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Biomedical subjects

R May

Publications and source records attributed to R May.

At least 37 records · Page 2Linked to original sources

Characterization of two epiphytic bacteria from soybean leaves with antagonistic activities against Pseudomonas syringae pv. glycinea.

The strains 48b/90 and 22d/93 are naturally occurring ephiphytes which were isolated from soybean leaves. On the basis of pheno- and genotypic characteristics 48b/90 was identified as Erwinia herbicola and 22d/93 as Pseudomonas syringae. These two isolates produced biological active substances against different indicator organisms. The E. herbicola strain showed clear antagonistic properties against Escherichia coli and Pseudomonas syringae pv. glycinea, but not against Geotrichum candidum. 22d/93 was active against P. glycinea and G. candidum, but not against E. coli. Strain 48b/90 produced at least two different inhibitors: an antibiotic substance and an inhibitor of the alginate synthesis. Strain 22d/93 produced at least three different compounds inhibitory to P. glycinea and one to G. candidum. Their activities against the bacterial blight pathogen, P. glycinea, can be observed in planta, too. Under the influences of the antagonists the pathogen multiplied at lower rates and to lower stationary phase population levels. The development of bacterial blight symptoms was suppressed.

Anti-Bacterial Agents↗

Assessing dissimulation among Social Security disability income claimants.

Social Security disability income programs have been tested by increasingly politicized concerns regarding widespread fraud among claimants. This study was an initial investigation of malingering among claimants in Los Angeles seeking disability income on psychological grounds. After a review of 100 disability income applications, a population-appropriate instrument was developed from established psychometric indices of malingering. The Composite Disability Malingering Index was completed by 167 disability claimants (possible malingerers), a sex, age and IQ cognate group of 63 psychologically disabled individuals without incentive to malinger (disabled nonmalingerers), and 45 disability examiners with instructions to malinger (instructed malingerers). The mean score of instructed malingerers and the score at the 95th percentile of the disabled nonmalingerers converged, indicating 8 as the critical score. This cutting score found 32 (19%) of disability claimants to be malingering. Self-reported substance abuse history was the only participant variable that significantly predicted higher malingering scores.

Adult↗

Polyarteritis nodosa with pulmonary vasculitis.

Although early postmortem series reported pulmonary involvement as a relatively common manifestation of polyarteritis nodosa (PAN), using the modern classification of PAN pulmonary involvement is very uncommon. A 62-yr-old male with well-documented classic PAN was found to have an arteritis of medium-sized muscular pulmonary arteries. The patient subsequently demonstrated a complete response to treatment. Of the few reported cases of PAN with pulmonary manifestations, the majority are autopsy series and the vascular lesion involves the bronchial arteries. There are no case reports of patients with pulmonary involvement of PAN who responded successfully to treatment. This case is the first description of a premortum diagnosis of pulmonary arteritis in PAN in which the patient had a response to treatment.

Alkylating Agents↗

The effect of antimicrobial therapy on testicular aspirate flow cytometry.

Many antibiotics have been shown to have adverse effects on spermatogenesis. Deoxyribonucleic acid (DNA) flow cytometry of testicular aspirate has been shown to be an effective method of quantitatively evaluating testicular function. To assess this problem, DNA flow cytometry of testicular aspirate was performed on 8 groups of rats, each of which received antibiotics via daily gavage for 10 days. Aspirations were performed on days 0, 11 and 56. Data thus obtained were analyzed using a two-way ANOVA with repeated measures. Antibiotics studies included ciprofloxacin 15 mg./kg./day, sulfamethoxazole (SMX) 20 mg./kg./day (with trimethoprim (TMP) 4 mg./kg./day), nitrofurantoin 7 mg./kg./day, ofloxacin 10 mg./kg./day, lomefloxacin 6 mg./kg./day, doxycycline 3 mg./kg./day and norfloxacin 10 mg./kg./day. One group received the same SMX/TMP dose, together with folate 0.014 mg./kg./day. A statistically significant change in aspirate content on day 11 as compared with baseline existed in groups receiving TMP/SMX (p = 0.00025), nitrofurantoin (p = 0.0000043), ofloxacin (p = 0.000075) and doxycycline (p = 4.89 X 10(-9). Control rats and the group receiving TMP/SMX with folate showed no significant change. On day 56 the abnormality persisted in groups TMP/SMX (p = 0.042), nitrofurantoin (p = 0.001), ofloxacin (p = 0.036) and doxycycline (p = 0.003). Controls and groups receiving ciprofloxacin, norfloxacin and lomefloxacin continued to show no statistically significant difference from baseline on day 56. These data suggest that SMX/TMP, nitrofurantoin, ofloxacin and doxycycline significantly alter spermatogenesis. Ciprofloxacin, norfloxacin and lomefloxacin had no apparent effect on spermatogenesis as measured by DNA flow cytometry.

