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Biomedical subjects

J Jacob

Publications and source records attributed to J Jacob.

At least 127 records · Page 7Linked to original sources

Dependence of photosynthesis of sunflower and maize leaves on phosphate supply, ribulose-1,5-bisphosphate carboxylase/oxygenase activity, and ribulose-1,5-bisphosphate pool size.

Sunflower (Helianthus annuus L. cv Asmer) and maize (Zea mays L. cv Eta) plants were grown under controlled environmental conditions with a nutrient solution containing 0, 0.5, or 10 millimolar inorganic phosphate. Phosphate-deficient leaves had lower photosynthetic rates at ambient and saturating CO(2) and much smaller carboxylation efficiencies than those of plants grown with ample phosphate. In addition, phosphate-deficient leaves contained smaller quantities of total soluble proteins and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) per unit area, although the relative proportions of these components remained unchanged. The specific activity of Rubisco (estimated in the crude extracts of leaves) was significantly reduced by phosphate deficiency in sunflower but not in maize. Thus, there was a strong dependence of carboxylation efficiency and CO(2)-saturated photosynthetic rate on Rubisco activity only in sunflower. Phosphate deficiency decreased the 3-phosphoglycerate and ribulose-1,5-bisphosphate (RuBP) contents of the leaf in both species. The ratio of 3-phosphoglycerate to RuBP decreased in sunflower but increased in maize with phosphate deficiency. The calculated concentrations of RuBP and RuBP-binding sites in the chloroplast stroma decreased markedly with phosphate deficiency. The ratio of the stromal concentration of RuBP to that of RuBP-binding sites decreased in sunflower but was not affected in maize with phosphate deficiency. We suggest that a decrease in this ratio made the RuBP-binding sites more vulnerable to blockage or inactivation by tight-binding metabolites/inhibitors, causing a decrease in the initial specific activity of Rubisco in the crude extract from phosphate-deficient sunflower leaves. However, the decrease in Rubisco specific activity was much less than the decrease in the RuBP content in the leaf and its concentration in the stroma. A large ratio of RuBP to RuBP-binding sites may have maintained the Rubisco-specific activity in phosphate-deficient maize leaves. We conclude that the effect of phosphate deficiency is more on RuBP regeneration than on Rubisco activity in both sunflower and maize.

Journal Article↗

Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer.

PURPOSE: To increase the taxol dose beyond the current standard dose intensity of 175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND METHODS: Fifteen patients who had platinum-refractory or recurrent advanced-stage ovarian cancer were treated with taxol in a phase I trial and were given granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of 170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily subcutaneous injection that started 24 hours after the completion of the taxol infusion. RESULTS: Four patients required either taxol dose reduction or delay. The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at 300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove sensory disturbance that primarily affected proprioception, and was associated with objective changes on nerve conduction studies in affected individuals. Mucositis was rarely observed. Substantial myelosuppression was observed, but was not dose-limiting. Five of 14 assessable patients experienced an objective response to therapy, with another five individuals who experienced a 30% to 45% reduction in tumor mass. CONCLUSION: Taxol can be safely administered in doses up to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose intensification.

Adult↗

[The occurrence of Campylobacter in a mountain brook].

The mountain river showed fecal water pollution at all sample sites studied. The arithmetic mean values of total coliforms ranged between 28 and 196/ml. Campylobacters were isolated from all sample sites studied, with a maximum value of 1,100 Campylobacter/100 ml river water. The MCCD-medium resulted in significantly higher isolation rates of Campylobacter from water samples than the VTPRC-medium compared. Colony counts, total coliforms and Campylobacter showed numerical relations of 3831:100:1 respectively.

Campylobacter↗

[The occurrence of aeromonads in a drinking water supply system].

This study concerns with the occurrence of aeromonads, coliforms and colony counts in a drinking water supply. Aeromonas contents were detected in the range of 15.0 to greater than 2,400/100 ml in the raw water samples of the man made lake. After the drinking water treatment process including fast sand filtration and chlorination aeromonads indicated in comparison to total coliforms and colony counts early and significant an after-growth of maximal 240 aeromonads/100 ml in the peripheric drinking water supply. Drinking water samples characterized by a higher water temperature resulted in the highest contents of aeromonads. The Aeromonas-Species Aeromonas sobria and Aeromonas hydrophila were isolated most frequently with 56.9 and 37.4 percent, respectively. The role of aeromonads as an indicator of after-growth in drinking water supplies is discussed.

