Irx1 and Irx2 expression in early lung development.

We describe a comparative lung expression analysis of the murine Irx1 and Irx2 genes. At embryonic day 8.5 (E8.5), the Irx1 and Irx2 expression starts in the foregut region, where the laryngo-tracheal groove will form. The expression is prominent in the lung epithelium during glandular development. It declines at the end of the canalicular phase. We further compare the Irx1 and Irx2 expression domains to Gli1, 2, 3 and Mash1. Their homologues in Drosophila melanogaster are known as regulative partners of the iroquois complex. The Irx and Gli genes are coexpressed in the developing lungs at the same time. Their transcripts are not localised in the same cells but adjacent to each other in either mesenchymal or epithelial structures. It is thought that the lung development is regulated by the mesenchymal/epithelial interactions.

Expression pattern of Irx1 and Irx2 during mouse digit development.

Irx1 and Irx2 are members of the murine Iroquois homeobox (Irx) gene family. In this study, we describe the dynamic expression pattern of these genes during limb development with a focus on digit formation. We further present a comparative expression analysis with Gli genes (Gli1, Gli2, Gli3). Gli1, Gli2, and Gli3 were suggested for candidate regulators of the Irx genes. The expression was studied between E11.5 and E14.5 when the digits are being formed. Irx1 and Irx2 reproduce the developmental program of the digits in time and space and the Irx1 provides an early and excellent marker for this process. Our analysis also indicates that the expression of Irx1, Gli1 and Irx2, Gli2 are relative to each other. In contrast, Gli3 exhibits a different expression pattern.

Vibration perception threshold testing in patients with diabetic neuropathy: ceiling effects and reliability.

AIMS: To test the reliability of a new vibrometer (Maxivibrometer) which was constructed so that vibration perception threshold (VPT) could be determined without the disadvantage of the off-scale measurements frequently experienced with the Biothesiometer. METHODS: The two devices were compared and tested on a group of diabetic neuropathic subjects and a group of healthy, matched control subjects. VPT was tested on the plantar surface of the feet. RESULTS: The Maxivibrometer gave an actual measurement in all cases even if subjects were severely neuropathic. The replication-to-replication and day-to-day intraclass correlation coefficients for the Maxivibrometer VPT were, except in one case, above 0.94, indicating excellent reliability. The Biothesiometer VPT could also be measured with excellent reliability but only within a limited range of mild to moderate neuropathy, so it appears to be an appropriate screening tool. The replication-to-replication intraclass correlation coefficient was 0.93. CONCLUSIONS: Because VPT could be measured over a wide range with the Maxivibrometer, it was demonstrated that loss of sensation in diabetic neuropathy can progress far beyond the maximum VPT value of the Biothesiometer. The wide measurement range and the excellent reliability make the Maxivibrometer a valuable research tool to quantify loss of sensation, particularly in the presence of severe neuropathy and to record changes over time. Diabet. Med. 18, 469-475 (2001)

The novel transcription factor gene Sp5 exhibits a dynamic and highly restricted expression pattern during mouse embryogenesis.

We describe the sequence and expression pattern of Sp5, a novel member of the vertebrate Sp1 transcription factor gene family which consists of at least five members. This gene family is characterized by a highly conserved domain which is formed by three Zn fingers, which bind to the GC box or the GT/CACC box in the promoter of many genes. These boxes are important cis-acting elements required for the expression of the respective genes. In vitro experiments indicate that the Sp1 transcription factors act by influencing the methylation state of the DNA, or by direct interactions with other promoter specific transcription factors. Despite intensive research, the results from in vivo experiments, including targeted gene inactivation, have been difficult to explain. This may be due to possible redundancies and interferences with other transcription factors of this gene family. Here, we report the isolation of the mouse Sp5 gene, a novel Sp1 homolog. Its sequence indicates that Sp5 is a possible link between Sp1 and the closely related BTEB/KLF gene family. We provide detailed information of its highly dynamic expression pattern during mouse embryogenesis in the developing brain, the spinal cord, the trigeminal ganglia, the somites and additional sites outside the nervous system starting from embryonic day 7.25 (E7.25) up to E10.5.

