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Biomedical subjects

M Petersen

Publications and source records attributed to M Petersen.

At least 55 records · Page 3Linked to original sources
PubMed1998

The proportion of isolated rat dorsal root ganglion neurones responding to bradykinin increases with time in culture.

The proportion of isolated rodent dorsal root ganglion neurones expressing bradykinin receptors increases transiently with time in culture. However, it has not yet been investigated whether these receptors are functioning. Therefore the responses of these neurones to bradykinin (1 microM) were investigated in patch-clamp experiments in the current clamp mode after 0.8 and 1.8 days under culture conditions. The proportion of neurones responding to bradykinin was 26% (5/19) at day 0.8 and increased to 73% (16/22) at day 1.8. The intensity of the response was assessed by counting the number of action potentials evoked by bradykinin within four fixed intervals of 500 ms duration during each experiment. It increased with time in culture from an average of 8 +/- 2 (SD) at day 0.8 to 16 +/- 6 at day 1.8, respectively. These results provide evidence for the induction of functioning bradykinin receptors in cultured dorsal root ganglion neurones with time in culture.

Action Potentials↗
PubMed1998

Two sequence-ready contigs spanning the two copies of a 200-kb duplication on human 21q: partial sequence and polymorphisms.

Physical mapping across a duplication can be a tour de force if the region is larger than the size of a bacterial clone. This was the case of the 170- to 275-kb duplication present on the long arm of chromosome 21 in normal human at 21q11.1 (proximal region) and at 21q22.1 (distal region), which we described previously. We have constructed sequence-ready contigs of the two copies of the duplication of which all the clones are genuine representatives of one copy or the other. This required the identification of four duplicon polymorphisms that are copy-specific and nonallelic variations in the sequence of the STSs. Thirteen STSs were mapped inside the duplicated region and 5 outside but close to the boundaries. Among these STSs 10 were end clones from YACs, PACs, or cosmids, and the average interval between two markers in the duplicated region was 16 kb. Eight PACs and cosmids showing minimal overlaps were selected in both copies of the duplication. Comparative sequence analysis along the duplication showed three single-basepair changes between the two copies over 659 bp sequenced (4 STSs), suggesting that the duplication is recent (less than 4 mya). Two CpG islands were located in the duplication, but no genes were identified after a 36-kb cosmid from the proximal copy of the duplication was sequenced. The homology of this chromosome 21 duplicated region with the pericentromeric regions of chromosomes 13, 2, and 18 suggests that the mechanism involved is probably similar to pericentromeric-directed mechanisms described in interchromosomal duplications.

Cell Line↗
PubMed1998

Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.

Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.

ADAM Proteins↗
PubMed1998

Nerve growth factor regulates the expression of bradykinin binding sites on adult sensory neurons via the neurotrophin receptor p75.

Neurotrophins mediate specific effects on sensory neurons through tyrosine kinase receptors. Most of these neurons also co-express the neurotrophin receptor p75 (p75NTR), but its function has remained obscure. We now show that nerve growth factor but not brain-derived neurotrophic factor or neurotrophin-3 selectively increases the expression of bradykinin binding sites on cultured dorsal root ganglion neurons from adult mouse via p75NTR. This up-regulation of bradykinin binding sites did not occur in neurons from mice lacking p75NTR or in neurons from wild-type mice treated with p75NTR-blocking antibody, indicating that tyrosine kinase receptors alone are not sufficient to trigger this physiological neuronal response. Thus, the interaction of nerve growth factor with p75NTR is an important factor contributing to chronic pain conditions.

Animals↗
PubMed1998

Plasticity in the expression of bradykinin binding sites in sensory neurons after mechanical nerve injury.

