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PubMed1991

Time of the deepest root for polymorphism in human mitochondrial DNA.

A molecular clock analysis was carried out on the nucleotide sequences of parts of the major noncoding region of mitochondrial DNA (mtDNA) from the major geographic populations of humans. Dates of branchings in the mtDNA tree among humans were estimated with an improved maximum likelihood method. Two species of chimpanzees were used as an outgroup, and the mtDNA clock was calibrated by assuming that the chimpanzee/human split occurred 4 million years ago, following our earlier works. A model of homogeneous evolution among sites does not fit well with the data even within hypervariable segments, and hence an additional parameter that represents a proportion of variable sites was introduced. Taking account of this heterogeneity among sites, the date for the deepest root of the mtDNA tree among humans was estimated to be 280,000 +/- 50,000 years old (+/- 1 SE), although there remains uncertainty about the constancy of the evolutionary rate among lineages. The evolutionary rate of the most rapidly evolving sites in mtDNA was estimated to be more than 100 times greater than that of a nuclear pseudogene.

Animals↗

PubMed2002

An EGS4 based Monte Carlo code for the calculation of organ equivalent dose to a modified Yale voxel phantom.

Organ or tissue equivalent dose, the most important quantity in radiation protection, cannot be measured directly. Therefore it became common practice to calculate the quantity of interest with Monte Carlo methods applied to so-called human phantoms, which are virtual representations of the human body. The Monte Carlo computer code determines conversion coefficients, which are ratios between organ or tissue equivalent dose and measurable quantities. Conversion coefficients have been published by the ICRP (Report No. 74) for various types of radiation, energies and fields, which have been calculated, among others, with the mathematical phantoms ADAM and EVA. Since then progress of image processing, and of clock speed and memory capacity of computers made it possible to create so-called voxel phantoms, which are a far more realistic representation of the human body. Voxel (Volume pixel) phantoms are built from segmented CT and/or MRI images of real persons. A complete set of such images can be joined to a 3-dimensional representation of the human body, which can be linked to a Monte Carlo code allowing for particle transport calculations. A modified version of the VOX_TISS8 human voxel phantom (Yale University) has been connected to the EGS4 Monte Carlo code. The paper explains the modifications, which have been made, the method of coupling the voxel phantom with the code, and presents results as conversion coefficients between organ equivalent dose and kerma in air for external photon radiation. A comparison of the results with published data shows good agreement.

Adult↗

PubMed2006

The reorganization of tremulous movements in the upper limb due to finger tracking maneuvers.

In light of the interplay between limb oscillatory outputs and the outcome performance of movement effectors, this study was undertaken to investigate neuromotor control in the upper limb during position tracking and posture holding. Sixteen volunteers conducted a postural pointing task and two index tracking maneuvers at 0.3 and 0.6 Hz with an outstretched arm. Limb acceleration in the index finger, hand, forearm, arm, and C7 spinal process were monitored to correlate functionally with the accuracy of index rhythmic displacements. The results showed that index oscillatory activity multiplied with tracking speed, but hand oscillatory activity declined during tracking movement. The tracking maneuvers also altered spectral distribution of the tremulous activities in the context of a lower spectral peak in the range of 8-12 Hz and suppression of spectral peaks at 2-4 Hz, in reference to that already presented in posture tremor. Consisting of three local maxima around 2-4, 8-12, and 18-22 Hz, the coherence of tremulous activity between the finger and hand during position tracking was nearly identical, but inferior to high coherence below 12 Hz during posture holding. Functionally, better tracking performance was associated with a smaller tremulous activity in the finger and hand, entailing sophisticated release of mechanical couplings in the finger-hand and hand-forearm. In conclusion, inversely related to tracking performance, limb tremulous movements were task-dependently organized, and speed-invariant coherence of limb tremulous movement specified an inter-segmental coordination, which is physiological evidence of the generalized motor program for position tracking.

Adult↗

PubMed2002

Electrophysiologic identification of the location of the colonic pacemakers. A human study.