Design criteria for rigid rocker shoes.

In this study nine different rigid rocker shoe designs were tested in 17 symptom-free male subjects and compared with the control condition of a flexible, non-rockered extra-depth shoe with the same flat insole. Effects of both rocker height and axis location were explored. Peak pressure was reduced at most forefoot locations by rocker shoes, but increased in the midfoot and heel. Axis location was found to have an important effect, particularly on hallux pressures. On average the best axis location for reducing metatarsal head (MTH) pressure was in the region of 55-60% of shoe length, while for the toes it was 65%. There was a mean trend towards optimal reduction of pressure in one of the rocker shoe conditions at each anatomical location, but the axis position for this optimal placement was variable across subjects and anatomical locations. While most configurations of the rocker shoes were superior to the control shoe, no single configuration was optimal for all subjects at all sites or even for all subjects at the same site. Therefore, some form of plantar pressure measurement in conjunction with gait training to ensure correct use of the rocker shoes would appear to be essential if the pressure reducing effect of the rigid rocker bottom shoe is to be optimized.

Neuropathic gait shows only trends towards increased variability of sagittal plane kinematics during treadmill locomotion.

Patients with diabetes mellitus (DM) and peripheral neuropathy (PN) are at greater risk of falling and of suffering injuries during falls. It has been hypothesized that PN leads to changes in gait variability that may account for this increased risk. The purpose of this investigation was to analyze the variability of the sagittal plane kinematics of diabetic neuropathic (NP), diabetic non-neuropathic (NNP) and age- and weight-matched control subjects (Control) during motorized treadmill walking at constant speed. While there were distinct trends towards increased variability within the three diagnostic groups (NP > NNP > Control) for several measures of gait variability, most of these trends were not statistically significant. We hypothesize that motorized treadmill walking may be inherently less variable than overground walking and that statistical measures of variability may not be sufficient to fully characterize stride-to-stride variability in human locomotion.

Identification of the vertebrate Iroquois homeobox gene family with overlapping expression during early development of the nervous system.

In Drosophila the decision processes between the neural and epidermal fate for equipotent ectodermal cells depend on the activity of proneural genes. Members of the Drosophila Iroquois-Complex (Iro-C) positively regulate the activity of certain proneural AS-C genes during the formation of external sensory organs. We have identified and characterized three mouse Iroquois-related genes: Irx1, -2 and -3, which have a homeodomain very similar to that of the Drosophila Iro-C genes. The sequence similarity implies that these three genes represent a separate homeobox family. All three genes are expressed with distinct spatio/temporal patterns during early mouse embryogenesis. These patterns implicate them in a number of embryonic developmental processes: the A/P and D/V patterning of specific regions of the central nervous system (CNS), and regionalization of the otic vesicle, branchial epithelium and limbs.

The mechanism of plantar unloading in total contact casts: implications for design and clinical use.

Although the total contact cast (TCC) has been shown to be an extremely effective treatment for the healing of plantar ulcers in diabetic patients, little is known about the biomechanics of its action. In this study, plantar pressure and ground reaction force measurements were obtained from over 750 foot contacts as five subjects with known elevated plantar forefoot pressures walked barefoot, in a padded cast shoe, and a TCC. Peak plantar pressures in the forefoot were markedly reduced in the cast compared with both barefoot and shoe walking (reductions of 75% and 86% respectively, P < 0.05). Peak plantar pressures in the heel were not, however, significantly different between the shoe and the TCC, and the longer duration of heel loading resulted in an impulse that was more than twice as great in the cast compared with the shoe (P < 0.05). An analysis of load distribution indicated that the mechanisms by which the TCC achieves forefoot unloading are (1) transfer of approximately 30% of the load from the leg directly to the cast wall, (2) greater proportionate load sharing by the heel, and (3) removal of a load-bearing surface from the metatarsal heads because of the "cavity" created by the soft foam covering the forefoot. These results point out some of the "essential design features" of the TCC (which are different from what had been previously supposed), support the use of the TCC for healing plantar ulcers in the forefoot, but raise questions about its utility in the healing of plantar ulcers on the heel.