Animals↗

Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes.

Perineurial cells are specialized connective tissue cells that form a barrier between endoneurium and epineurium in normal nerves. In the present study, the formation of the perineurium after transection of rat sciatic nerves was investigated. The cord bridging the gap between proximal and distal stumps through silicone tubes was studied 3, 7, 12, 18, and 21 days after surgery using electron microscopy and antibodies against epithelial membrane antigen (EMA), a marker for perineurial cells that has thus far not been applied to the study of differentiating cells in nerve tubulation systems. Initially, a thin cord consisting of fibrin bridged the gap between the stumps. At 7 days, longitudinal cells had migrated from both stumps toward the center of the tubes on the surface of the fibrin cord. These cells were immunoreactive with anti-EMA. At 12 days, ultrastructural features of perineurial cells (desmosomes, tight junctions, actin filaments with dense bodies, tonofilaments) were prominent in these cells. Subsequently, the gap was bridged through the perineurial tube by endothelial cells, pericytes, fibroblasts, Schwann cells, and axons. At 21 days, a single large nerve fascicle ensheathed by a mature perineurium was found between the stumps. Thus, the first cells to connect proximal and distal stumps in the investigated nerve regeneration silicon chamber system are perineurial cells. Through the tube formed by these cells, blood vessels and nerve fibers bridge the gap. Therefore, establishment of a perineurial connection between nerve stumps appears to be important in the sequence of events during nerve regeneration.

Animals↗

A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Adult↗

Large-scale preparation of fully deuterated cell components. Ribosomes from Escherichia coli with high biological activity.

Some applications of NMR and of neutron scattering require fully deuterated biological material which should be highly active and available in large quantities. These requirements are hardly compatible since full deuteration is achieved easily only if cells are grown in minimal media. This condition used in standard batch fermentation results in both low yields and reduced activities of the biological mass. Here we report a method which combines the apparently incompatible requirements taking advantage of a recent observation according to which the appearance of growth inhibiting extracellular products could be prevented. The method was applied for growing Escherichia coli cells, strain MRE600rif (resistance against high doses of rifampicin is used as selection marker) on partially deuterated media (76% and 84% D2O) with glucose as carbon source and on deuterated acetate and succinate with 100% D2O when full deuteration was to be achieved. The essential point for preserving the log-phase character of the cells is that the cultivation is carried out at substrate limiting conditions thus keeping the growth rate at low levels (for glucose the growth rate, mu < or = 0.35 h-1, for acetate/succinate mu < or = 0.1 h-1) which avoids the accumulation of the substrate or of by-products in the medium. Our data suggest that acetate is a main extracellular component for accompanying or triggering the transition from logarithmic growth to stationary phase of E. coli cells cultivated on glucose as carbon source. The cells were first grown in fed-batch to high cell densities (above 50 g wet cells/l) under conditions of substrate limitations. A steady-flow fermentation followed keeping the growth rate at about mu of 0.1 h-1. Cells were harvested in kg quantities, the extracted ribosomes showed a normal complement of proteins, contained intact rRNA and were fully active. The ribosomal protein and rRNA fractions could be efficiently reconstituted to highly active particles. In the case of full deuteration a matching point of 120% (tentative D2O scale) was achieved. The reported method facilitates the preparation of deuterated biological material for applications in NMR and neutron scattering analysis.

Acetates↗

Juvenile hereditary polyglucosan body disease with complete branching enzyme deficiency (type IV glycogenosis).

