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Biomedical subjects

B M Johnson

Publications and source records attributed to B M Johnson.

At least 19 recordsLinked to original sources
PubMed2004

In vitro activity of gemifloxacin and contemporary oral antimicrobial agents against 27247 Gram-positive and Gram-negative aerobic isolates: a global surveillance study.

This study was a multi-centre, multi-country surveillance of 27247 Gram-positive and Gram-negative isolates collected from 131 study centres in 44 countries from 1997 to 2000. MICs of gemifloxacin were compared with penicillin, amoxicillin-clavulanic acid, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulphamethoxazole, ciprofloxacin, grepafloxacin and levofloxacin by broth microdilution. Penicillin resistance in Streptococcus pneumoniae was extremely high in the Middle East (65.6%), Africa (64.0%) and Asia (60.4%) and lower in North America (40.3%), Europe (36.9%) and the South Pacific (31.8%). Macrolide resistance in S. pneumoniae was highest in Asia (51.7%) but varied widely between laboratories in Europe (26.0%), North America (21.6%), the Middle East (13.7%), the South Pacific (10.6%) and Africa (10.0%). All the study quinolones were highly active against penicillin-resistant and macrolide-resistant S. pneumoniae. Overall, gemifloxacin had the lowest MIC(90) at 0.06 mg/l with MICs 4-64-fold lower than ciprofloxacin, levofloxacin and grepafloxacin against S. pneumoniae. Gemifloxacin MICs were more potent than grepafloxacin > levoflaxacin > ciproflaxin against the Gram-positive aerobes and shared comparable Gram-negative activity with ciprofloxacin and levofloxacin.

Administration, Oral↗
PubMed2004

Determining incidence of extended spectrum beta-lactamase producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus in 38 centres from 17 countries: the PEARLS study 2001-2002.

The PEARLS study prospectively monitored selected nosocomial pathogens from 38 centres in 13 European, three Middle Eastern countries and South Africa during 2001-2002. Extended spectrum beta-lactamase (ESBL) production rates among Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. were 5.4% (142/2609), 18.2% (401/2,206) and 8.8% (204/2,328), respectively, for all study sites. The overall ESBL production rate for the combined Enterobacteriaceae was 10.5% (747/7,143), highest in Egypt, 38.5%, and Greece, 27.4%, and lowest in The Netherlands, 2.0%, and Germany, 2.6%. IEF, PCR and DNA sequencing determined 10.7% false positives among Enterobacter spp. when using NCCLS guidelines to screen for ESBL production. The prevalence of nosocomial methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium was 32.4% (294/908) and 8.7% (83/949), respectively. PEARLS provides baseline data against which prospective changes in resistant determinants and outcomes can be measured in this ongoing study.

Anti-Bacterial Agents↗
PubMed2001

Screening botanical extracts for quinoid metabolites.

Botanical dietary supplements represent a significant share of the growing market for alternative medicine in the USA, where current regulations do not require assessment of their safety. To help ensure the safety of such products, an in vitro assay using pulsed ultrafiltration and LC-MS-MS has been developed to screen botanical extracts for the formation of electrophilic and potentially toxic quinoid species upon bioactivation by hepatic cytochromes P450. Rat liver microsomes were trapped in a flow-through chamber by an ultrafiltration membrane, and samples containing botanical extracts, GSH and NADP(H), were flow-injected into the chamber. Botanical compounds that were metabolized to reactive intermediates formed stable GSH adducts mimicking a common in vivo detoxification pathway. If present in the ultrafiltrate, GSH conjugates were detected using LC-MS-MS with precursor ion scanning followed by additional characterization using product ion scanning and comparison to standard compounds. As expected, no GSH adducts of reactive metabolites were found in extracts of Trifolium pratense L. (red clover), which are under investigation as botanical dietary supplements for the management of menopause. However, extracts of Sassafras albidum (Nutt.) Nees (sassafras), Symphytum officinale L. (comfrey), and Rosmarinus officinalis L. (rosemary), all of which are known to contain compounds that are either carcinogenic or toxic to mammals, produced GSH adducts during this screening assay. Several compounds that formed GSH conjugates including novel metabolites of rosmarinic acid were identified using database searching and additional LC-MS-MS studies. This assay should be useful as a preliminary toxicity screen during the development of botanical dietary supplements. A positive test suggests that additional toxicological studies are warranted before human consumption of a botanical product.

Animals↗
PubMed2001

The impact of P-glycoprotein efflux on enterocyte residence time and enterocyte-based metabolism of verapamil.

