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Biomedical subjects

J Jacob

Publications and source records attributed to J Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1995

A report on the use of technician ophthalmoscopy combined with the use of the Canon non-mydriatic camera in screening for diabetic retinopathy in the community.

This paper describes a general practice based diabetic retinopathy screening service employing a technician trained in direct and indirect ophthalmoscopy and taking photographs with a Canon CR3 45 NM non-mydriatic polaroid camera analysed by a consultant ophthalmologist to provide a comparison with the screener's opinion. Prospective data is presented from the first 1050 patients screened for diabetic retinopathy in the Exeter Health Authority area. Analysis of data collected showed a prevalence of diabetic retinopathy in the screened population of 27%, 14% previously undetected with a 0.5% prevalence of sight-threatening retinopathy. There was almost complete agreement between ophthalmoscopy findings and the consultant analysis of photographs. Screening costs were calculated at 10.38 pounds per patient screened. A specially trained non-medically qualified technician can provide a good quality cost-effective screening service for diabetic retinopathy within a primary care setting.

Adolescent↗
PubMed1995

Paclitaxel, cisplatin, and cyclophosphamide in human ovarian cancer: molecular rationale and early clinical results.

The three most active types of agents in the treatment of cancer of the ovary are platinum compounds (cisplatin or carboplatin), bifunctional alkylating agents (cyclophosphamide, melphalan, etc), and the recently developed natural product paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). In an effort to improve long-term disease-free survival in patients with advanced disease, we have developed a three-drug regimen consisting of cisplatin, paclitaxel, and cyclophosphamide. Granulocyte-colony stimulating factor is given as bone marrow support using a flexible dosing approach. The molecular basis for this approach is founded in the positive molecular interactions between cisplatin and bifunctional alkylating agents and between paclitaxel and DNA-damaging agents. Cisplatin and cyclophosphamide damage DNA by two very different mechanisms; the respective importance of DNA strand "kinking" versus DNA strand "cross-linking" may explain the positive cell kill interaction between these two drugs. Paclitaxel appears to markedly slow the repair of DNA lesions caused by DNA-damaging agents, which may include radiation-induced lesions, cisplatin adducts, and cyclophosphamide cross-links. Clinical data to date from several different groups strongly suggest that these molecular interactions translate into positive clinical benefit in human ovarian cancer. Preliminary data from our clinical trial show that these three agents are well tolerated in the doses administered and that this combination shows exceptional promise as a possible therapeutic advance in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Characterization of the sat4 gene encoding a streptothricin acetyltransferase in Campylobacter coli BE/G4.

The sat4 streptothricin resistance gene from Campylobacter coli BE/G4 was cloned into pUC18, and its nucleotide sequence was determined. Streptothricin acetyltransferase activity was detected in Escherichia coli cells containing recombinant plasmid pAT132 which carries the sat4 gene as an insert. The deduced amino acid sequence displayed 21-27% amino acid identity with streptothricin acetyltransferases from E. coli and streptothricin producers Streptomyces lavendulae and Streptomyces noursei. The sat4 gene was detected by hybridization in clinical and environmental isolates of Campylobacter spp.

Acetyltransferases↗
PubMed1993

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells.

In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared by day 4, mutation was not observed in germinal center B cells until day 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated until day 14. During this period, strong phenotypic selection on the mutant B lymphocytes was inferred from progressively biased distributions of mutations within the Ig variable region, the loss of crippling mutations, decreased relative clonal diversity, and increasingly restricted use of canonical gene segments. The period of most intense selection on germinal center B cell populations preceded significant levels of mutation and may represent a physiologically determined restriction on B cells permitted to enter the memory pathway. Noncanonical Ig genes recovered from germinal centers were mostly unmutated although they probably came from antigen-reactive cells. Together, these observations demonstrate that the germinal center microenvironment is rich and temporally complex but may not be constitutive for somatic hypermutation.

Animals↗
PubMed1993

Age does not influence taxol dose intensity in recurrent carcinoma of the ovary.