Aeromonas↗

Intraclonal generation of antibody mutants in germinal centres.

The generation and selection of somatic antibody mutants are key elements of acquired immunity, essential for the affinity maturation of antibody responses dependent on T cells. The mutants are generated through a mechanism that introduces point mutations at high rate into rearranged variable (V) region genes in the course of cell proliferation. Their appearance coincides with the generation of germinal centres, which are characterized by oligoclonal B-cell proliferation and have been suggested to be the microenvironment in which antibody mutants are generated. We report here direct evidence for this hypothesis. Rearranged V-region genes were amplified from the genomic DNA of cells picked from individual germinal centres. The sequence analysis of these genes revealed that most represent cells of distinct B-cell clones which expanded locally, generating somatic antibody mutants at high rate. By contrast, antigen-induced proliferation of B cells at another site, periarteriolar lymphocyte sheath-associated foci, was not associated with somatic hypermutation.

Amino Acid Sequence↗

Trusts in the ballot box.

The general election campaign will arouse yet more furious debate between Labour and the Conservatives over whether or not the NHS is being privatised. Joe Jacob examines the statutes to show that both sides are likely to be right--and wrong.

Politics↗

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations.

After primary immunization with an immunogenic conjugate of (4-hydroxy-3-nitrophenyl)acetyl, two anatomically and phenotypically distinct populations of antibody-forming cells arise in the spleen. As early as 2 d after immunization, foci of antigen-binding B cells are observed along the periphery of the periarteriolar lymphoid sheaths. These foci expand, occupying as much as 1% of the splenic volume by day 8 of the response. Later, foci grow smaller and are virtually absent from the spleen by day 14. A second responding population, germinal center B cells, appear on day 8-10 and persist at least until day 16 post-immunization. Individual foci and germinal centers represent discrete pauciclonal populations that apparently undergo somatic evolution in the course of the primary response. We suggest that foci may represent regions of predominantly interclonal competition for antigen among unmutated B cells, while germinal centers are sites of intraclonal clonal competition between mutated sister lymphocytes.

Animals↗

Fluorescence response in chlortetracycline-loaded neutrophils measures release of Ca2+ from intracellular membrane enclosed storage sites.

Chlortetracycline complexes with di- and trivalent cations resulting in an enhancement of its fluorescence emission intensity. Rabbit peritoneal neutrophils loaded with chlortetracycline gave a fluorescence response, even in the absence of extracellular Ca2+ and Mg2+, by a decrease in fluorescence intensity. The shift in the fluorescence emission maximum to lower wavelengths after the response suggested the response to be due to Ca2+ and not Mg2+ flux. The response was elicited by three mechanisms--a receptor-mediated mechanism by the chemotactic peptide, an ionophore-mediated one by lasalocid, and a detergent-mediated response by digitonin. These observations indicated that the response was due to transport of calcium across membranes in the intracellular compartments and may be physiologically significant. Whereas extracellular Ca2+ did not significantly affect the chemotactic peptide and lasalocid-mediated responses, Ca2+ inhibited the digitonin-mediated responses in a dose-dependent manner possibly due to extracellular Ca2+ flooding the cytosol through the digitonin-permeabilized plasma membrane and equilibrating the Ca2+ gradient across the intracellular membranes. The data collectively indicate that the fluorescence response is due to release of Ca2+ across intracellular membranes from a Ca2+ storage site into the cytosol.

Animals↗

Rat liver microsomal ring- and S-oxidation of thiaarenes with central or peripheral thiophene rings.

The metabolism of the following thiaarenes has been investigated using liver microsomes of untreated, phenobarbital-, AroclorR- and 5,6-benzoflavone-pretreated rats: dibenzothiophene, naphtho[2,1-b]thiophene, benzo[b]naphtho[2,1-b]thiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho-[2,3-d] thiophene, phenanthrol[1,2-b]thiophene, phenanthrol[4,5-bcd] thiophene, triphenyleno[1,12-bcd]-thiophene and dinaphtho[2,1-b:1',2'-d]thiophene. Thiaarenes with a central thiophene ring preferentially undergo S-oxidation and are converted into sulfoxides and sulfones, whereas those with a peripheral thiophene ring are oxidized at the carbocyclic skeleton resulting in the formation of phenols, dihydrodiols and triols. Sulfone formation seems to be inducible by phenobarbital but only little or not by 5,6-benzoflavone treatment. In most cases 5,6-benzoflavone and AroclorR treatment enhanced the rates of ring oxidation.

