of microsurgery. The endoscopic examinations were undertaken by two clinicians, who were blinded to each other's assessments and to the indication for surgery. Of the 31 Fallopian tubes which were examined, 24 were found to be abnormal by salpingoscopy and 23 were found to be abnormal by falloposcopy. Total score and scores for epithelial appearance, vascularity, intraluminal adhesions and dilatation were found to be significantly associated. Furthermore, falloposcopy predicted salpingoscopic status correctly in 84% of cases. These data suggest that falloposcopy is a useful method of assessing ampullary condition.

Endoscopy↗
PubMed1994

Gene therapy for cancer.

Advances in molecular biology and technology now being made will open the way to using gene transfer as a therapeutic option for patients with cancer. Since there are > 5,000 known genetic diseases, the potential impact of these techniques is enormous. Possibilities for the application of gene therapy are emerging and along with them complex safety, ethical, and financial issues that will require resolution. Many of these concerns will become relevant to the oncology nurse, who will need to understand the science, ethics, safety considerations, and impact of this experimental therapy on the patient. Since gene therapy is a rapidly evolving method of treatment, it will be a challenge to remain up to date and knowledgeable.

Female↗
PubMed1994

Extension of epidural blockade for emergency caesarean section. Assessment of a bolus dose of bupivacaine 0.5% 10 ml following an infusion of 0.1% for analgesia in labour.

A safe and predictable method by which an epidural infusion sufficient for pain control in labour can be rapidly converted to a more intense block adequate for emergency Caesarean section continues to present a challenge. A prospective study was undertaken. The routine use of a bolus dose of 10 ml of 0.5% bupivacaine was assessed as a top-up for emergency Caesarean section following a 0.1% infusion for labour. This produced an adequate block in 11 out of 18 patients. There were no significant differences in duration of infusion, cumulative local anaesthetic dose or pre-existing block height in these patients when compared with the remaining seven patients who required an additional top-up.

Adolescent↗