Colonic inertia, total or segmental, is a known cause of constipation, yet its etiology is poorly understood and its treatment not satisfactory. Although the colonic electric activity has been studied by many investigators, the colonic pacemakers that are assumed to generate the electric waves, are scarcely addressed and their location, to our knowledge, has not been determined. The current communication investigates the possible sites of the colonic pacemakers, aiming at a better understanding of the mechanism of colonic motility and its disorders, notably colonic inertia. The tests were performed during the repair of huge incisional hernia in 12 subjects (mean age 37.7 +/- 10.2 years, 7 women). Monopolar silver-silver chloride electrodes were applied to the terminal ileum (TI) and cecum (C), and to the ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC); they were fixed by electrode gel to the ileal and colonic serosa. The electric activity of each of the TI, C, AC, TC, DC and SC was recorded. Electric waves in the form of slow waves or pacesetter potentials and action potentials were recorded from the TI and colon. Differences in the frequency, amplitude and conduction velocity of the waves occurred between the TI and the various segments of the colon. The change in the wave variables between the TI and C occurred at the ileocecal junction, between the C and AC at the cecocolonic junction, the AC and TC at the mid third of the TC and the DC and SC at the colosigmoid junction. The colonic electric waves are suggested to be generated by at least 4 pacemakers, which are presumably located at the ileocecal junction, the cecocolonic junction, the mid third of TC and at the colosigmoid junction. The electric waves appear to be responsible for conducting the colonic motor activity. We postulate that disordered colonic pacemakers may produce segmental or total colonic inertia, a proposition that needs further investigation.

Action Potentials↗

PubMed1994

Diamond flap anoplasty in infants and children with an intractable anal stricture.

After posterior sagittal anorectoplasty for imperforate anus a prolonged course of anal dilatations is necessary until the scar softens. Although rare, severe stricture after this procedure is difficult to resolve. Y-V plasty is not entirely satisfactory because the pedicle advanced into the anus has some tension, which tends to retract producing recurrent stricture. The authors performed a diamond-shaped island anoplasty in eight children with postoperative and strictures (one after an unsuccessful Y-V plasty), with prompt resolution of the stricture in five. The island flap anoplasty consists of a diamond-shaped flap of skin formed laterally, with complete separation of skin and subcutaneous attachments around the periphery of the flap. The skin island is supplied with blood from the deep tissue. An incision is made through the scarred anal ring and into the mucosa, a distance of half the length of the diamond, which is then advanced into the mucosal defect. The defect lateral to the advanced flap is sutured closed. The island of skin descends naturally into the anus, under no tension. The procedure can be performed simultaneously in the 3 o'clock and 9 o'clock positions, and can later be repeated anteriorly and posteriorly, although this has not been necessary. Two of the eight children have required no dilatation postoperatively, a distinct advantage in the 4-year-old patient. One segment in one child sloughed, resulting in repeat stricture that is responding to dilatation. The other seven children are doing well with their colostomies closed.

Anus, Imperforate↗

PubMed1988

Analysis of higher-primate phylogeny from transversion differences in nuclear and mitochondrial DNA by Lake's methods of evolutionary parsimony and operator metrics.

In the companion paper (Holmquist et al. 1988), we concluded that there is no agreement on either the correct branching order or differential rates of evolution among the higher primates, and we examined in depth why this uncertainty in the evolutionary understanding of our closest living relatives persists. Recently, Lake developed two novel methods, based on group properties of transition and transversion operators, that (a) permit, in principle, objective resolution of problems of the above type and (b) attach a statistical significance level to the conclusions drawn. In the present paper, we develop formulas for using these two methods in tandem and apply them to study transversion differences in (1) nuclear DNA for a 7-kb segment of the psi eta-globin locus and a 3-kb intergenic region between the psi beta- and delta-globin loci and (2) mitochondrial DNA for the 896-bp fragment of Brown et al. Although each of these nucleotide sequence regions has its characteristic tempo and mode of evolution, the nuclear and mitochondrial data together, comprising a total of 10,939 base positions, support a Homo/Pan clade at the 97% confidence level. If we calibrate the divergence point for humans and chimpanzees at 5 Myr, consideration of the transversion branch lengths for the combined nuclear data indicates that the gorilla lineage branched off 600,000-900,000 years prior to that, although the 2 sigma sampling errors do not preclude either a temporal trifurcation for the three species or a considerably more ancient branch point for the gorilla. To resolve the length of this central branch to a relative accuracy of 25% and 30% will require a factor of 16 and nine times more data, respectively--i.e., in excess of 100,000 homologous nucleotides for each of the four primates. For the nuclear genes, heterogeneity in evolutionary rates between different parts of the genome is mostly restricted to the human lineage for these two segments. The lineage leading to chimpanzees has evolved 0.4 (3-kb fragment) to 3.5 (7-kb segment) times as rapidly as the lineage leading to humans, and that leading to the gorilla has evolved approximately one-fifth to one-half as rapidly as that leading to chimpanzees. Thus, even local molecular clocks can "tick" badly. As significant is the fact that virtually contiguous parts of the genome tick at markedly different rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

The tau mutation shortens the period of rhythmic photoreceptor outer segment disk shedding in the hamster.