P-glycoprotein (P-gp) can limit the intestinal permeability of a number of compounds and may therefore influence their exposure to metabolizing enzymes within the enterocyte (e.g. cytochrome P450 3A, CYP 3A). In this study, the intestinal metabolic profile of verapamil, the influence of P-gp anti-transport on the cellular residence time of verapamil, and the impact of this change in residence time on the extent of enterocyte-based metabolism have been investigated in-vitro, utilizing segments of rat jejunum and side-by-side diffusion chambers. Verapamil exhibited concentration-dependent P-gp efflux and CYP 3A metabolism. The P-gp efflux of verapamil (1 microM) increased the cellular residence time across the intestinal membrane (approximately 3-fold) in the mucosal to serosal (m to s) direction relative to serosal to mucosal (s to m), yielding significantly greater metabolism (approximately 2-fold), presumably as a result of the prolonged exposure to CYP 3A. Intestinal metabolism of verapamil generated not only norverapamil, but resulted also in the formation of an N-dealkylated product (D-617). Norverapamil and D-617 accumulated significantly in mucosal chambers, relative to serosal chambers, over the time course of the experiment. Based on these in-vitro data, it was apparent that P-gp efflux prolonged the cellular residence time of verapamil (m to s) and therefore increased the extent of intestinal metabolism, and also played a role in metabolite secretion from within the enterocyte.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Combined c-fos and 14C-2-deoxyglucose method to differentiate site-specific excitation from disinhibition: analysis of maternal behavior in the rat.

On the basis of evidence that 14C-2-deoxyglucose (2-DG) autoradiography indicates activity at axonal terminals, whereas c-fos immunocytochemistry indicates activity of neuronal cell bodies, we combined these techniques in adjacent histological brain sections to assess excitatory and disinhibitory synaptic relations in selected sites in female rats in which maternal behavior was elicited by natural parturition, sensitization (7- to 10-day cohabitation with foster pups), or hysterectomy. All individuals in these three groups expressed maternal behavior immediately before 2-DG injection. Controls were non-maternal virgins. Parturient and Hysterectomized groups: elevation (compared with controls) in both 2-DG and c-fos activity in medial preoptic area (MPOA) indicated an increase in its input and output activity, i.e., an excitatory interaction; the MPOA was previously shown to be critical for maternal behavior. Sensitized group: a decrease in 2-DG activity of vomeronasal nuclei (bed nucleus of the accessory olfactory tract, BAOT, and medial amygdala, ME, replicating our previous study) and an elevation in c-fos activity, jointly indicate disinhibition of these nuclei, that were previously shown to modulate pup-chemostimulation-induced sensitization. All other sites showed evidence of excitatory input-output relationships (i.e., joint increase in both 2-DG and c-fos activity), e.g., bed nucleus of the stria terminalis (BNST), lateral habenula (LHAB), central gray (CG), thalamus (THAL), septum (SEPT), and ventral tegmental area (VTA). The present study demonstrates the feasibility of measuring 2-DG and c-fos activity jointly in adjacent sections of the same brain, thereby providing evidence to distinguish between localized excitation and disinhibition.

Animals↗
PubMed1996

Antinociceptive action of vaginocervical stimulation in rat spinal cord: 2-DG analysis.

Using [14C] 2-deoxyglucose (2-DG) autoradiography with computerized densitometric analysis, unilateral foot pinch was found to significantly increase the relative optical density in laminae I and II of the ipsilateral, compared to the contralateral, spinal cord at lumbar 5 (L5). However, during vaginocervical mechanostimulation applied concurrently with the unilateral foot pinch, no comparable difference was observed. No response to foot pinch was observed in other laminae of the spinal cord at L5, and no effects comparable to the above were observed at L3. These findings indicate that vaginocervical mechanostimulation suppresses neural responses to noxious foot pinch stimulation selectively at the laminae I and II level of the spinal cord at L5, but not at L3.

Animals↗
PubMed1995

Brain 2-deoxyglucose levels related to maternal behavior-inducing stimuli in the rat.

Levels of [14C]2-deoxyglucose (2-DG), measured autoradiographically, in the medial preoptic area (MPOA), were higher during natural parturition with concurrent maternal behavior than in non-pregnant non-maternal controls, whereas levels in the vomeronasal system were lower in virgin rats made maternal by cohabitation with young than in control and parturient rats. Previous studies have shown that lesions of MPOA disrupt maternal behavior, whereas lesions of vomeronasal structures stimulate it, and that an increase in 2-DG levels is indicative of an increase in firing activity in neuron terminals. Consequently, the present findings suggest that maternal behavior can be induced by: (a) an increase in parturition-generated sensory stimulatory input to the MPOA in response to mechanostimulation of the birth canal, and (b) a separate chemosensory vomeronasal pathway whose activity is reduced cohabitation with young, thereby disinhibiting maternal behavior.