Animals↗

[Acute corticosteroid myopathy in patient with asthma].

A patient, treated by mechanical ventilation with pancuronium or atracurium and with intravenously administered corticosteroid for status asthmaticus, presented with rhabdomyolysis (severe amyotrophy and marked of creatine kinase activity) and acute flacid and areflexic quadriplegia, involving the proximal and distal muscles but sparing the cephalic musculature. After review of the investigations (biochemistry, electromyogram, muscle biopsy), the diagnostic of acute corticosteroid myopathy following status asthmaticus was suggested, and a pancuronium neuromuscular complication or a critically ill polyneuropathy excluded. The non-inflammatory rhabdomyolysis concerned all the fiber types. Predominantly distal weakness resolved six months after the insult, in spite of the laboratory recurrence of the rhabdomyolysis at the time of a new status asthmaticus briefly treated with corticosteroid.

Acute Disease↗

Measures of renal function in patients with cisplatin-related chronic renal disease.

Twenty-seven patients with advanced stage refractory ovarian cancer were studied to determine if chronic stable cisplatin-related renal dysfunction was present. Medical histories were examined to determine the types of therapy previously received as well as the total previous platinum doses received that ranged from 200 to 2,100 mg/m2. Standard assessments of renal function were made prior to administering current chemotherapy or immunotherapy to the patient, which included 24-hour creatinine clearance, serum creatinine, and blood urea nitrogen (BUN). For patients with a 24-hour creatinine clearance of less than 60 mL/minute, serum creatinine was highly variable (range: 0.9 to 2.0 mg/dL) and was not related to the degree of diminution in the 24-hour creatinine clearance value. Conversely, for patients with a serum creatinine of less than 1.5, the 24-hour creatinine clearance values varied by almost three-fold, ranging between 46 and 120 mL/minute. Two patients with serum creatinines of less than 1 had creatinine clearances of less than 50 mL per minute. Similarly, BUN measurements did not correlate with 24-hour creatinine clearance values, and the 24-hour creatinine clearance value was not related to the total cumulative platinum dose. We conclude that patients who receive substantive doses of cisplatin may experience chronic stable cisplatin-related renal dysfunction and that serum creatinine cannot be relied on to assess the degree of renal compromise. In such patients, we recommended that the 24-hour creatinine clearance value should be used when medical management is influenced by renal function.

Adult↗

Confidentiality: a survey in a research hospital.

Despite the many justifications for protecting patient confidentiality, we recognize that confidentiality cannot be absolute. Our world of automated information and easy access and storage poses many threats to confidentiality. This paper has described a survey conducted at the NIH Clinical Center to assess the knowledge, attitudes, and behaviors of clinical physicians and nurses about confidentiality of patient information. The survey findings demonstrate the need for reminders and increased awareness about confidentiality in our setting. Most of the survey respondents had a good knowledge of what was expected of them, and they believed that confidentiality was important and maintaining it was their responsibility. Of interest was that in several simulated clinical situations, there was a discrepancy between what respondents indicated they should do and what they thought they would do. The biggest discrepancies appeared in situations that involved overhearing a patient conversation on the elevator, approaching an unfamiliar person who is reading a medical record in the nurses' station, and answering a patient's inquiry about the status of another patient. The findings support the speculation that this difference may be attributed to discomfort or decreased awareness, and not necessarily to lack of knowledge. Results indicate that policies and administrative expectations should be frequently communicated and enforced, and that educational programs that address issues of confidentiality should be provided. The results of this survey have been influential in guiding educational strategies and administrative activities at the clinical center. The clinical center initiated a confidentiality awareness campaign, displaying a new poster every three months in strategic locations and distributing other tangible reminders (such as pens, magnets, and buttons) containing the same confidentiality message.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel↗

Characterization of thermophilic campylobacters originated from a high-rate sewage treatment plant.

Campylobacter strains isolated during a one-year study from a municipal waste water treatment plant have been characterized. The study shows a considerable release of Campylobacter strains into the receiving linked river system. Campylobacters isolated here, are very similar to isolates originating from enteritic cases. In contrast to other reports we conclude that the strains released from the sewage treatment plant into the environment represent a potential risk for public health.

Bacterial Proteins↗

[The occurrence and survival of Campylobacter in sewage sludge].