Diabetic sensory neuropathy effect on ankle joint movement perception.

OBJECTIVE: To determine if diabetic subjects with lower extremity cutaneous sensory neuropathy also have a loss of ankle joint movement perception. The strength of association between measurements of ankle joint movement perception and measures of cutaneous sensory function was also investigated. DESIGN: Diabetic subjects with and without sensory neuropathy and individuals without diabetes participated in this study. SETTING: All subjects were community-living individuals. PARTICIPANTS: Fifty-one subjects, ages 40 to 68. Seventeen of the 34 subjects with diabetes had significant distal sensory neuropathy as determined by cutaneous perception of mechanical vibration. All individuals without diabetes were volunteers from the community. Most subjects with diabetes were recruited through direct referral from their physicians. INTERVENTIONS: Ankle joint movement perception threshold (JMPT) was assessed using a device designed for this study. Cutaneous sensory function under both halluces was measured for vibration perception using a vibrometer and for touch-pressure perception using Semmes-Weinstein monofilaments. MAIN OUTCOME MEASURES: Ankle JMPTs (degrees) were compared to measurements of cutaneous vibration perception (volts) and touch-pressure perception (monofilaments force ratings). RESULTS: Diabetic subjects with cutaneous sensory neuropathy demonstrated a significant loss of ankle movement perception (p < .01). Correlation between JMPT and cutaneous sensory tests ranged from Spearman's rank r = .43 to .67. CONCLUSIONS: Although individuals with cutaneous sensory loss secondary to diabetic neuropathy also demonstrated loss of movement perception at the ankle, the relatively low explained variance between the two types of assessment (18% to 45%) indicates that the severity of ankle joint movement perception deficits cannot be directly implied from cutaneous sensory tests.

Foot function in diabetic patients after partial amputation.

The function of partially amputated feet in 10 patients with diabetes mellitus was studied. First-step bilateral barefoot plantar pressure distribution and three-dimensional kinematic data were collected using a Novel EMED platform and three video cameras. Analysis of the plantar pressure data revealed a significantly greater mean peak plantar pressure in the feet with transmetatarsal amputation (TMA) than in the intact feet of the same patients. The heels of the amputated feet had significantly lower mean peak plantar pressures than all the forefoot regions. A significantly greater maximum dynamic dorsiflexion range of motion was seen in the intact compared with the TMA feet. However, no difference was noted in the static dorsiflexion range of motion between the two feet and there was, therefore, a trend for the TMA feet to use less of the available range of motion. Given the altered kinematics and elevated plantar pressures noted in this study, careful postsurgical footwear management of feet with TMA would appear to be essential if ulceration is to be prevented.

Postural instability in patients with diabetic sensory neuropathy.

OBJECTIVE: Recent survey evidence suggests that sensory ataxia due to diabetic neuropathy may be a more frequent and serious problem than is commonly recognized. This view is further supported by research that confirms the major contribution of the somatosensory system to the control of posture. We therefore sought to determine the effects of significant diabetic distal symmetrical polyneuropathy on the control of posture. RESEARCH DESIGN AND METHODS: Fifty-one subjects, divided into three groups, participated in this study. Seventeen had diabetes and significant sensory neuropathy, 17 had diabetes and no neuropathy, and 17 had neither diabetes nor neuropathy. The subjects were matched across groups, and stringent exclusion criteria were applied. Postural stability during quiet standing was measured using a force platform. In addition to electrophysiological and quantitative sensory tests of neuropathy, a number of physical and functional characteristics were measured for all subjects. RESULTS: Postural instability was found to be significantly associated with sensory neuropathy, but not with diabetes per se. Patients with sensory neuropathy demonstrated between 66 and 117% more instability than did control subjects (depending on the testing condition). Based on multiple linear regression analyses, the most significant correlates of instability were the quantitative sensory measures of neuropathy and age. CONCLUSIONS: The loss of sensory perception secondary to diabetic distal symmetrical sensory neuropathy has a markedly detrimental effect on postural stability. The deficit is greatest when visual or vestibular cues are absent or degraded. Patients with neuropathy need to be informed of the postural consequences of this condition to limit the potential morbidity caused by falls.