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Biomedical subjects

M J Mueller

Publications and source records attributed to M J Mueller.

At least 55 records · Page 3Linked to original sources
PubMed1996

Identifying patients with diabetes mellitus who are at risk for lower-extremity complications: use of Semmes-Weinstein monofilaments.

Research indicates that the SW monofilament is an inexpensive, reliable, valid, and easy-to-use clinical indicator for identifying patients who are at risk for developing foot ulcers and subsequent amputations. Those patients unable to sense the 5.07 SW monofilament on any part of their foot should be provided preventive care, including patient education and prescription of appropriate therapeutic footwear.

Diabetic Foot↗
PubMed1995

Leukotriene A4 hydrolase: mapping of a henicosapeptide involved in mechanism-based inactivation.

Leukotriene A4 (LTA4) hydrolase [7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9 ,11,14-tetraenoate hydrolase; EC 3.3.2.6] is a bifunctional zinc metalloenzyme which converts LTA4 into the chemotactic agent leukotriene B4 (LTB4). Suicide inactivation, a typical feature of LTA4 hydrolase/aminopeptidase, occurs via an irreversible, apparently mechanism-based, covalent binding of LTA4 to the protein in a 1:1 stoichiometry. Differential lysine-specific peptide mapping of unmodified and suicide-inactivated LTA4 hydrolase has been used to identify a henicosapeptide, encompassing the amino acid residues 365-385 of human LTA4 hydrolase, which is involved in the binding of LTA4, LTA4 methyl ester, and LTA4 ethyl ester to the native enzyme. A modified form of this peptide, generated by lysine-specific digestion of LTA4 hydrolase inactivated by LTA4 ethyl ester, could be isolated for complete Edman degradation. The sequence analysis revealed a gap at position 14, which shows that binding of the leukotriene epoxide had occurred via Tyr-378 in LTA4 hydrolase. Inactivation of the epoxide hydrolase and the aminopeptidase activity was accompanied by a proportionate modification of the peptide. Furthermore, both enzyme inactivation and peptide modification could be prevented by preincubation of LTA4 hydrolase with the competitive inhibitor bestatin, which demonstrates that the henicosapeptide contains functional elements of the active site(s). It may now be possible to clarify the molecular mechanisms underlying suicide inactivation and epoxide hydrolysis by site-directed mutagenesis combined with structural analysis of the lipid molecule, covalently bound to the peptide.

Amino Acid Sequence↗
PubMed1995

Evidence for a catalytic role of tyrosine 383 in the peptidase reaction of leukotriene A4 hydrolase.

Leukotriene A4 (LTA4) hydrolase is a bifunctional zinc metalloenzyme which catalyzes the final step in the biosynthesis of the proinflammatory leukotriene B4 and which also possesses a peptidase activity. From sequence comparisons with aminopeptidases, a tyrosine at position 383 in LTA4 hydrolase has been suggested as a possible catalytic amino acid. To explore the potential role of this amino acid in catalysis, we replaced the tyrosine residue with phenylalanine, histidine or glutamine residues by site-directed mutagenesis. The mutated cDNAs were expressed in Escherichia coli and the resulting recombinant proteins, named [Y383F]LTA4 hydrolase, [Y383H]LTA4 hydrolase and [Y383Q]LTA4 hydrolase, were purified to homogeneity to allow assays of both the epoxide hydrolase activity, i.e. the conversion of LTA4 into leukotriene B4, and the peptidase activity. None of the mutated proteins exhibited significant peptidase activities, all of them showing activities less than 0.3% that of the wild-type enzyme. The epoxide hydrolase activity was not affected to the same degree and corresponded to 11, 16 and 17% that of the unmutated enzyme for [Y383F]LTA4 hydrolase, [Y383H]LTA4 hydrolase and [Y383Q]LTA4 hydrolase, respectively. Kinetic analysis was performed with the mutant [Y383Q]LTA4 hydrolase, which revealed an approximately 10-fold increase in Km for leukotriene A4 compared to that for the unmutated enzyme. At high concentrations of substrate, the difference in enzyme velocity was only moderate, with Vmax values of 600 nmol.mg-1.min-1 and 1000 nmol.mg-1.min-1 for [Y383Q]LTA4 hydrolase and the wild-type enzyme, respectively. No such effect of substrate concentration could be observed on the peptidase activity. As a positive control, we exchanged a glycine residue in position 386 for an alanine residue, and the recombinant protein, [G386A]LTA4 hydrolase retained 19% and 77% of the peptidase and epoxide hydrolase activities, respectively. The results from this study are consistent with a role for Tyr383 in the peptidase reaction of LTA4 hydrolase, where it may act as a proton donor in a general base mechanism. However, our data do not allow a similar interpretation for the mechanism involved in the hydrolysis of LTA4 into LTB4.