The outer segments of vertebrate retinal photoreceptors undergo periodic shedding of membrane from their distal tips. This circadian rhythm of disk shedding persists with a period of about 24 h in the absence of external time cues. A circadian oscillator controlling photoreceptor disk shedding may exist in the eye, but in addition, the circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) may also influence ocular rhythms including that of disk shedding. The tau mutation directly affects the SCN, and shortens the period of locomotor activity from 24 h in wild-type hamsters to 20 h in homozygous mutants. Here we show that homozygous tau-mutant hamsters in a 20-h light/dark cycle exhibit a 20-h oscillation in the rate of disk shedding, with peak phagosome numbers in the retinal pigmented epithelium occurring just after light onset. The numbers of phagosomes are significantly elevated from mid-dark levels prior to light onset, indicating that the disk shedding cycle anticipates dawn. Under conditions of constant darkness, the disk shedding rhythm in tau-mutant hamsters persists with a period of approximately 20 h. These results indicate that a rhythm of retinal photoreceptor outer segment disk shedding exists in the hamster eye, and that the period of this rhythm is shortened by the tau mutation.

Adaptation, Ocular↗

PubMed1998

Somitogenesis: segmenting a vertebrate.

The partitioning of the vertebrate body into a repetitive series of segments, or somites, requires the spatially and temporally co-ordinated behaviour of mesodermal cells. To date, it remains unknown how applicable our knowledge of the genetic mechanisms governing Drosophila segmentation will be to that of vertebrates, though recent results indicate some degree of conservation. Genetic studies in the mouse point to a major role for the Notch-Delta signalling pathway in somite formation. Furthermore, a molecular clock may be 'ticking' in the presomitic mesoderm.

Animals↗

PubMed2005

The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic.

PURPOSE: To estimate the prevalence of posterior embryotoxon (PE) in the general ophthalmic clinic and to identify any features of PE that suggest that it is pathological rather than physiological. METHODS: Over 700 consecutive patients of all ages were examined with the slit lamp during their routine eye clinic appointment. Patients with posterior embryotoxon were invited to return for full ocular examination including keratometry, corneal topography, and gonioscopy. RESULTS: In all, 49 out of 723 patients were found to have PE. This gives a prevalence of 6.8% with an age range of 18 months to 95 years. There was a higher prevalence in the younger age group of 22.5% (age range 18 months to 20 years) compared to 5.9% in the older age range (21-95 years). A total of 29 patients with PE returned for further examination. Six patients had glaucoma (two with Axenfeld's syndrome and one with aniridia), and one had ocular hypertension. In all, 20 patients had bilateral PE on slit-lamp examination, which increased to 24 with gonioscopy. The majority of the PE was seen temporally (97.9%) and limited to a few clock hours. Gonioscopy showed that eight patients with PE had associated inferior pigmentation of schwalbes line. CONCLUSION: This large series found the prevalence of PE the general ophthalmic clinic to be 6.8%. Its presence should prompt careful anterior segment examination, including gonioscopy, to identify any associated abnormalities that may carry a risk of glaucoma. Children should also be assessed for any associated systemic or genetic abnormality.

Abnormalities, Multiple↗

PubMedDate not supplied

Ultrasound biomicroscopic morphometry of the anterior eye segment before and after one drop of pilocarpine.

PURPOSE: To measure anterior eye-segment morphometric data using ultrasound biomicroscopy. This is a new high-frequency, high-resolution ultrasound method enabling the visualisation of the anterior segment of the living eye with magnification similar to a light microscope. METHODS: Thirteen morphometric parameters of the anterior eye segment were measured before and after the application of one drop of pilocarpine in 10 eyes of 5 persons, using a Zeiss-Humphrey Ultrasound Biomicroscope at a frequency of 50 MHz. In each session, 3 morphometric parameters in the central images (corneal thickness, anterior chamber depth, pupillary diameter) were measured 4 times, and 10 parameters in the radial images (scleral thickness, angle-opening distance, trabecular-iris angle, trabecular-ciliary process distance [TCPD], iris thickness, 1, 2 and 3, iris-ciliary process distance, iris-lens contact distance [ILCD], iris elevation) were measured on the 3, 6 and 9 o'clock meridians three times each. RESULTS: Statistically significant changes were noted in the following parameters: pupillary diameter, iris thickness 1 and 2, and TCPD were decreased, while ILCD was increased after pilocarpine. Wide chamber angles showed a tendency to become narrower and narrow ones to become wider after pilocarpine. CONCLUSION: One drop of pilocarpine caused significant changes in the anterior eye segment morphology. Not only the pupillary diameter decreased but iris thickness and trabecular-ciliary process distance were also decreased simultaneously. At the same time the contact surface between the lens and iris increased significantly. Ultrasound biomicroscopy gives new morphometric image information about the anterior eye segment which is not available using conventional gonioscopy or ophthalmic echography.