The pro-inflammatory mediator bradykinin plays an important role in hyperalgesia during inflammatory conditions. Here, we used unilateral ligation of the sciatic nerve to investigate whether the expression of bradykinin binding sites in isolated rat dorsal root ganglion neurons is changed following nerve injury. Under control conditions, the percentage of neurons expressing bradykinin binding sites increased from 52% at day 0.8 in culture to 93% at day 1.8 and decreased to 67% at day 3.8. Following nerve ligation either two or 10 days prior to the isolation of the somata, the percentage of neurons from ipsilateral ganglia that expressed bradykinin binding sites was already 87% and 86%, respectively, at day 0.8 in culture; this level was maintained at day 1.8 and decreased slightly at day 3.8. In control neurons, high densities of bradykinin binding sites on individual neurons were observed no sooner than at day 1.8, but already at day 0.8 following nerve ligation, due to a "de novo" expression of B1 receptors and augmentation of B2 receptors. Neurons from the contralateral side responded similarly to ipsilateral neurons after a two day nerve ligation, however, after either a 10 day ligation or a sham operation neurons responded similarly to control neurons. These data are the first evidence that expression of B1 receptors is induced and expression of B2 receptors is enhanced in sensory neurons following nerve ligation. Under pathophysiological conditions, increased expression of subtypes of bradykinin receptors in sensory neurons could contribute to chronic pain conditions.

Animals↗
PubMed1998

A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR.

The vaccinia virus A39R protein is a member of the semaphorin family. A39R.Fc protein was used to affinity purify an A39R receptor from a human B cell line. Tandem mass spectrometry of receptor peptides yielded partial amino acid sequences that allowed the identification of corresponding cDNA clones. Sequence analysis of this receptor indicated that it is a novel member of the plexin family and identified a semaphorin-like domain within this family, thus suggesting an evolutionary relationship between receptor and ligand. A39R up-regulated ICAM-1 on, and induced cytokine production from, human monocytes. These data, then, describe a receptor for an immunologically active semaphorin and suggest that it may serve as a prototype for other plexin-semaphorin binding pairs.

Amino Acid Sequence↗
PubMed1998

Sit-to-stand manoeuvre in hemiparetic patients before and after a 4-week rehabilitation programme.

The objective of the study was to document the sit-to-stand of 35 moderately affected hemiparetic patients before and after a 4-week inpatient rehabilitation programme and to investigate the influence of the side of hemiparesis and impaired proprioception on its outcome. The therapists trained the patients to distribute equal weight on both legs and to avoid lateral compensatory tilt of the trunk. The body weight distribution and the displacement of the centre of mass in the frontal plane were studied by assessment of triaxial ground reaction forces. Symmetrical weight acceptance and minimal lateral sway were not reached during the 4-week rehabilitation, with the exception of the patients with a left hemiparesis (n = 19) and no proprioceptive deficit (n = 18).

Aged↗
PubMed1998

Immunological markers among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

OBJECTIVES: To examine the association of immune cell number and function with occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). METHODS: A cross sectional medical survey. The exposed participants were employed at two chemical plants between 1951 and 1972 in the manufacture of 2,4,5-trichlorophenate and its derivatives. The reference group consisted of people with no occupational exposure to phenoxy herbicides who lived within the communities of the workers. Data from a total of 259 workers and 243 unexposed referents were included in the analysis of immune function. Laboratory tests for immune status included enumeration of circulating leukocyte and lymphocyte populations, proliferative responses of circulating lymphocytes to mitogens and antigens, and serum concentrations of the major immunoglobulins and complement factor C3. RESULTS: The workers had substantial exposure to substances contaminated with TCDD, as indicated by a lipid adjusted mean serum TCDD concentration of 229 ppt compared with a mean of 6 ppt in the unexposed referents. Workers were divided into categories based on their serum TCDD concentration. For all categories except the lowest, with values of serum TCDD comparable with the unexposed referents, there were increased odds of having lower counts of CD26 cells (activated T cells) (odds ratio (OR) 1.0, 95% confidence interval (95% CI) 0.5 to 1.8 for TCDD < 20 ppt; OR 1.6, 95% CI 0.8 to 3.2 for TCDD 20-51 ppt; OR 2.7, 95% CI 1.4 to 5.1 for TCDD 52-125 ppt; OR 2.6, 95% CI 1.4 to 4.9 for TCDD 125-297 ppt; OR 2.4, 95% CI 1.3 to 4.6 for TCDD 298-3389 ppt). A less consistent finding was decreased spontaneous proliferation of cultured lymphocytes. However, increases were found in proliferation of lymphocytes in response to concanavalin and pokeweed in workers in the high TCDD category. Age, cigarette smoking, and alcohol were significant predictors of several immunological outcomes. CONCLUSIONS: Associations between serum TCDD concentration and both a decrease in circulating CD26 cells and decreased spontaneous background proliferation were the major findings of this study. These results are unlikely to be of clinical importance but may reflect limited evidence for an association between immunological changes in workers and high serum concentrations of TCDD, or chance findings resulting from the evaluation of multiple immunological variables.