Amino Acid Sequence↗
PubMed1995

The octadecanoic pathway: signal molecules for the regulation of secondary pathways.

Plant defense against microbial pathogens and herbivores relies heavily on the induction of defense proteins and low molecular weight antibiotics. The signals between perception of the aggression, gene activation, and the subsequent biosynthesis of secondary compounds are assumed to be pentacylic oxylipin derivatives. The rapid, but transient, synthesis of cis-jasmonic acid was demonstrated after insect attack on a food plant and by microbial elicitor addition to plant suspension cultures. This effect is highly specific and not caused by a number of environmental stresses such as light, heavy metals, or cold or heat shock. Elicitation of Eschscholtzia cell cultures also led to a rapid alkalinization of the growth medium prior to jasmonate formation. Inhibition of this alkalinization process by the protein kinase inhibitor staurosporine also inhibited jasmonate formation. The induction of specific enzymes in the benzo[c]phenanthridine alkaloid pathway leading to the antimicrobial sanguinarine was induced to a qualitatively and quantitatively similar extent by fungal elicitor, methyl jasmonate, and its linolenic acid-derived precursor 12-oxophytodienoic acid. It is herein proposed that a second oxylipid cascade may exist in plants starting from linoleic acid via 15,16-dihydro-12-oxophytodienoic acid to 9,10-dihydrojasmonate. Experiments with synthetic trihomojasmonate demonstrated that beta-oxidation is not a prerequisite for biological activity and that 12-oxophytodienoic acid and derivatives are most likely fully active as signal transducers. Octadecanoic acid-derived compounds are essential elements in modulating the synthesis of antibiotic compounds and are thus integral to plant defense.

Animals↗
PubMed1995

Chemical modification of leukotriene A4 hydrolase. Indications for essential tyrosyl and arginyl residues at the active site.

We have employed chemical modification to identify amino acids essential for the catalytic activities of the bifunctional zinc metalloenzyme leukotriene A4 hydrolase (EC 3.3.2.6). The epoxide hydrolase and the peptidase activity were both rapidly inactivated by N-acetylimidazole and tetranitromethane. Furthermore, treatment with 2,3-butanedione and phenylglyoxal also resulted in loss of both activities. Leukotriene A4 hydrolase could be protected from inactivation by these tyrosyl and arginyl reagents by the competitive inhibitors bestatin and captopril, respectively. Two tyrosyl and three arginyl residues were found by differential labeling techniques to be protected by the inhibitors, which thus suggested that these amino acids are located close to or at the active center of the enzyme. Limited modification by thiol reagents and particularly methyl methanethiosulfonate led to a > 10-fold increase in the peptidase activity and a decreased epoxide hydrolase activity, whereas prolonged treatment inhibited both activities. Kinetic analysis of modified enzyme, using the substrate alanine p-nitroanilide, revealed that the stimulatory effect on the peptidase activity was due to increased enzyme displayed a reduced apparent affinity constant for chloride ions, which strongly stimulate the peptidase activity. Neither activation nor inactivation by methyl methanethiosulfonate was influenced by the presence of competitive inhibitors, which suggested that this compound did not react with amino acids at the active center but rather with residues of importance for the overall enzyme conformation.

Arginine↗
PubMed1995

Incidence of skin breakdown and higher amputation after transmetatarsal amputation: implications for rehabilitation.

The purpose of this study of patients with transmetatarsal amputation (TMA) is to describe multiple patient characteristics, including the incidence of subsequent skin breakdown and higher amputation, that may influence rehabilitation treatment and outcomes. Data were gathered on all patients having a TMA at this facility between April 1989 and September 1993. One hundred twenty TMAs were performed on 107 patients with a mean age of 62.4 +/- 13.8 years. There were 55 men and 52 women. Thirteen patients (12%) had a bilateral TMA. Twenty-nine patients (27%) developed skin breakdown. Of these, 48% occurred within the first 3 months after surgery. Thirty patients (28%) required a higher amputation. Of these, 60% occurred in the first month after TMA. In addition, this group of patients had a high incidence of diabetes mellitus (77%), hypertension (54%), electrocardiogram (EKG) abnormalities (60%), congestive heart failure (22%), and prior ipsilateral vascular surgery (51%). These results indicate that patients with TMA often present with a complicated medical condition and that they are at high risk of skin breakdown or higher amputation, especially in the first 3 months after surgery. The investigators conclude that patients with TMA may benefit from a rehabilitation program emphasizing protection of the residuum during their return to functional activities. Additional research is needed to determine optimal acute and long-term rehabilitation of patients with TMA.

