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PubMedDate not supplied

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-beta superfamily.

Predictable bone induction in clinical contexts requires information on the expression and cross regulation of gene products of the transforming growth factor-beta (TGF-beta) superfamily elicited by single applications of each recombinant human bone morphogenetic/osteogenic proteins (BMPs/OPs). Using the calvarium and the rectus abdominis muscle of adult baboons Papio ursinus as a model for tissue induction and morphogenesis, this study investigated the induction of bone morphogenesis by gamma-irradiated hOP-1 delivered by gamma-irradiated bovine insoluble collagenous bone matrix, the hOP-1 osteogenic device, for bone induction in heterotopic and orthotopic sites of the primate Papio ursinus and the expression patterns of OP-1, collagen type IV, BMP-3 and TGFbeta1mRNAs elicited by increasing single applications of doses of the hOP-1 osteogenic devices (0.1, 0.5 and 2.5 mg hOP-1/g of matrix) applied heterotopically in the rectus abdominis muscle and orthotopically in 48 calvarial defects of 12 adult baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 15, 30 and 90 showed that all the doses of the hOP-1 osteogenic device induced bone formation culminating in complete calvarial regeneration by day 90. Type IV collagen mRNA expression, a marker of angiogenesis, was strongly expressed in both heterotopic and orthotopic tissues. High levels of expression of OP-1 mRNA demonstrated autoinduction of OP-1 mRNAs. Expression levels of BMP-3 mRNA varied from tissues induced in heterotopic vs. orthotopic sites with high expression in rapidly forming heterotopic ossicles together with high expression of type IV collagen mRNA. The temporal and spatial expressions of TGF-beta1 mRNAindicate a specific temporal transcriptional window during which expression of TGF-beta1 is mandatory for successful and optimal osteogenesis. The induction of bone by hOP-1 in Papio ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF-beta superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis.

Animals↗
PubMed2006

Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression.

Hop is an unusual homeodomain protein that was first identified in the developing heart where it functions downstream of Nkx2.5 to modulate cardiac gene expression. Hop functions through interactions with histone deacetylase (HDAC) 2 to mediate repression of cardiac-specific genes, and recent studies show that HDAC activity and HDAC2 expression are decreased in people with chronic obstructive pulmonary disease. Here, we show that Hop is expressed in airway epithelium coincident with HDAC2, and expression is induced by the combination of dexamethasone and cAMP in parallel with induction of surfactant protein gene expression. Hop functions in the developing pulmonary airway, acting downstream of Nkx2.1 and GATA6, to negatively regulate surfactant protein expression. Loss of Hop expression in vivo results in defective type 2 pneumocyte development with increased surfactant production and disrupted alveolar formation. Thus Hop represents a novel regulator of pulmonary maturation that is induced by glucocorticoids to mediate functionally important HDAC-dependent negative feedback regulation.

Animals↗
PubMed1991

Hopping frequency in humans: a test of how springs set stride frequency in bouncing gaits.

The storage and recovery of elastic energy in muscle-tendon springs is important in running, hopping, trotting, and galloping. We hypothesized that animals select the stride frequency at which they behave most like simple spring-mass systems. If higher or lower frequencies are used, they will not behave like simple spring-mass systems, and the storage and recovery of elastic energy will be reduced. We tested the hypothesis by having humans hop forward on a treadmill over a range of speeds and hop in place over a range of frequencies. The body was modeled as a simple spring-mass system, and the properties of the spring were measured by use of a force platform. Our subjects used nearly the same frequency (the "preferred frequency," 2.2 hops/s) when they hopped forward on a treadmill and when they hopped in place. At this frequency, the body behaved like a simple spring-mass system. Contrary to our predictions, it also behaved like a simple spring-mass system when the subjects hopped at higher frequencies, up to the maximum they could achieve. However, at the higher frequencies, the time available to apply force to the ground (the ground contact time) was shorter, perhaps resulting in a higher cost of generating muscular force. At frequencies below the preferred frequency, as predicted by the hypothesis, the body did not behave in a springlike manner, and it appeared likely that the storage and recovery of elastic energy was reduced. The combination of springlike behavior and a long ground contact time at the preferred frequency should minimize the cost of generating muscular force.

Adult↗
PubMed2005

Homeobox protein Hop functions in the adult cardiac conduction system.