Adult↗
PubMed1997

Projections from the renal nerve to the cat's lateral somatosensory thalamus.

The representation of the kidney in the lateral somatosensory thalamus was mapped using electrical stimulation of the renal nerve in pentobarbitone-anesthetized cats. Ninety-five of 197 thalamic neurons studied responded to renal nerve stimulation. The responsive neurons were located in the periphery of the ventral posterolateral nucleus (42%; VPLp) and the neighboring dorsal and lateral aspects of the posterior complex (58%; POd and POl). No visceroceptive neurons were found within VPL proper. The mean response latency of the thalamic neurons to electrical nerve stimulation was 9.5 +/- 2.6 ms (mean +/- S.D.), suggesting an involvement of A delta, and possibly A beta fibers in the primary afferent pathway. The visceroceptive neurons were further characterized with innocuous mechanical stimulation of the body surface, and for 94 of the 95 neurons a somatic receptive field could be determined. Of these, 35% were located on the lower back and belly, i.e., the dermatomes of the lower thoracic and upper lumbar spinal projection areas of the renal nerve. 52% of the somatic receptive fields were located on the contralateral foot, thigh, tail, or hind leg (lower lumbar, sacral and coccygeal dermatomes) and 13% covered the arm and upper body (upper thoracic and lower cervical dermatomes). Comparison between the thalamic representations of the renal and pelvic nerves showed that both covered comparable areas adjacent and around, but not within VPL proper. It is concluded that VPLp, POd and POl play a role in processing visceral, possibly including nociceptive, information from the kidney of the cat.

Animals↗
PubMed1997

Methylene blue induces ongoing activity in rat cutaneous primary afferents and depolarization of DRG neurons via a photosensitive mechanism.

The dye methylene blue is known as a blocker of guanylyl cyclase and it has been widely used to deplete cells of internal cyclic GMP. The data presented demonstrate an activation of adult rat sensory neurons by methylene blue via a photosensitive mechanism. In single fiber recordings from primary afferents of the rat skin in vitro, methylene blue, applied to the receptive field, induced discharge activity: 2/2 A beta-, 2/4 A delta- and 5/7 C-fibers showed significantly enhanced firing upon 10 microM methylene blue in the presence of light, whereas the dye was ineffective when illumination was prevented. In whole cell current clamp experiments with dissociated dorsal root ganglion neurons, 100 microM methylene blue was ineffective in the dark but evoked a membrane depolarization of 15.3 +/- 3.5 mV (n = 5) accompanied by discharge activity upon illumination. In whole cell voltage clamp experiments, methylene blue (100 microM) caused a significant slowing of the inactivation of voltage-dependent sodium currents. In addition, an inhibition of fast and slow outward currents was observed with prolonged exposure. The impeded sodium inactivation together with the blockade of potassium currents may contribute to the depolarization and discharge activity observed in primary afferents in vitro as well as in dissociated sensory neurons in culture. We therefore suggest that methylene blue studies with excitable cells or tissues need to be interpreted with caution.

Action Potentials↗
PubMed1997

[Endogenous Aspergillus endophthalmitis in AIDS].

BACKGROUND: We present the course of an endogenous Aspergillus endophthalmitis in a 38-year-old HIV-positive man. HISTORY AND CLINICAL SIGNS: The first examination because of a sudden visual loss in the right eye showed a central subretinal infiltration, peripheral vascular sheeting and retinal hemorrhages. THERAPY AND OUTCOME: In spite of high-dose systemic antifungal therapy we could not prevent the penetration of the posterior wall of the eye and infiltration of adjacent orbital structures. Enucleation had to be performed. CONCLUSIONS: In case of scleral involvement in Aspergillus endophthalmitis the necessity of enucleation has to be considered.

AIDS-Related Opportunistic Infections↗
PubMed1997

C5b-7 and C5b-8 precursors of the membrane attack complex (C5b-9) are effective killers of E. coli J5 during serum incubation.