Amputation, Surgical↗
PubMed1995

Relationship of plantar-flexor peak torque and dorsiflexion range of motion to kinetic variables during walking.

BACKGROUND AND PURPOSE: Limited ankle plantar-flexor moments and power during walking have been documented in several patient populations and are believed to contribute to gait deviations. The primary purpose of this study was to determine the relationship of plantar-flexor peak torque (PFPT) and dorsiflexion range of motion (ROM) to peak ankle moments and power during walking in a group of subjects without diabetes mellitus (DM) and in a group of subjects with DM and associated peripheral neuropathies. SUBJECTS: Nineteen subjects, 9 with DM and associated peripheral neuropathies (mean age = 58 years, SD = 14, range = 35-75 years) and 10 without DM (mean age = 57 years, SD = 11, range = 37-68 years), were evaluated. METHODS: The following data were collected on all subjects: PFPT, dorsiflexion ROM, and ankle moments and power during walking (using a two-dimensional link-segment model). Hierarchical multiple regression was used for data analysis. RESULTS: Plantar-flexor peak torque made substantial contributions to the ankle moment (40%) and ankle plantar-flexor power (53%) during walking. There also was a high correlation between PFPT and dorsiflexion ROM (r = .78) and between dorsiflexion ROM and ankle power (r = .72). CONCLUSION AND DISCUSSION: Plantar-flexor peak torque and dorsiflexion ROM are interrelated and appear to be important factors that contribute to ankle plantar-flexor moments and power during walking. This finding suggests that increasing PFPT and dorsiflexion ROM may help decrease gait deviations such as decreased step length and walking speed. When increasing PFPT is not possible, the natural occurrence of limited dorsiflexion ROM may help to maximize ankle moments during walking. Further research is needed to test whether these proposed treatment strategies can have a clinically useful effect. [Mueller MJ, Minor SD, Schaaf JA, et al. Relationship of plantar-flexor peak torque and dorsiflexion range of motion to kinetic variables during walking.

Adult↗
PubMed1995

Use of an in-shoe pressure measurement system in the management of patients with neuropathic ulcers or metatarsalgia.

Many injuries to the foot appear to be caused by repeated, excessive plantar pressures. In-shoe pressure systems are capable of measuring pressures at the interface between the shoe or orthotic and the plantar foot during a given functional activity. The purpose of this article is to describe the use of an in-shoe pressure system as a tool to aid physical therapists in the management of patients with foot problems as a result of excessive plantar pressures. Case histories are provided that describe the application of an in-shoe pressure device in the management of one patient with a neuropathic ulcer and one patient with metatarsalgia. A discussion of the primary clinical and equipment considerations of using this type of device is included.

Aged↗
PubMed1994

Quantification of jasmonic acid by capillary gas chromatography-negative chemical ionization-mass spectrometry.

Jasmonic acid can be assayed by the highly sensitive and reproducible gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) technique. We describe an optimized sample preparation method for routine analysis of jasmonic acids which allows the analysis of more than 10 samples/day. The basis of the method resides in a one-step extraction and phase partition, selective adsorption/elution of acids with an aminopropyl column, conversion of acids to pentafluorobenzyl esters, final purification using a silica column, and GC-NICI-MS. Extracted standard curves were linear over an assay range of 1 to 1000 ng; correlation coefficients were typically greater than 0.9999. The limit of detection was 500 fg (2.4 fmol) jasmonic acid/injection at a signal to noise ratio of 10:1. Furthermore, the method was modified for steric analysis of jasmonic acid stereoisomers at the nanogram level. (3R,7S)-(+)-7-Iso-jasmonic acid was found to be biosynthesized from plant tissue cell cultures upon elicitation. This stereoisomer epimerizes rapidly under alkaline and acidic conditions and in the presence of albumin. Epimerization rate constants were determined at different pH values.

Cells, Cultured↗
PubMed1994

Hip and ankle walking strategies: effect on peak plantar pressures and implications for neuropathic ulceration.