Polyglucosan body diseases in adults, contrary to infantile cases (Andersen's disease or type IV glycogenosis or amylopectinosis), are usually not associated with a significant deficiency of the branching enzyme (= amylo-1,4-1,6 transglucosidase). We, therefore, report on a 19-year-old male with complete branching enzyme deficiency presenting with severe myopathy, dilative cardiomyopathy, heart failure, dysmorphic features, and subclinical neuropathy. His 14-year-old brother had similar symptoms and was erroneously classified by a previous muscle biopsy as having central core disease but could later be identified as also having polyglucosan body myopathy. The skeletal muscle, endomyocardiac, and sural nerve biopsies as well as the autopsy revealed extraordinarily severe deposits of polyglucosan bodies not only in striated and smooth muscle fibers, but also in histiocytes, fibroblasts, perineurial cells, axons and astrocytes. Occasional paracrystalline mitochondrial inclusions were also noted. Thus, this patient represents to our knowledge the first juvenile, familial case of polyglucosan body disease with total branching enzyme deficiency and extensive polyglucosan body storage.

1,4-alpha-Glucan Branching Enzyme↗

Perineurial cells are the first to traverse gaps of peripheral nerves in silicone tubes.

Silicon tubes were used to study the outgrowth and differentiation of the perineurium around the cord bridging the gap between the proximal and distal stumps of the transected sciatic nerve of rats. The sequence of events was investigated at time intervals 3, 7, 12, 18, and 21 days after surgery. Although similar tubulation systems have been used to investigate various aspects of peripheral nerve fibre regeneration, the present study shows for the first time with electron microscopic and immunocytochemical methods that a primitive perineurium bridges the gap as the initial cellular element. This perineurium develops from outgrowing fibroblasts as early as 7 days post surgery, forming a tube which is used as a guiding structure for subsequent cellular elements. The proximal and distal perineurial tubes join between 12 and 18 days after surgery thus representing the first connection between the proximal and distal nerve stumps. Blood vessels, Schwann cells, and axons appear to follow in this sequence.

Animals↗

Buprenorphine versus morphine for patient-controlled analgesia after cholecystectomy.

Buprenorphine is an opioid agonist-antagonist that has emerged as an option for postoperative analgesia. We compared the postoperative hospital course of patients undergoing open cholecystectomy who received buprenorphine hydrochloride with those who received morphine sulfate. Patients in both groups administered the analgesic using a patient-controlled analgesia infusion device. Comparison of the two groups demonstrated no difference with respect to clinical indicators of intestinal motility, visual analog pain scores and hospitalization period. Postoperative nausea occurred more frequently in the buprenorphine group, but the difference was not significant. We concluded that the patient-controlled analgesia device is a valuable tool for comparing different analgesics. Both analgesics tested provide adequate analgesia with a similar postoperative course.

Adolescent↗

Domain structure of the human immunodeficiency virus reverse transcriptase.

The spatial arrangement of subunits p51 and p66 of the HIV-1 reverse transcriptase and the position of the RNase H containing domain, p15, have been determined by means of neutron small-angle scattering. The reverse transcriptase (p66/p51) is a flat molecule, which can be approximated by an ellipsoid with the half axes of 5.2 nm, 4.8 nm and 1.4 nm. The two subunits p51 and p66 having a centre-to-centre distance of 3.3 +/- 0.3 nm are attached at their flat sides, slightly shifted sideways. The p15 domain is located at the long axis of the ellipsoidal reverse transcriptase having a distance of 5.0 +/- 0.5 nm to the centre of the p51d domain, which is part of the p66 subunit, and a distance of 5.3 +/- 1.2 nm to the centre of the neighbouring p51s subunit.

Chromatography, Affinity↗

Structural dynamics of translating ribosomes.

We describe three groups of small angle neutron scattering (SANS) experiments with translating ribosomes: 1) regular protonated (normal abundance hydrogen) particles; 2) two isotopic hybrid particles which are reconstituted from one protonated and the other deuterated subunit; 3) four isotypic hybrid particles differing from each other by the extent of protein and RNA deuteration. Using the SANS contrast variation method the radii of gyration of protein and RNA components in both ribosomal subunits as well as the intersubunit distance in the pre- and post-translocation states were determined. The results obtained suggest the following model of the ribosome as a dynamic machine. The ribosome oscillates between two major conformers differing in geometrical dimensions. The 'active' (pulsating) part of the ribosome is the 30S subunit. We believe that the movement of its 'head' relative to the passive 50S subunit is the main mechanical act of translocation. The radius of gyration of the 30S subunit and the intersubunit distance change upon the movement. This is corroborated by neutron scattering data.

Bacterial Proteins↗

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phase I immunotoxin trial in patients with B-cell lymphoma.

Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.

Adult↗