The finding that C9-deficient sera (C9D) can kill serum sensitive strains of Gram-negative bacteria by us and other investigators, questions the role of C9 in the membrane attack complex as necessary for cell death. In these studies we have demonstrated that C5b-8 complexes generated on E. coli J5 during incubation in C9-depleted and C9-neutralized sera are effective in killing Gram-negative bacteria. In the same study, we extended our investigations to show that the deposition of C5b-7 complexes (from C8-deficient [C8D], C8 depleted and C8-neutralized sera) is also effective in killing Gram-negative bacteria. In all cases, these studies demonstrated that when E. coli J5 was incubated with C8D, C9D and pooled normal human serum [PNHS], deposited C5b-9 complexes from PNHS produced more killing than C5b-7 or C5b-8 complexes alone. These experiments clearly demonstrated that C5b-7 and C5b-8 complexes are bactericidal and that multimeric C9 within C5b-9 is not an absolute requirement for inner membrane damage and cell death of Gram-negative bacteria.

Blood Bactericidal Activity↗
PubMed1996

Mortality of Carpenters' Union members employed in the U.S. construction or wood products industries, 1987-1990.

This study evaluated the mortality of 27,362 members of the U.S. Carpenters' Union who died in 1987-1990. Age-adjusted proportionate mortality ratios (PMRs) and proportionate cancer mortality ratios (PCMRs) were computed using the U.S. age-, gender-, and race-specific proportional mortality for the years of the study. For white male carpenters who were last employed while in construction industry locals, raised mortality was observed for lung cancer (PCMR = 107, CI = 103, 111), bone cancer (PMR = 181, CI = 107, 286), asbestosis (PMR = 283, CI = 158, 457), emphysema (PMR = 115, CI = 102, 130), transportation injuries (PMR = 121, CI = 109, 135), and falls (PMR = 122, CI = 104, 142). For white male carpenters who were last employed while in industrial wood products locals, significantly raised mortality occurred for stomach cancer (PMR = 187, CI = 136, 250), male breast cancer (PCMR = 469, CI = 128, 720), and transportation injuries (PMR = 136, CI = 110, 173). Excess breast cancer was associated with last employment inn wood machining trades. Nasal cancer mortality was not elevated. A total of 121 mesotheliomas were observed. Contributing cause of death analyses revealed raised mortality for these and additional causes; 4,594 (18%) death certificates mentioned occupational and other lung disease as a contributing factor, resulting in significantly elevated mortality. These data show that construction carpenters have moderately elevated mortality for the diseases caused by asbestos (lung cancer and malignant mesothelioma) and from traumatic injuries. The finding of elevated mortality for stomach, bone, and breast cancer was unexpected and requires further evaluation of possible occupational factors. This study confirms that construction carpentry is an extremely hazardous trade. The data suggest that additional preventive action guarding against asbestos exposure and occupational injury is urgently needed in this occupation.

Accidental Falls↗
PubMed1996

Isolation and characterisation of a pod dehiscence zone-specific polygalacturonase from Brassica napus.

Seven distinct partial cDNAs, similar in sequence to previously described polygalacturonases (PGs), were amplified from cDNA derived from rape pod wall, dehiscence zone and leaves by the polymerase chain reaction. Northern analysis showed that one clone, PG35-8, was expressed at low levels in the dehiscence zone during the first five weeks after anthesis but was very abundantly expressed at week 6. In contrast, no PG35-8-related RNA was detected in the pod wall. Our data suggest that there are temporal and spatial correlations between the breakdown of the middle lamella, of the dehiscence zone cells and the pattern of synthesis of PG35-8 transcripts which may indicate a role for this particular PG in rape pod dehiscence. PG35-8 was used to isolate five cDNA clones from a rape dehiscence zone cDNA library. Restriction enzyme analysis and partial sequencing revealed that they were derived from four highly homologous transcripts which are probably allelic forms of a single gene. One full-length clone, RDPG1, was completely sequenced. The predicted protein of RDPG1 showed its highest identity with PG from apple fruit with an identity of 52%.

Amino Acid Sequence↗
PubMed1996

Abnormal spontaneous activity and responses to norepinephrine in dissociated dorsal root ganglion cells after chronic nerve constriction.