Treatment of neuropathic plantar ulcers often is directed at reducing excessive, repeated peak plantar pressures (PPP). The purposes of this study were to determine whether instructing a subject to walk using a hip strategy would reduce forefoot PPP and change the kinematics of walking during a single session of testing. Thirteen subjects, 7 with peripheral neuropathy and a history of a recent plantar ulcer, and 6 controls participated. PPPs were measured with an in-shoe pressure monitoring system. Kinematics were measured with a computer-assisted motion analysis system. After data were collected as subjects walked using their normal walking pattern, subjects were instructed to walk using the hip strategy by decreasing their push-off, pulling their leg forward from their hips, decreasing step length, and maintaining their normal walking velocity. Compared with using the normal (ankle) strategy, using the hip strategy showed a significant 27% decrease in forefoot PPP and a 24% increase in heel PPP. Kinematic changes were decreased plantar flexion angular velocity, hip extension range-of motion (ROM), and step length, increased dorsiflexion ROM, and hip flexion ROM, but no change in walking velocity. These findings indicate that a change in walking pattern can result in lower forefoot PPP during a single session. Assuming patients can maintain the alterations in their walking pattern, these adaptations may help to heal plantar ulcers in some patients with peripheral neuropathy.

Adult↗
PubMed1994

Rehabilitation factors following transmetatarsal amputation.

Despite the occurrence of approximately 10,000 transmetatarsal amputations (TMAs) a year in the United States, there are few reports describing rehabilitation for this patient group. The purposes of this clinical perspective are (1) to identify common problems encountered during rehabilitation of patients with TMA, (2) to identify factors that may contribute to these problems, and (3) to propose methods to manage these problems. A review of the literature and biomechanical models of the residuum, footwear, and orthotic devices are provided to help accomplish these purposes. Common problems encountered during rehabilitation of patients with TMA are skin breakdown and instability during functional activities. Decreased foot length and peripheral neuropathies appear to contribute to these problems. Solutions focus on attempting to provide a substitute for the plantar-flexor lever arm and protection of the insensitive residual foot. Suggestions for additional research are presented.

Accidental Falls↗
PubMed1994

Differences in the gait characteristics of patients with diabetes and peripheral neuropathy compared with age-matched controls.

BACKGROUND AND PURPOSE: Patients with diabetes and peripheral neuropathy have a high incidence of injuries while walking. Biomechanical analysis of their walking may lead to treatments to reduce these injuries. The purpose of this study was to compare (1) the gait characteristics, (2) the plantar-flexor peak torques, and (3) the ankle range of motion of subjects with diabetes mellitus (DM) and peripheral neuropathy with those of age-matched controls. SUBJECTS: Twenty subjects, 10 with DM and a history of peripheral neuropathy (DM group) (mean age = 58 years, SD = 15, range = 35-75) and 10 subjects without diabetes (NODM group) (mean age = 57 years, SD = 11, range = 37-68), were evaluated. METHODS: The following data were collected on all subjects: ankle joint mobility, plantar-flexor peak torque (ankle strength), kinematics of the trunk and lower extremity during normal walking, and ground reaction forces. Moments and power at the ankle, knee, and hip during walking were calculated using a two-dimensional link-segment model. RESULTS: The DM group subjects showed less ankle mobility, ankle moment, ankle power, velocity, and stride length during walking than the NODM group subjects. A significant decrease in ankle strength and mobility appeared to be the primary factor contributing to the altered walking patterns of the DM group. CONCLUSION AND DISCUSSION: The DM group subjects appeared to pull their legs forward using hip flexor muscles (hip strategy) rather than pushing the legs forward using plantar-flexor muscles (ankle strategy), as seen in the NODM group subjects. Implications for treatment are presented to attempt to reduce the number of injuries during walking in patients with DM and peripheral neuropathy.

Adult↗
PubMed1994

Shin splints and forefoot contact running: a case report.

Many athletes develop shin splints after athletic activity. The purpose of this case report is to describe the treatment of a patient with posteromedial tibial pain (shin splints) who habitually ran with a forefoot contact running style. The 20-year-old male patient, who played volleyball and basketball about 7 hours a week, complained of pain in the middle one-third of the posteromedial tibia after an acute but prolonged episode of running. Routine observational analysis and in-shoe pressure analysis of the patient's running style showed that he habitually ran on his toes with an absence of heelstrike (forefoot contact running). After instructing the patient on heel-toe running, he no longer complained of posteromedial tibial bone pain. Several possible reasons are proposed for the reduction of leg pain following cessation of forefoot contact running. This case report proposes forefoot contact running as a possible contributor to posteromedial shin splints and that a change in running style may be the optimal treatment for some patients.