Animals↗
PubMed1993

The natural history of the anterior cruciate ligament-deficient knee. A review.

The ACL-deficient knee has been a management dilemma for many years and, to this day, no refutable plan exists for treatment of this injury. No true prospective study has been performed that evaluates all types of individuals at a variety of activity levels, and, in this day of apparently reliable methods of reconstructing the ACL, it is doubtful that one will occur. The ACL injury is no longer a mystery to the general public; it has received extensive publicity because of injuries of professional athletes and the successful reconstruction in many of these athletes. This article has not completely cleared up the issue of the future of an ACL-deficient knee. It has provided, however, convincing evidence that an active individual with a nonfunctional ACL is susceptible to meniscus injury (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). There is also the risk of more tears occurring with time. Bray and Dandy found in their follow-up of patients with ACL repairs that, if the pivot shift returned, these patients had a much higher incidence of meniscus tears. Many of these studies indicate that, if the meniscus cannot be repaired and requires partial meniscectomy or worse, the articular surface will deteriorate (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). Satku et al showed only 11% incidence of radiographic changes in patients with ACL-deficient knees with no evidence of meniscus tears compared with 100% in those having meniscectomy more than 5 years previously. Activity levels in general also change following this injury. This is probably the most difficult area to assess. Even though a substantial number of persons returned to their preinjury level of activity, it is not always possible to determine if they are playing with the same behavior and attitude. In other words, athletes who are involved in sports with cutting and jumping may modify the need for these activities and yet remain relatively competitive depending on their previous level of skill and the position they play. It has also been shown that many athletes return to their preinjury level initially but with time have significant increase in their symptoms and must modify their level of participation. More individuals limited their activities from the beginning than returned to their preinjury level (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication, 1990). Instability varies in these individuals and, as in Chick and Jackson's patients, those with mild instability (no rotatory instability) may do reasonably well.(ABSTRACT TRUNCATED AT 400 WORDS)

Anterior Cruciate Ligament↗
PubMed1988

Ultrastructural and paraphenylene studies of degeneration in the primate visual system: degenerative remnants persist for much longer than expected.

It is a widely held belief that the products of axonal degeneration in the CNS are transitory and are caused by metabolic and phagocytic processes. However, recent light microscopic examinations of human and primate brains using the paraphenylene diamine staining method (PPD), which stains degenerating axons, have confirmed that the products of degeneration persist for years in visual pathways. The routine utilization of the PPD method for delineating human visual pathways requires further confirmation of axonal degeneration. Optic nerves, optic tracts, and lateral geniculate nuclei were collected from human brains that had clinical documentation of optic nerve damage prior to death. Optic nerves, optic tracts, and lateral geniculate nuclei taken from the brains of cynomolgus monkeys that had undergone enucleation 3 months to 1 year prior to sacrifice were also examined. All tissue was processed for electron microscopy; ultrathin sections were cut for electron microscopy, and consecutive sections were cut for light microscopy. In all cases, the homology of the degenerated processes was confirmed between the light microscopic (PPD) and the electron microscopic sections. Such ultrastructural examination demonstrates that the products of axonal degeneration remain in the primate visual system longer than previously supposed.

Animals↗
PubMed1983

Immune response to a thymus-dependent form of B512 dextran requires the presence of Lyb-5+ lymphocytes.

Studies of the ontogeny of the immune response to B512 dextran (Dex) show that antibody responses equal to those of adult mice are not attained until 12 wk of age. We have examined the anti-Dex response after immunization with a thymus-dependent antigen isomaltohexaosyl-keyhole limpet hemocyanin (IM6-KLH) and have shown that the development of the cross-reacting anti-Dex response parallels the development of Lyb-5+ B cells. Adult levels of anti-Dex antibody after immunization with IM6-KLH are achieved in mice between 3 and 12 wk of age, a time when Lyb-5+ cells have reached adult levels. Neonatal mice, immunized at 1 d or 1 wk after birth, failed to produce a significant amount of anti-Dex antibodies, although they did produce IM6-specific antibodies after immunization with IM6-KLH. Data, which support the conclusion from these experiments that Lyb-5+ cells are required for an anti-polysaccharide response even when the immunizing antigen is thymus-dependent, include the failure of IM6-KLH to stimulate a normal anti-Dex response in mice with the xid defect and the direct demonstration in normal adult mice that elimination of Lyb-5+ cells from spleens of mice primed with IM6-KLH abolishes the ability of these cells to transfer an anti-Dex response. The data imply that the expressed B cell repertoire in adult animals is skewed such that the vast majority of B cells capable of responding to polysaccharide determinants are in the Lyb-5+ subset.