Administration, Topical↗

PubMed2001

Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age.

The bacterium Helicobacter pylori colonizes the gastric mucosa of half of the human population, resulting in chronic gastritis, ulcers, and cancer. We sequenced ten gene fragments from pairs of strains isolated sequentially at a mean interval of 1.8 years from 26 individuals. Several isolates had acquired small mosaic segments from other H. pylori or point mutations. The maximal mutation rate, the import size, and the frequency of recombination were calculated by using a Bayesian model. The calculations indicate that the last common ancestor of H. pylori existed at least 2,500-11,000 years ago. Imported mosaics have a median size of 417 bp, much smaller than for other bacteria, and recombination occurs frequently (60 imports spanning 25,000 bp per genome per year). Thus, the panmictic population structure of H. pylori results from very frequent recombination during mixed colonization by unrelated strains.

Bayes Theorem↗

PubMed1998

Uncommon electrocardiographic changes corresponding to symptoms during recurrent pulmonary embolism as documented by computed tomography scans.

Electrocardiographic (ECG) findings of pulmonary embolism (PE) include S1Q3T3 pattern, right bundle-branch block, right-axis deviation, and T-wave inversion in medial precordial leads. We report other uncommon ECG changes associated with various symptoms during recurrent PE as documented by computed tomography (CT) scans in a single patients. An 83-year-old woman was admitted with PE secondary to deep venous thrombosis in the left leg. During episodes of chest pain, ECG showed QTc prolongation (480 ms) with new T-wave inversion in leads III, aVF, and V1-V3, and ST-segment depression in leads V5-V6. Despite adequate anticoagulant therapy, recurrent episodes of PE occurred in the hospital. When the patient experienced sudden chest tightness, ECG showed a new S-wave notch in lead V1 and clock-wise rotation with sinus tachycardia. She also experienced transient syncope with hypotension. At this time, ECG showed transient atrioventricular junctional rhythm followed by sinus arrest, and CT scan showed a new massive embolus in the main pulmonary trunk with right ventricular dilatation, as demonstrated by echocardiography. The mechanism responsible for QTc prolongation with ST-T changes, the S-wave notch in lead V1 with clockwise rotation, or atrioventricular junctional rhythm with sinus arrest during PE may be associated with myocardial ischemia, acute right ventricular overload, or vagal reflex, respectively.

Aged↗

PubMedDate not supplied

Free-floating cyst in the anterior chamber: ultrasound biomicroscopic reports.

PURPOSE: To report a free-floating dislodged pigmented cyst in the anterior chamber and to describe the ultrasound biomicroscopic (UBM) features of the lesion. METHODS: Case report. RESULTS: A 26-year-old man presented with noise in his left eye in the prone position. Slit-lamp examination revealed a small pigmented mass lesion at the 6 o'clock position in the anterior chamber, slowly moving with changing head postures. UBM revealed an unfixed dislodged pigmented cyst with a thin wall and no internal reflectivity, changing its shape from ovoid to circular. Five years later, the anterior segment does not show any modification and the cyst has not changed in size or appearance. CONCLUSIONS: Cysts of the iris pigment epithelium arise in the posterior iris layer. They may be central, midzonal, peripheral, or dislodged. Dislodged cysts may be repositioned and fixed or free-floating in the vitreous or in the anterior chamber. Surgical removal must be considered only for a rapid enlargement or significant reduction in endothelial cell count. UBM can distinguish solid from cystic lesions, giving detailed information on internal structure, reflectivity, shape, and thickness.

Adult↗

PubMed1995

Isolation of timeless by PER protein interaction: defective interaction between timeless protein and long-period mutant PERL.