Hop is an unusual homeobox gene expressed in the embryonic and adult heart. Hop acts downstream of Nkx2-5 during development, and Nkx2-5 mutations are associated with cardiac conduction system (CCS) defects. Inactivation of Hop in the mouse is lethal in half of the expected null embryos. Here, we show that Hop is expressed strongly in the adult CCS. Hop-/- adult mice display conduction defects below the atrioventricular node (AVN) as determined by invasive electrophysiological testing. These defects are associated with decreased expression of connexin40. Our results suggest that Hop functions in the adult CCS and demonstrate conservation of molecular hierarchies between embryonic myocardium and the specialized conduction tissue of the mature heart.

Animals↗
PubMed2003

Cardiac hypertrophy and histone deacetylase-dependent transcriptional repression mediated by the atypical homeodomain protein Hop.

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. Repression of antihypertrophic pathways has rarely been demonstrated to cause cardiac hypertrophy in vivo. Hop is an unusual homeodomain protein that is expressed by embryonic and postnatal cardiac myocytes. Unlike other homeodomain proteins, Hop does not bind DNA. Rather, it modulates cardiac growth and proliferation by inhibiting the transcriptional activity of serum response factor (SRF) in cardiomyocytes. Here we show that Hop can inhibit SRF-dependent transcriptional activation by recruiting histone deacetylase (HDAC) activity and can form a complex that includes HDAC2. Transgenic mice that overexpress Hop develop severe cardiac hypertrophy, cardiac fibrosis, and premature death. A mutant form of Hop, which does not recruit HDAC activity, does not induce hypertrophy. Treatment of Hop transgenic mice with trichostatin A, an HDAC inhibitor, prevents hypertrophy. In addition, trichostatin A also attenuates hypertrophy induced by infusion of isoproterenol. Thus, chromatin remodeling and repression of otherwise active transcriptional processes can result in hypertrophy and heart failure, and this process can be blocked with chemical HDAC inhibitors.

Animals↗
PubMedDate not supplied

Abnormal lower limb symmetry determined by function hop tests after anterior cruciate ligament rupture.

This study assessed the sensitivity of four different types of one-legged hop tests. The goal was to determine alterations in lower limb function in ACL deficient knees. Regression analyses were conducted between limb symmetry as measured by the hop tests and muscle strength, symptoms, and self-assessed function. In 67 patients, 50% had abnormal limb symmetry scores on a single hop test. When the results of two hop tests were calculated, the percent of abnormal scores increased to 62%. The percentage of normal scores indicated that these hop tests had a low sensitivity rate. However, the high specificity and low false-positive rates allow the tests to be used to confirm suspected defects in lower limb function. Statistical trends were noted between abnormal limb symmetry on the hop tests and low velocity quadriceps isokinetic test results.

Adolescent↗
PubMed1987

Differential effects of pinealectomy on circadian rhythms of feeding and perch hopping in the European starling.

To study the effects of pinealectomy on the circadian rhythms of locomotor activity and feeding. European starlings (Sturnus vulgaris) were held in constant light (0.2 lux and 200 lux) and under constant temperature conditions. Locomotor activity was measured by means of perches with microswitches mounted underneath, and feeding with an infrared photocell system at the feeder. Pinealectomy consistently led to disturbances in perch-hopping rhythms and often to a complete loss of rhythmicity as revealed by periodogram analysis. In some birds, perch-hopping rhythms recovered following a period of initial arrhythmicity. When a perch-hopping rhythm was present, its period was usually shorter than it had been before pinealectomy. In contrast to its effects on perch hopping, pinealectomy had no effect on the persistence of feeding rhythmicity, although its period, like that of the hopping rhythm, decreased after this operation. These results support the hypothesis derived from previous studies that the circadian organization of feeding is different from that of perch hopping. Different circadian pacemakers may be involved, but other models may possibly explain the data just as well.

Animals↗
PubMed1999

Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer.

The female flowers of the hop plant are used as a preservative and as a flavoring agent in beer. However, a recurring suggestion has been that hops have a powerful estrogenic activity and that beer may also be estrogenic. In this study, sensitive and specific in vitro bioassays for estrogens were used for an activity-guided fractionation of hops via selective solvent extraction and appropriate HPLC separation. We have identified a potent phytoestrogen in hops, 8-prenylnaringenin, which has an activity greater than other established plant estrogens. The estrogenic activity of this compound was reflected in its relative binding affinity to estrogen receptors from rat uteri. The presence of 8-prenylnaringenin in hops may provide an explanation for the accounts of menstrual disturbances in female hop workers. This phytoestrogen can also be detected in beer, but the levels are low and should not pose any cause for concern.

Animals↗
PubMed2000

The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids.