BACKGROUND: In the treatment of advanced-stage ovarian cancer, it is common practice to treat elderly patients in a less aggressive fashion than young patients. This approach is based on the notion that age is associated with poor patient tolerance to aggressive chemotherapy. Relatively little data exist to support this contention. The most exciting new chemotherapy agent to be developed in the last 10 years is taxol, a diterpeniod derivative of the Northwestern yew Taxus brevifolia. METHODS: The ability to administer dose-intensive taxol to adult patients with recurrent ovarian cancer was assessed retrospectively, and the question was asked whether the administered dose intensity of taxol was unfavorably influenced by age. Forty-eight patients with recurrent ovarian carcinoma received taxol at an initial dose of 250 mg/m2 every 3 weeks. Age in this cohort ranged from 26 to 74 years, with a median of 55. Twenty-nine percent (14 of 48) of the patients treated were 61 years of age or greater. Criteria for administration of taxol included a creatinine clearance of > 45 ml/minute, minimal abnormalities in liver function tests, good performance status, and the absence of substantial comorbid disease. RESULTS: Elderly patients in this cohort (age > 60 years) did not differ from younger patients with respect to administered dose intensity, number of cycles of therapy administered, or the occurrence of serious or mild toxicities.

Adult↗
PubMed1993

Selective neuronal cell attachment to a covalently patterned monoamine on fluorinated ethylene propylene films.

The patterned covalent surface addition of a monoamine to fluorinated ethylene propylene films (FEP) controls both cellular attachment and differentiation in defined media conditions. A radio frequency glow discharge (RFGD) process was used to replace FEP surface fluorine atoms with hydroxyl groups. The primary amine was then covalently attached by polymerizing aminopropyl-triethoxysilane (APTES) via the hydroxyl functionalities. The selective attachment of cells to the APTES regions was determined to be dependent upon the initial adsorption of albumin to the patterned FEP membrane. Albumin was determined to enhance cellular attachment to the APTES regions and prevent attachment to the unmodified FEP areas for both an NB2a neuroblastoma cell line and primary rat endothelial cells. If albumin were not preadsorbed onto the membrane, selective attachment to the modified regions would not occur. Radiolabeling albumin with 125I demonstrated the preference of albumin for adsorption onto the monoamine surface where the cells preferentially attached. Both hydrophobic and ionic forces contributed to the adsorption process. Although selective cellular attachment to the patterned APTES regions could be achieved by albumin preadsorption to the surface, the neuroblastoma cells did not significantly differentiate unless additional serum components were supplemented to the media.

Adsorption↗
PubMed1993

Biomonitoring of polycyclic aromatic hydrocarbons in highly exposed coke plant workers by measurement of urinary phenanthrene and pyrene metabolites (phenols and dihydrodiols).

A filter combination consisting of an impregnated glass fibre and a control filter was used for the collection of air samples in which gaseous and particulate polycyclic aromatic hydrocarbons (PAHs) were determined. To estimate the loss of lower boiling PAHs, d10-phenanthrene was applied as internal standard. A simple, well-producible method for the determination of 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1,2-, 3,4- and 9,10-dihydroxydihydrophenanthrene, 1-hydroxypyrene and 1,2-dihydroxy-1,2-dihydropyrene is described. By means of personal air samplers the exposure to PAHs of four coke plant employees working at different locations was measured over 4 days. Simultaneously the 24-h urine was collected and stored frozen until analysed. The main excretion product of pyrene is a 1-hydroxypyrene conjugate, whereas phenanthrene is excreted predominantly as dihydrodiol conjugate. As expected, workers on the battery topside were exposed the most and accordingly excreted by far the highest amounts of PAHs. Up to 34.0 micrograms phenanthrol conjugates (total of all isomeric phenols) and 195.5 micrograms dihydrodiol conjugates (total of all isomeric dihydrodiols) were excreted in the 24-h urine (mean of 4 days). The metabolite profiles of five isomeric phenanthrene phenols and three isomeric dihydrodiols exhibited only small percentage variations within one individual whereas significant interindividual differences were observed. These findings may indicate a genetically determined enzyme pattern responsible for the metabolic conversion of PAHs.

Air Pollutants, Occupational↗
PubMed1993

Covalent binding of polycyclic aromatic hydrocarbon components of coal tar to DNA in mouse skin.