The period (per) gene likely encodes a component of the Drosophila circadian clock. Circadian oscillations in the abundance of per messenger RNA and per protein (PER) are thought to arise from negative feedback control of per gene transcription by PER. A recently identified second clock locus, timeless (tim), apparently regulates entry of PER into the nucleus. Reported here are the cloning of complementary DNAs derived from the tim gene in a two-hybrid screen for PER-interacting proteins and the demonstration of a physical interaction between the tim protein (TIM) and PER in vitro. A restricted segment of TIM binds directly to a part of the PER dimerization domain PAS. PERL, a mutation that causes a temperature-sensitive lengthening of circadian period and a temperature-sensitive delay in PER nuclear entry, exhibits a temperature-sensitive defect in binding to TIM. These results suggest that the interaction between TIM and PER determines the timing of PER nuclear entry and therefore the duration of part of the circadian cycle.

Animals↗

PubMed1989

Silicone oil in the aphakic eye: the influence of a six o'clock peripheral iridectomy.

Complications after six months, in a series of 44 aphakic eyes treated by vitrectomy and fluid/silicone-oil exchange with six o'clock (Ando) peripheral iridectomy, are reported. Comparisons are made with the complications after six months in a similar series treated prior to the introduction of the six o'clock iridectomy. It is concluded that a patent six o'clock iridectomy is effective in reducing the complications of intraocular silicone oil in the aphakic eye.

Adolescent↗

PubMedDate not supplied

Sunlight and cortical cataract.

We undertook a prospective clinical study to test our initial impression that cortical opacities are seldom present in the upper part of the lens. Data analysis revealed that of 174 eyes having cortical opacities, only 15 (8.62%) had opacities in the area of the lens between the 10- and 2-o'clock positions. Lid retraction, defined as upper lid position at or above the limbus, was seen in 13 (88.66%) of these eyes. Our study indicates that in the absence of lid retraction, cortical opacities are very rarely seen in the upper segment of the lens, a segment that is normally covered by the upper lid. This suggests a protective effect of the upper lid against cortical opacities, and indirectly it supports the theory that senile cortical opacities may be the result of thermal damage to the lens.

Adult↗

PubMed1999

Heat shock produces periodic somitic disturbances in the zebrafish embryo.

Environmental influences are known to produce segmental defects in a variety of organisms. In this paper we report upon segmental aberrations produced by brief heat shocks delivered to developing zebrafish embryos. The initial defects in the segmental pattern of somitic boundaries and motoneuron axon outgrowth were usually observed five somites caudal to the somite which was forming at the time of heat shock application. Segmental defects in zebrafish embryos exposed to a single heat shock treatment can occur in a periodic pattern similar to the multiple disturbances observed to occur in chick embryos. These data are discussed with regard to models involving cell cycle synchrony or 'clock and wavefront' schemes in the process of somitogenesis.

Animals↗

PubMed2004

Blood pressure lability and glomerulosclerosis after normotensive 5/6 renal mass reduction in the rat.

BACKGROUND: Hypertension plays a major role in the progression of both experimental and clinical chronic renal disease. However, the pathogenesis of the more slowly developing glomerulosclerosis that is seen even in the absence of overt hypertension, both in renal mass reduction models and in humans with chronic renal disease, remains controversial. METHODS: The relationship of such glomerulosclerosis to the ambient blood pressure profiles was examined in the normotensive approximately 5/6 surgical excision rat remnant kidney model. Blood pressure was radiotelemetrically monitored at 10-minute intervals for 15 to 16 weeks ( approximately 15,000 blood pressure readings) in untreated rats (N= 13), or those treated with enalapril (N= 8), amlodipine (N= 9), or a combination of hydralazine, reserpine, and hydrochlorothiazide (N= 10). RESULTS: Even in these normotensive rats (systolic blood pressure <140 mm Hg), % glomerulosclerosis was significantly correlated with the overall average systolic blood pressure (r= 0.62, P < 0.0001; N= 40). However, much stronger correlations were observed between glomerulosclerosis and the % systolic blood pressure readings >150 mm Hg (r= 0.77, P < 0.0001) and the standard deviation of the average systolic blood pressure (r= 0.87, P < 0.0001). CONCLUSION: These data indicate that pressure dependent injury mechanisms continue to contribute to glomerular injury even within the "normotensive" blood pressure range in rats with reduced renal mass. This most likely represents the consequence of the impairment of protective renal autoregulation and enhanced glomerular transmission of the blood pressure fluctuations into the hypertensive range characteristic of the conscious state in both experimental animals and in humans. Such pathophysiology supports the need for more aggressive and around-the-clock blood pressure control in chronic renal disease.

Animals↗