Campylobacter was found only in raw sewage sludge samples of the high-rate municipal sewage treatment plant studied. Campylobacters were isolated from 28.6% of the sewage sludge samples of grit tank and primary settling tank. 40% of the settled activated sludge samples contained Campylobacter. Campylobacter was never found in digested sludge of a mean sludge age of more than 90 days. The survival times of Campylobacter in sewage sludge samples ranged between some hours and 10 days. Therefore a low risk of the spread of Campylobacter in the environment due to agricultural application of digested sewage sludge is assumed.

Campylobacter↗

Environmental aspects of Campylobacter infections.

Epidemiological data indicate high incidence of campylobacteriosis. Improperly prepared poultry-products, unpasteurized milk as well as non-chlorinated drinking water were shown to be the main vehicles of Campylobacter transmission to man. There is a lack of knowledge concerning the role of various environments in transmission of Campylobacter. The review summarizes the present knowledge about occurrence and survival of Campylobacters in various environments (sewage, sludge, surface water, drinking water). In conclusion risk assessment for public health is discussed.

Animals↗

Effect of doxorubicin on local recurrence following marginal resection in the MGH-OGS murine model.

Despite the fact that preoperative chemotherapy causes substantial necrosis in the primary osteosarcoma tumor, most authorities recommend resecting these lesions with a wide margin of normal tissue to avoid local recurrence. This study evaluated the effect of systemic chemotherapy (doxorubicin) on tumor growth and histology in the MGH-OGS transplantable murine model and examined whether this drug prevents local recurrence after resection of the tumor with positive microscopic margins. The results indicate that doxorubicin caused prolonged cessation of tumor growth, produced substantial necrosis within the lesion, and decreased the risk of local relapse following marginal surgery. The drug effect was dose-dependent and drug efficacy in preventing local relapse was maximal with administration prior to or at the time of surgery.

Animals↗

Analysis of the polycyclic aromatic hydrocarbon content of petrol and diesel engine lubricating oils and determination of DNA adducts in topically treated mice by 32P-postlabelling.

Engine lubricating oils are known to accumulate carcinogenic polycyclic aromatic hydrocarbons (PAHs) during engine running. Oils from nine petrol-powered and 11 diesel-powered vehicles, in addition to samples of unused oil, were analysed for PAH content and ability to form DNA adducts when applied topically to mouse skin. The levels of 19 PAHs, determined by GC, were in total, approximately 22 times higher in used oils from petrol engines than in oils from diesel engines. Male Parkes mice were treated with 50 microliters of oil daily for 4 days before they were killed and DNA isolated from skin and lung tissue. DNA samples were analysed by nuclease P1-enhanced 32P-postlabelling. Used oils from both diesel and petrol engines showed several adduct spots on PEI-cellulose plates at total adduct levels of up to 0.57 fmol/microgram DNA [approximately 60 times greater than in experiments with samples of unused oil in which adduct levels (0.01-0.02 fmol adducts/microgram DNA) were close to the limit of detection]. Higher adduct levels were generally formed by petrol engine oils than by diesel engine oils. Lung DNA contained similar total adduct levels to those in skin although the adduct maps were less complex. Total adduct levels correlated with extent of oil use in the engine, the total PAH concentration in oils and with the concentrations of certain individual PAHs present in the oils. An adduct spot that co-eluted with that of the major benzo[a]pyrene-DNA adduct accounted for 9-26% of the total adducts in skin DNA, and approximately 8% of the adducts in lung DNA, of mice treated with petrol engine oils. A major, and as yet unidentified, adduct spot comprised up to 30% of the total adducts in skin DNA, and up to 89% of the total adducts in lung DNA, of these animals.

Administration, Topical↗

Mouse paw oedema induced by Habu snake (Trimeresurus flavoviridis) venom: inhibition by morphine, naloxone and methylnaloxone alone or in combinations.

The oedema produced in the mouse by intraplantar injection of the venom of Trimeresurus flavoviridis was inhibited by morphine (Mo) and by naloxone (Nx); the action of Mo increased with the dose, whereas that of Nx first progressed and thereafter regressed with the dose; very small doses of Nx antagonized Mo. Methylnaloxone (MeNx), a quaternary ammonium derivative of Nx was much less effective than Nx by the subcutaneous route but almost as effective by the intraplantar route. Peripheral opioidergic receptors are thus likely to be involved. Very high doses of Mo acted an synergistically with an optimal dose of EDTA or zymosan; complex interactions occurred between lower doses of Mo or Nx and EDTA or zymosan.

Animals↗