The female flowers of the hop plant have long been used as a preservative and a flavoring agent in beer, but they are now being included in some herbal preparations for women for "breast enhancement." This study investigated the relative estrogenic, androgenic and progestogenic activities of the known phytoestrogen, 8-prenylnaringenin, and structurally related hop flavonoids. 6-Prenylnaringenin, 6,8-diprenylnaringenin and 8-geranylnaringenin exhibited some estrogenicity, but their potency was less than 1% of that of 8-prenylnaringenin. 8-Prenylnaringenin alone competed strongly with 17ss-estradiol for binding to both the alpha- and ss-estrogen receptors. None of the compounds (xanthohumol, isoxanthohumol, 8-prenyl-naringenin, 6-prenylnaringenin, 3'-geranylchalconaringenin, 6-geranylnaringenin, 8-geranylnaringenin, 4'-O:-methyl-3'-prenylchalconaringenin and 6,8-diprenylnaringenin) nor polyphenolic hop extracts showed progestogenic or androgenic bioactivity. These results indicate that the endocrine properties of hops and hop products are due to the very high estrogenic activity of 8-prenylnaringenin and concern must be expressed about the unrestricted use of hops in herbal preparations for women.

Androgens↗
PubMed2005

HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulation.

The liver has the ability to autonomously regulate growth and mass. Following partial hepatectomy, hormones, growth factors, cytokines and their coupled signal transduction pathways have been implicated in hepatocyte proliferation. To understand the mechanisms responsible for the proliferative response, we studied liver regeneration by characterization of novel genes that are activated in residual hepatocytes. A regenerating liver cDNA library screening was performed with cDNA-subtracted probes derived from regenerating and normal liver. Here, we describe the biology of Hops (for hepatocyte odd protein shuttling). HOPS is a novel shuttling protein that contains an ubiquitin-like domain, a putative NES and a proline-rich region. HOPS is rapidly exported from the nucleus and is overexpressed during liver regeneration. Evidence shows that cAMP governs HOPS export in hepatocytes of normal and regenerating liver and is mediated via CRM-1. We demonstrate that HOPS binds to elongation factor eEF-1A and interferes in protein synthesis. HOPS overexpression in H-35-hepatoma and 3T3-NIH cells strongly reduces proliferation.

Amino Acid Sequence↗
PubMed2004

Dynamics of leg muscle function in tammar wallabies (M. eugenii) during level versus incline hopping.

The goal of our study was to examine whether the in vivo force-length behavior, work and elastic energy savings of distal muscle-tendon units in the legs of tammar wallabies (Macropus eugenii) change during level versus incline hopping. To address this question, we obtained measurements of muscle activation (via electromyography), fascicle strain (via sonomicrometry) and muscle-tendon force (via tendon buckles) from the lateral gastrocnemius (LG) and plantaris (PL) muscles of tammar wallabies trained to hop on a level and an inclined (10 degrees, 17.4% grade) treadmill at two speeds (3.3 m s(-1) and 4.2 m s(-1)). Similar patterns of muscle activation, force and fascicle strain were observed under both level and incline conditions. This also corresponded to similar patterns of limb timing and movement (duty factor, limb contact time and hopping frequency). During both level and incline hopping, the LG and PL exhibited patterns of fascicle stretch and shortening that yielded low levels of net fascicle strain [LG: level, -1.0+/-4.6% (mean +/- S.E.M.) vs incline, 0.6+/-4.5%; PL: level, 0.1+/-1.0% vs incline, 0.4+/-1.6%] and muscle work (LG: level, -8.4+/-8.4 J kg(-1) muscle vs incline, -6.8+/-7.5 J kg(-1) muscle; PL: level, -2.0+/-0.6 J kg(-1) muscle vs incline, -1.4+/-0.7 J kg(-1) muscle). Consequently, neither muscle significantly altered its contractile dynamics to do more work during incline hopping. Whereas electromyographic (EMG) phase, duration and intensity did not differ for the LG, the PL exhibited shorter but more intense periods of activation, together with reduced EMG phase (P<0.01), during incline versus level hopping. Our results indicate that design for spring-like tendon energy savings and economical muscle force generation is key for these two distal muscle-tendon units of the tammar wallaby, and the need to accommodate changes in work associated with level versus incline locomotion is achieved by more proximal muscles of the limb.

Animals↗
PubMed2006

On scaffolds and hopping in medicinal chemistry.