Animals↗
PubMed1982

The immune response to an isomaltohexosyl-protein conjugate, a thymus-dependent analogue of alpha(1 replaced by 6) dextran.

Two oligosaccharides derived from B512 dextran (Dex), isomaltohexaose (IM6), and isomaltotriose (IM3) have been coupled to keyhole limpet hemocyanin (KLH) and the conjugates studied as thymus-dependent (TD) immunogens analogous in their specificity to Dex. Both IM3-KLH and IM6-KLH stimulate an anti-Dex response in CBA mice. In C57BL mice, only IM6-KLH stimulated an anti-Dex response; IM3-KLH, although immunogenic, failed to elicit the production of anti-Dex antibodies. Similarly, CBA anti-Dex antibodies cross-reacted with both IM3 and IM6 coupled to bovine serum albumin (BSA), whereas C57BL anti-Dex antibodies cross-reacted with IM6-BSA and bound IM3-BSA only very poorly. This reciprocal lack of cross-reactivity between IM3 conjugates and Dex in C57BL mice was controlled by genes linked to the IgH locus, as shown in responses of allotype congenic CBA mice. This genetically regulated fine specificity pattern was overridden when IM6-KLH was used for immunization. C57BL antibodies that bound both Dex and IM3-BSA were produced in response to this antigen. Thus, isomaltohexosyl-protein conjugates provide Dex-like antigens that differ from Dex itself in terms of thymus dependency and the fine specificity of the precursors that are activated. They should provide important tools to study the activation requirements of antigen-specific B cells.

Animals↗
PubMed1981

A dynamic splint for use after total wrist arthroplasty.

Total wrist arthroplasty has been performed at the Mayo Clinic for the past 5 years. The procedure has necessitated the development of a dynamic wrist splint for post-operative care. This article provides a step-by-step outline for construction of this splint.

Arthritis, Rheumatoid↗
PubMed1978

o,p'-DDD (mitotane) therapy of adrenal cortical carcinoma: observations on drug dosage, toxicity, and steroid replacement.

Four patients with adrenal cortical carcinoma were treated with standard doses of o,p'-DDD. Plasma levels of o,p'-DDD and its metabolites o,p'-DDA and o,p'-DDE were measured. o,p'-DDD was measurable for up to 8 months after stopping therapy, and trace levels of metabolites were detectable at 18 months. Although 2 of 3 patients with measurable disease had objective tumor response and one patient achieved a complete response, severe drug toxicity occurred in all patients and signs of adrenal insufficiency occurred in three. Low dose therapy with o,p'-DDD is suggested, together with full gluco and mineralocorticoid replacement. Measurement of o,p'-DDD and its metabolites in plasma may prove clinically useful in developing effective but less toxic dosage schedules.

Adrenal Cortex Neoplasms↗
PubMed1977

Aryl and heterocyclic diazo compounds as potential environmental electrophiles.

4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.

Animals↗
PubMed1975

Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.

The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.

Age Factors↗
PubMed1975

Effect of deoxyuridine coadministration on toxicity and antitumor activity of fluorouracil and floxuridine.

The addition of deoxyuridine (UDR) to fluorouracil (FU) or floxuridine (5-fluoro-2' deoxyuridine) (FUDR) produced a substantial increase in their toxicity in BDF1 mice. Antitumor assays using sarcoma 180 tumor-bearing mice showed a concomitant increase in tumor growth inhibition for the nucleoside-drug combination over identical doses of the single drug. However, no significant increase in antitumor activity with the combination treatment was demonstrated when equitoxic doses were given. Additional support for the therapeutic equality of the single and combination drug regimens was the similarity of the therapeutic indexes for each treatment regimen involving either fluorouracil or floxuridine. The results suggested that any therapeutic benefit achieved with the combination therapy could be duplicated with either fluorouracil or floxuridine at a higher dose.

Animals↗
PubMed1975

The use of radioactive microspheres to compare the effects of hydralazine, guanethidine and SK & F 24260 on the redistribution of cardiac output in anaesthetized rabbits.

1 The use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure. 2 Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys. 3 SK&F 24260, (1,4 dihydro-2, 6-dimethyl-4(2-trifluoremethylpheny)-3,5,-pyridinedicarboxylic acid diethyl ester), had similar vasocilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation. 4 Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output.

Anesthesia↗