Treatment of mouse skin with coal tar is known to initiate tumour formation, with the carcinogenic activity associated mainly with polycyclic aromatic hydrocarbons (PAHs). A sample of pharmaceutical coal tar was analysed by gas chromatography and 19 major PAHs were identified. 32P-postlabelling analysis was used to characterize those PAHs that are responsible for the DNA binding of coal tar and, by inference, its biological activity. PAHs were grouped according to their reported carcinogenic activities and applied as mixtures to mouse skin. Group A contained all of the 19 PAHs, group B seven PAHs for which there is sufficient evidence for carcinogenicity and group C 12 PAHs with only limited or inadequate evidence of carcinogenicity in experimental animals. 32P-Labelled DNA adducts formed by coal tar were resolved on TLC into a pattern of three discrete spots (2, 4 and 6) and four areas of diffuse radioactivity (1, 3, 5 and 7). By comparison of the pattern of adducts formed by coal tar with those formed by the synthetic mixtures it appeared that PAHs in group B formed coal tar-DNA adduct spots 4 and 6, and that adduct spot 2 was formed by PAHs in group C. Attempts to identify those PAHs responsible for the formation of coal tar-DNA adducts 4 and 6 were made by comparing the chromatographic mobilities of 32P-labelled coal tar-derived DNA adducts formed in mouse skin, using TLC and HPLC, with those formed by PAHs in group B. As benzo[ghi]perylene (B[ghi]P), a component of group C, has been demonstrated to exhibit significant DNA binding ability previously, the chromatographic mobility of coal tar-DNA adduct spot 2 was compared to that of the major DNA adducts formed by B[ghi]P in vivo and in vitro. It appeared that coal tar adduct spot 2 was the major adduct formed by B[ghi]P in vitro and that benzo[a]pyrene, benzo[b]fluoranthene, benzo [j]fluoranthene and benzo[k]fluoranthene contributed to the formation of adduct spot 6. None of the PAHs examined appeared to be responsible for the formation of adduct spot 4.

Animals↗
PubMed1993

The absence of cumulative bone marrow toxicity in patients with recurrent adenocarcinoma of the ovary receiving dose-intense taxol and granulocyte colony stimulating factor.

Forty-eight patients with recurrent adenocarcinoma of the ovary were treated with taxol and granulocyte colony stimulating factor (G-CSF), with a target taxol dose intensity of 250 mg/m2 every 3 weeks (83.3 mg/m2/week). We have assessed the patterns of granulocyte and platelet toxicity seen in this cohort. Individual patients received up to nine cycles of therapy. Criteria for entry onto protocol included good end organ function, good performance status and the absence of substantial co-morbid disease. Mean taxol dose intensity was 79.0 mg/m2/week for the whole cohort and did not diminish with increased duration of therapy. Granulocytopenia and thrombocytopenia were well controlled, with the average duration of platelet and neutropenic nadirs being less than 1 day for all cycles. There was no evidence of cumulative toxicity for granulocytes nor platelets, for up to eight cycles of therapy. We conclude that taxol, when given with G-CSF support, can be safely administered in a dose-intense fashion for multiple cycles of therapy, without cumulative bone marrow toxicity.

Adenocarcinoma↗
PubMed1993

Construction of chimeric proteins from the sigma N-associated transcriptional activators VnfA and AnfA of Azotobacter vinelandii shows that the determinants of promoter specificity lie outside the 'recognition' helix of the HTH motif in the C-terminal domain.

Functional chimeras have been generated from the transcriptional activators VnfA and AnfA, which control expression of the alternative nitrogenases in Azotobacter vinelandii. The activation profiles of the native and chimeric proteins have been determined using lacZ fusions to A. vinelandii anf and vnf promoters in Klebsiella pneumoniae. Replacing the C-terminal domain of AnfA with that of VnfA gives a protein with the promoter specificity of VnfA, confirming that the C-terminal domain contains the determinants of promoter specificity. However, substituting the VnfA sequence from the turn in the helix-turn-helix motif to the C-terminus does not alter the promoter specificity of AnfA. These changes in promoter specificity were reflected in changes in affinity for a VnfA-binding site, as measured by an in vivo repression assay using a lacZ fusion to a synthetic promoter. This supports the assumption that promoter recognition is determined by activator binding to enhancer--like sequences, and shows that the principal determinants of specific DNA-binding lie outside the 'recognition' helix. This may be a general feature of transcriptional activators dependent on sigma N (sigma 54). The chimera with the promoter specificity of VnfA retained the dependence on nitrogenase Fe protein characteristic of AnfA, indicating that this property is not related to particular promoter sequences, but is a function of the central or N-terminal domains of AnfA.

Amino Acid Sequence↗
PubMed1993

Mitral valve replacement for an annular submitral aneurysm of the left ventricle.

Successful surgical repair of an annular submitral aneurysm of the left ventricle in two patients is described. In both cases the diagnosis was made at surgery and they were treated successfully by transatrial closure of the aneurysm with Teflon felted sutures and mitral valve replacement. This is the first report of the use of mitral valve replacement for this condition.