As a part of ongoing studies of the cellular mechanisms of sympathetically maintained pain, we investigated the effects of a peripheral nerve injury on the responses of dissociated dorsal root ganglion (DRG) cells to norepinephrine (NE). Whole-cell patch-clamp recordings under current clamp were obtained from L4 and L5 DRG cells from adult rats in acute culture 11-25 days after a loose or tight ligation of the sciatic nerve. Only small to medium-sized cells from normal (uninjured) nerves and from loosely ligated nerves were tested with NE. One of 15 cells obtained-from uninjured nerves responded to NE (500 microM, the highest dose, elicited a small depolarization without action potentials). In contrast, many cells from injured nerves responded to NE with a membrane depolarization, accompanied in some cases by the generation of action potentials. Fifty-two percent responded to 500 microM, while a significantly lower percentage responded to the lower doses of 100 microM (26%) and 10 microM (14%). Cells responsive to NE also responded to capsaicin. Spontaneous activity was observed in 14% and 21% of cells from loosely and tightly ligated nerves, respectively, but none of the cells from uninjured nerves. We conclude that the abnormal electrogenesis and responsiveness to NE in certain nerve-injured primary sensory neurons are due at least in part to changes in the membrane properties of the soma.

Adrenergic alpha-Agonists↗
PubMed1996

Multiple capsaicin-evoked currents in isolated rat sensory neurons.

The response to capsaicin in functional assays suggests multiple sites of capsaicin action. This hypothesis is supported by the results of the present patch-clamp study of isolated dorsal root ganglion cells of the rat. The response to a prolonged application of capsaicin of different concentrations in an external solution with different ion compositions was investigated. Capsaicin evoked up to three distinct current components. The first and second current components could be activated independently. The third component occurred only in the presence of sodium and only in cells in which the second component was also elicited. In an extracellular solution with a physiological composition of ions and 300 nM capsaicin, the peaks of the three components, when evoked, occurred at 10.1 +/- 1.35 s (mean +/- S.E.M., n = 9), 44.0 +/- 2.64 s (n = 16) and 79.0 +/- 8.10 s (n = 5). The activation of the first and/or second current component depended on the concentration of capsaicin. A low concentration predominantly elicited the second component, while a high concentration activated the first and suppressed the second one. The third component seems to be a secondary response of the cell and was not investigated in detail. The activation and decay phases of the first two current components could be fitted by single exponential functions, whereas those of the third component could not. The first and second current components were carried by sodium and calcium. After tachyphylaxis, if the extracellular medium was then acidified to a pH of 6.3, the second component alone could then be elicited by capsaicin. The results demonstrate that capsaicin can elicit different current components that are distinguishable by their time-course, by the effects of acidification of the extracellular solution and by the concentration of capsaicin required to activate these currents. We postulate two distinct binding sites of capsaicin causing two distinct current components. This may account for the variety of physiological responses evoked by capsaicin and the variations in these responses between species.

Animals↗
PubMed1996

Bradykinin receptors in cultured rat dorsal root ganglion cells: influence of length of time in culture.

The endogenous nonapeptide bradykinin is a powerful substance which activates nociceptors, resulting in the sensation of pain in man. We used a newly developed non-radioactive method to detect bradykinin binding sites in isolated dorsal root ganglion cells with gold-labelled bradykinin. In a subpopulation of cells, gold-labelled bradykinin was bound in different quantities. The proportion of somata with bradykinin binding markedly depended on the length of time in culture. After 0.75 days, bradykinin was bound to 43% of somata. This proportion increased to 85% after 1.75 days and then decreased to 27% after 5.75 days. Bradykinin was bound to cells of all sizes, ranging from 40 to 2000 microns2 with a maximum of 200-300 microns2. In some cells, binding was also seen along the processes. No correlation was found between the soma size and the density of bradykinin binding. Blocking the bradykinin binding at the B1 receptor with (Des-Arg10)-Lys-bradykinin and at the B2 receptor with D-Arg(Hyp3-Thi5.8-D-Phe7)-bradykinin, respectively, revealed that in 0.75-day-old cultures no or only a very small amount of B1 receptors are present. In 1.75-day-old cultures, the marked increase in the proportion of cells with positive bradykinin binding is due to a de novo expression of the B1 receptor subtype and an up-regulation of the B2 receptor subtype. The selective or combined addition of specific B1 and B2 receptor ligands revealed that both receptor subtypes are co-localized. These data show that cultured sensory neurons express not only B2, but during a short period of time in culture also B1 receptors. The data allow us to hypothesize that a transient increase in bradykinin receptor expression might be caused by cell injury due to disruption of the axon. The injury-induced up-regulation of the receptor in vivo could cause physiological reactions.

Animals↗