Adult↗
PubMed1993

Signaling in the elicitation process is mediated through the octadecanoid pathway leading to jasmonic acid.

Fungal cell walls and fragments thereof (elicitors) induce the formation of low and high molecular weight defense compounds in plant cell suspension cultures. This induced synthesis requires a signal molecule transmitting the message between the elicitor plant cell wall receptor and gene activation. We demonstrate in this study that cis-jasmonic acid is rapidly synthesized in plant cell cultures of diverse taxonomic origin (gymnosperms and mono- and dicotyledonous plants) after challenge with a fungal elicitor preparation. The rapid decline of cis-jasmonic acid in some of these tissues is attributed to rapid metabolism of this pentacyclic acid. The induction of alkaloids by several different molecules provoking the elicitation process is strictly correlated with the synthesis of jasmonates. Elicitation leads to a rapid release of alpha-linolenic acid from the lipid pool of the plant cell. alpha-Linolenic acid and 12-oxophytodienoic acid, the formation of which is also induced, are known to be distant precursors of jasmonic acid. We assume cis-jasmonic acid and its precursors to be the signaling molecules in the elicitation process.

Journal Article↗
PubMed1993

Effect of total contact cast immobilization on subtalar and talocrural joint motion in patients with diabetes mellitus.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of total contact casting (TCC) on dorsiflexion at the talocrural joint (TCJ) and motion (inversion/eversion) at the subtalar joint (STJ). SUBJECTS: Thirty-seven patients (29 men, 8 women), ranging in age from 32 to 79 years (mean = 54, SD = 11), with diabetes mellitus and a unilateral plantar ulceration participated in the study. METHODS: The subjects were measured with a goniometer for dorsiflexion and STJ range of motion (ROM). The ROMs for each subject's casted and noncasted legs were compared before and after treatment with TCC for neuropathic plantar ulcers by use of a 2 x 2 repeated-measures analysis of variance design. RESULTS: Mean time of immobilization in TCC (healing time) was 42 days (SD = 43, range = 8-119). The results indicated (1) ROM was unchanged at the STJ, but dorsiflexion decreased slightly (1 degree) on both the casted and noncasted sides following the last cast removal, and (2) ROM was less on the ulcerated side prior to casting compared with the nonulcerated side. CONCLUSION AND DISCUSSION: We believe the beneficial effects (healing of wounds) outweigh the minimal detrimental effects (decreased dorsiflexion) of treatment with TCC.

Adult↗
PubMed1993

Navicular drop as a composite measure of excessive pronation.

The measure of navicular drop has been used as an indicator of pronation at the foot. It is defined as the distance the navicular tuberosity moves in standing, as the subtalar joint is allowed to move from its neutral position to a relaxed position. The purposes of this study were to test the reliability of a method to measure navicular drop and to assess the relationships among measures of forefoot to rearfoot position, subtalar joint neutral position, and navicular drop. The results support traditional biomechanical theory but indicate that other factors contribute significantly to navicular drop.

Adult↗
PubMed1992

Reliability of kinematic measurements of rear-foot motion.

The purpose of this study was to examine the ability of a video-based, computer-interfaced motion analysis system to provide reliable data. Ten subjects with no significant orthopedic or neurological dysfunction and ranging in age from 22 to 45 years (mean = 29.6, SD = 7.8) were tested. Retroreflective markers were placed on the posterior shank and foot of each subject. Footswitches were attached to the plantar forefoot and rear foot. A video camera was placed behind the subject, and video data were collected while the subject walked on a treadmill. One representative gait cycle for each subject was selected and processed 10 times with a video processor and analysis software. Three intraclass correlation coefficients (ICCs) were calculated for variables generated by the analysis software, one for two individual measures and one each for the mean of three and five repeated measures. Except for temporal variables, processing data introduced additional variability into the measurement process, particularly for angular velocity data. Measurement of all variables was highly reliable (ICC values greater than or equal to .95) when based on the mean of at least three repeated measures. Although a single measure of temporal and angular position variables may be considered reliable, we recommend using a mean of three trials for angular velocity variables. Additional research is needed to determine tester and subject variability and validity of the measures.

Adult↗