Adult↗
PubMed1993

Comparison of total DNA adduct levels induced in mouse tissues and human skin by mainstream and sidestream cigarette smoke condensates.

Cigarette smoke condensates (CSCs) of both mainstream (MS) and sidestream (SS) smoke were used to treat mice topically in equivalent amounts. Human skin maintained in short-term culture was also treated with the condensates. DNA adducts, induced by the CSCs and detected by the nuclease P1 method of 32P-postlabelling, were quantified in a number of murine tissues and in the human skin DNA. In the five mouse tissues studied both MS-CSC and SS-CSC produced characteristic diagonal radioactive zones on TLC, indicative of the formation of multiple DNA adducts. In three tissues (skin, lung and kidney), SS-CSC induced greater total adduct levels than MS-CSC (statistically significant in skin and kidney, p < 0.05). However, greater adduct levels induced by MS-CSC were recorded for heart and bladder DNA (not statistically significant). Similar results to those found in mouse skin were obtained with human skin; SS-CSC induced a approximately 2-fold greater level of DNA adducts than MS-CSC (p < 0.05). Incubation of DNA directly with condensates in vitro demonstrated that DNA adducts could be formed without an exogenous metabolizing system. This direct interaction of condensates with DNA occurred at similar levels for both MS- and SS-CSC, although inclusion of an oxygen radical-generating system enhanced the SS-CSC binding to a greater extent than that of the MS-CSC.

Animals↗
PubMed1993

Isolation of Arcobacter butzleri from a drinking water reservoir in eastern Germany.

Microaerophilic "campylobacter-like organisms" (CLO) were isolated from a drinking water reservoir in Germany during a period of some months. The strains were characterized by biotyping (API Campy), serotyping and SDS-Disc-gelelectrophoresis as Arcobacter butzleri. Now this facultative humanpathogen species was first described in Germany. With respect to the drinking water treatment, the hygienic importance of the findings is given.

Bacterial Proteins↗
PubMed1993

Characterization of viable but nonculturable stage of C. coli, characterized with respect to electron microscopic findings, whole cell protein and lipooligosaccharide (LOS) patterns.

Campylobacter coli CK 205, isolated from swine feces, was examined for changes in cell morphology, protein and lipooligosaccharide (LOS) patterns during starvation-survival experiments. Bottles filled with sterile filtered A. dest. were seeded with campylobacters and incubated at 4 degrees C and 37 degrees C. Transition to the nonculturable stage occurred within 48 hours (37 degrees C) and 2 weeks (4 degrees C), respectively. In contrast to the culturability the electrophoretic studies showed no changes in whole cell protein or LOS patterns. The electron microscopic pictures revealed spiral and coccoid forms, partly with a slightly enlarged periplasmatic space or budding of the membrane. Totally intact non culturable spiral or coccoid forms might be regarded as dormancy forms that cannot be detected by conventional microbiological methods in water examination.

Animals↗
PubMed1992

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers.

In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin.

Animals↗
PubMed1992

DNA adduct formation in mice following treatment with used engine oil and identification of some of the major adducts by 32P-postlabelling.

Used engine oil from a petrol-powered vehicle was fractionated by column chromatography into seven parts for which the major polycyclic aromatic hydrocarbon (PAH) components were determined by GC. Topical treatment of mice with the fractions and 32P-postlabelling of the skin DNA resulted in the detection of multiple adduct spots on TLC for some, but not all, of the fractions. The majority of the DNA binding capacity of the used engine oil was possessed by the first three fractions, (equivalent to 25, 15 and 14.5%, respectively) of the adduct forming ability of the unfractionated oil. The chromatographic mobilities of the adduct spots induced by these fractions were compared to those produced by unfractionated used engine oil. In addition, mice were also treated topically with reference PAHs, either singly or as mixtures, dissolved in unused oil at the concentrations at which they were present in the used oil. Comparisons were made between the chromatographic mobilities of the adducts formed in mouse skin DNA by synthetic mixtures with those formed by the used oil. From these data, some of the major adducts produced by treatment with used engine oil are suggested to be formed by reactive metabolites of benzo[b]naphtho[1,2-d]thiophene, benzo[c]phenanthrene, benzo[g,h,i]fluoranthene, chrysene, benzo[a]pyrene and benzo[g,h,i]perylene.

Animals↗