The molecular scaffold is an oft-cited concept in medicinal chemistry suggesting that the definition of what makes a scaffold is rigorous and objective. However, this is far from the case with the definition of a scaffold being highly dependent on the particular viewpoint of a given scientist. It follows, therefore, that the definition of scaffold hopping and, more importantly, the detection of what constitutes a scaffold hop, is also ill-defined and highly subjective. Essentially, it is agreed that scaffolds should be substantially different from each other, although significantly similar to each other, to constitute a hop. In the latter, the scaffolds must permit a similar geometric arrangement of functional groups to permit the mode of action. However, this leaves the paradox of how to describe both scaffold similarity and dissimilarity simultaneously. In this paper, the current statuses of scaffolds and scaffold hopping are reviewed based on published examples of scaffold hopping from the literature. An investigation of the degree to which it is possible to formulate a more rigorous definition of scaffolds and hopping in the context of molecular topologies is considered. These techniques are adapted from chemoinformatics to be applied in the design of new medicinal compounds.

Chemistry, Pharmaceutical↗
PubMed2002

Effect of added mass on human unipedal hopping.

Although hopping is considered a children's activity, it can be used to provide insight into the neuromuscular and biomechanical performance of adults. This study investigated whether mass added during unipedal hopping altered the vertical stiffness, hopping period, and angular kinematics of the lower extremity of adults. Measures of two-dimensional kinematics and vertical force were made from 10 healthy men during hopping at a preferred period under three conditions: Body Mass, Body Mass+10%, and Body Mass+20%. Adding mass significantly increased hopping period and hip flexion without significantly affecting vertical stiffness, ankle dorsiflexion, or knee flexion. Overall, the findings agreed with predictions based on a simple-mass spring model. The results indicate unique kinetic and kinematic responses to increased mass during hopping may have potential application in neuromuscular assessment and training for the lower extremities.

Adolescent↗
PubMed2002

Effect of frequency on human unipedal hopping.

All mature forms of locomotion involve periods of unilateral stance. Unipedal hopping may provide useful information about the neuromuscular and biomechanical capabilities of a single lower extremity in adults. This study investigated whether hopping influenced vertical stiffness and lower extremity angular kinematics during human unipedal hopping. Vertical force and two-dimensional kinematics were measured in 10 healthy males hopping at three frequencies: preferred, +20%, and -20%. At +20%, compared to preferred, vertical stiffness increased 55% as hip flexion, knee flexion, and ankle dorsiflexion decreased, while at -20% vertical stiffness decreased 39.4% as hip flexion, knee flexion, and ankle dorsiflexion increased. As in bipedal hopping, the force-displacement relationship was more springlike at the preferred rate and +20% than at -20%. Given the prevalence of unilateral stance during walking, running, and skipping, findings related to unipedal hopping may be useful in the rehabilitation or conditioning of lower extremities.

Adolescent↗
PubMed2002

One-arm hop test: reliability and effects of arm dominance.

STUDY DESIGN: Test-retest reliability analysis and 2-factor ANOVA contrast of athletic group and limb dominance. OBJECTIVES: To determine the reliability of the one-arm hop test and the effects of upper-extremity dominance on test scores for 2 athletic groups. BACKGROUND: Limited information is available regarding functional performance tests of the upper extremity that involve axial loading. METHODS AND MEASURES: Thirteen male collegiate wrestlers (mean age, 20.3 +/- 1.6 years) and 13 male collegiate football players (mean age, 20.0 +/-1.7 years) without upper-extremity pathology participated in the study. Subjects were trained to perform the one-arm hop test, starting from a one-arm push-up position and then hopping as quickly as possible onto and off of a 10.2-cm platform 5 times. Subjects returned to the test site 1 to 2 days later and were timed for 2 trials of the one-arm hop test for each upper extremity. RESULTS: Within-session ICC2,1 reliability values were 0.78 for the football players and 0.81 for the wrestlers. Mean absolute differences between trials were 0.64 seconds for the football players and 0.47 seconds for the wrestlers. Trial 2 performance times were significantly faster than trial 1 times for the wrestlers. Although performance time for the nondominant side was on average 4.4% slower than that of the dominant side, performance times for the dominant side were not significantly different from those of the nondominant upper extremities. CONCLUSIONS: The results provide preliminary evidence that the one-arm hop test may be a reliable upper-extremity functional performance test with sufficient training of the subject. Uninjured upper-extremity performance for the one-arm hop test may be useful as a basis for comparing performance of an injured contralateral upper extremity.

Adult↗
PubMed2004

Selected parameters of immunological response in hop growers during the period of intensive application of pesticides.

The aim of the study was determination of selected parameters of immunological response among hop growers and farmers in conditions of intensive exposure to means of plant protection. Survey data was collected from 238 males aged 25-70 living in the area of Wilków near Puławy (Lublin Region). Control group were males from the area of Witoszyn (Lublin Region)--53 people aged 25-70 occupied mainly with land cultivation. Based on an environmental survey conducted among hop growers and farmers, the respondents were divided into 3 age groups: 25-40, 41-55 and 56-70. Laboratory tests covered the determination of selected morphological parameters, phagocytic test, NBT test, and myeloperoxidasis (MPO) concentration in blood serum of hop growers and farmers.A significant decrease was noted in the number of platelets in the general population of hop growers and in individual age groups, compared to the control groups of farmers. Analysis of individual sub-populations of leukocytes showed a significantly higher number statistically of basophils and lymphocytes among hop growers, compared to farmers. A detailed analysis of the degree of phagocytic and bactericidal activity of neutrophils allowed us to presume that during the period of spraying there occurred a mobilisation of the granulocytic system, manifested by the presence of over 90% of neutrophils of intensified phagocytic activity, and 20% of neutrophils of intensified bactericidal activity. The preparations prepared by the routine NBT test method were analysed with the use of LUCIA computer programme (version 4.51). The analysis of the level of MPO in blood serum in the populations examined showed the presence of statistically significant differences. In hop growers, the MPO level was significantly higher statistically (60.0 ng/ml), compared to the control group of farmers (43.4 ng/ml).

Adult↗
PubMed1989

Appearance and persistence of 11 beta-hydroxypregna-1,4-diene-3,20-dione (delta HOP) effect "in vivo".

The effect "in vivo" of 11 beta-hydroxy-pregna-1,4-diene-3,20-dione (delta HOP) in acute and chronic treatment was studied in mice compared to those treated with dexamethasone and vehicle. In acute experiments an injection of 2 mg/100 g body weight of delta HOP had a maximal inhibitory effect in 3H-uridine incorporation by thymocytes 18 h after the injection, disappearing 36 h later, meanwhile no change was observed in plasma corticosterone levels at any time. The dose 0.033 mg/100 g body weight of dexamethasone produced a high inhibition 5 h after the injection, and a significant decrease in plasma corticosterone was produced at this time; the effect disappeared at 24 h. In the chronic treatment delta HOP produced the maximal inhibition 5 h after the treatment; this effect was maintained until 36 h and disappeared at 48 h without change in corticosterone levels. Meanwhile dexamethasone produced the same inhibition as delta HOP 5 h after the treatment; this effect disappeared after 18 h. In those animals plasma corticosterone decreased during longer time than in acute treatment, since it continued lower than normal at 18 h and it recovered at 24 h. After 5 h of a chronic treatment delta HOP did not change thymus and spleen weights, but they decreased with dexamethasone treatment. These results suggest that the "in vivo" actions of delta HOP is different from that of glucocorticoids.

Animals↗
PubMed2004

Exposure to bioaerosols: allergic reactions and respiratory function in Polish hop growers.

BACKGROUND: The aim of the study was to assess the prevalence of work-related symptoms in hop growers and their relation to bioaerosols exposure. The study group comprised 69 hop growers and 58 office workers as controls. The examination included: physician-administrated questionnaire, PEF measurements, skin prick test, agar-gel precipitation test, and migration inhibition test. Microbiological air sampling was performed on all farms. RESULTS: The concentrations of total airborne microflora ranged from 2.08 to 129.6 x 10(3) CFU/m3. Airborne endotoxin and dust concentrations ranged from 26 to 6250 ng/m3 and 0.2-31.7 mg/m3, respectively. Altogether 52.2% of farmers complained of work-related symptoms. Positive skin reactions to microbial allergens were significantly more frequent in a group of hop growers with work-related respiratory symptoms compared to the rest of the farmers (18% vs 2%, P <0.05). Positive reactions in agar-gel precipitation test and in the leukocyte migration inhibition test were not correlated with the occurrence of work-related symptoms. The mean daily PEF values in farmers were lower compared to controls (469.7 +/- 127.5 vs 562.9 +/- 123.8; P <0.001). PEF (amp%mean) was higher in farmers compared to controls (9.3% vs 8.1%; P <0.05). CONCLUSION: Despite relatively lower exposure to bioaerosols, compared to farmers in other branches of agriculture, over 50% of hop growers complained of work-related symptoms. This may be partly due to the effects of microbial allergens and toxins and partly to the irritant or allergic properties of hop plant itself.

Adolescent↗