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Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.
The ability of intravenously administered maltose or glucose to supply 12% of the energy requirements of growing miniature pigs was compared. All pigs were fed a stock diet from days 5 to 28 of life, and a central venous catheter was placed at 28 days. For the next 30 days, all pigs were fed orally and intravenously. Positive control pigs were fed the stock diet with infusions of an isotonic balanced electrolyte solution. Negative control and test animals were fed a diet containing cellulose to replace 12% of energy. Negative control animals received the balanced electrolyte solution intravenously, while test animals received either intravenous glucose or maltose at levels providing 12% of energy. Carbohydrate utilization was measured by loss of urinary carbohydrate, as well as by growth and body composition. Chemical analyses of the urine indicated utilization of both maltose and glucose, but maltose was utilized less well (87%) than glucose (greater than 99%). Growth and body composition data also indicate maltose utilization. The data suggest a possible role for maltose infusion as a supplemental energy source.
Yucatan miniature swine have been selected for increased (high K) or decreased (low K) ability to utilize glucose based on an intravenous glucose tolerance test (IVGTT). In this study we tested the effect of obesity in conjunction with ad libitum, high sucrose or high starch diets on IVGTT and the insulin response to glucose in these two lines of animals. Either diet caused increased glucose utilization and an increased insulin response in the low K animals. Neither diet caused a change in these parameters in the high K pigs. There were no differences in either line of animals due to sucrose vs starch diets. During an insulin impedance test both the mean steady state plasma glucose and plasma serum insulin concentration were significantly higher in the high K animals (P less than 0.01).
The effects of short-term starvation (up to 5 days) on hepatic ketone body production was investigated in the conscious unrestrained miniature pig in vivo. Starvation induced an increase in arterial free fatty acid concentration (0.2-0.7 mM) with a concomitant elevation in hepatic free fatty acid extraction [-1.4-5.7 mumol/kg. minute),r = 0.53, P less than 0.005]. Ketone body production (sum of acetoacetate + beta-hydroxybutyrate) increased from 1.5 to 5.8 mumol/(kg . minute) in parallel (r = 0.71, P less than 0.0005). During starvation arterial insulin levels decreased, glucagon increased, cortisol remained unchanged and a "low T3 state' was observed. These data differ in some aspects from those reported for humans and dogs. Thus a species-specific variation in the fuel economy of the pig's body is proposed.
In 21 miniature poodles the 45Ca metabolism was studied at 13, 19 and 25 wk of age. The animals were divided in four groups and fed dry dog food differing only in Ca concentration, i.e., 0.05 (LLC), 0.33 (LC), 1.1 (NC) or 3.3 g/100 g (HC) of Ca on a dry matter basis. The percentage of Ca absorption was significantly higher in the LLC and LC groups (70-96%) than in the NC group (28-53%). True Ca absorption was low and retention almost zero in the LLC dogs, whereas in the HC dogs absorption and retention were more than three times greater than in the NC dogs. The higher retention in the HC group compared with the NC group was primarily the result of a low level of bone removal, the deposition levels being similar in the two groups. We conclude that 1) the 0.33 g/100 g of Ca diet did not meet the minimal requirements for growth in small breed dogs, 2) both low and high dietary Ca caused effects on Ca metabolism similar to those previously observed in giant breed dogs, and 3) small and giant breed dogs require different minimal Ca:energy ratios in the diet during growth.
The mode of transposition of miniature inverted-repeat transposable elements (MITEs) is unknown, but it has been suggested that they are duplicated rather than excised at transposition. However, the present investigation demonstrates that a particular family of MITEs, Stowaway:, is excised. Mapped onto a gene tree based on partial sequences of disrupted meiotic cDNA1 (DMC1) from 30 species of the Triticeae grasses, it is evident that at least two excisions have occurred, leaving short footprints. These footprints may subsequently be reduced in length or deleted. Excision of Stowaway: elements lends strong support to the suggestion that MITEs are DNA transposons and should be classified as class II elements. The evolution of Stowaway: elements can also be traced by scrutiny of the gene tree. It appears that base substitutions are as frequent in the conserved terminal inverted repeats (TIRs) as in the core of the element. Neither substitutions nor deletions lead to compensatory changes; hence, the highly stable secondary structure of the elements may gradually be reduced.
Sequence similarities exist between terminal inverted repeats (TIRs) of some miniature inverted-repeat transposable element (MITE) families isolated from a wide range of organisms, including plants, insects, and humans, and TIRs of DNA transposons from the pogo family. We present here evidence that one of these MITE families, previously described for Arabidopsis thaliana, is derived from a larger element encoding a putative transposase. We have named this novel class II transposon Lemi1. We show that its putative product is related to transposases of the Tc1/mariner superfamily, being closer to the pogo family. A similar truncated element was found in a tomato DNA sequence, indicating an ancient origin and/or horizontal transfer for this family of elements. These results are reminiscent of those recently reported for the human genome, where other members of the pogo family, named Tiggers, are believed to be responsible for the generation of abundant MITE-like elements in an early primate ancestor. These results further suggest that some MITE families, which are highly reiterated in plant, insect, and human genomes, could have arisen from a similar mechanism, implicating pogo-like elements.
A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of PONY: was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they constitute approximately 1. 1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.
The whole cell configuration of the patch clamp technique was used to study the effects of chlorpromazine (CPZ), a widely used antipsychotic drug, on miniature GABAA-mediated synaptic currents (mIPSCs) in hippocampal cells in culture. CPZ (10-30 microM) induced a clear dose-dependent increase of mIPSCs frequency that was associated with a decrease in amplitude and with an acceleration of their decay kinetics. When applied in a calcium-free medium, CPZ was less effective in enhancing mIPSCs frequency, suggesting that this effect was partially calcium dependent. While a low (10 microM) CPZ concentration induced a 2-fold increase in the total charge transfer a higher (30 microM) dose of this drug produced no changes, indicating that the presynaptic effect was counterbalanced by the postsynaptic one.
The origins of spontaneous and noxious stimuli-evoked glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in substantia gelatinosa (SG) neurons were investigated by using whole-cell voltage-clamp technique on adult rat spinal cord slice. The properties of mEPSCs of SG neurons from rats either neonatally capsaicin-treated or sciatic nerve ligated showed no difference from those of intact SG neurons, indicating independence of spontaneous mEPSCs on primary afferent fibers. In the presence of tetrodotoxin (TTX), capsaicin, which noxiously stimulated fine primary afferent fibers, caused increase of the mEPSCs frequency, but did not affect the amplitude profiles or mean amplitudes. TTX affected neither the spontaneous mEPSCs nor capsaicin-induced mEPSCs frequency increase. The results suggest that spontaneous mEPSCs in SG are mediated by presynaptic spontaneous glutamate release predominantly originating from interneuron terminals rather than from primary afferent terminals; under noxious stimulation, however, mEPSCs frequency increase is mediated by primary afferent excitation.
An individual head, auricle, and ear canal can alter signals from a hearing aid other sources of acoustic stimulation compared to artificial couplers. The most realistic method for quantifying or verifying certain parameters of acoustic simulation delivered to the ear by a hearing aid is to measure the sound pressure level of a signal in the ear canal of an individual while wearing an aid. Probe microphone measurements have been conducted and reported for the past 33 years. Until now, such microphone measurements have used a hollow tube inserted into the ear canal which leads to a transducer outside the canal. This paper describes our preliminary clinical application of a new wide range, flat response, miniature electret microphone, measuring 4 x 5 x 2 mm for measurement of insertion gain in a patient's ear canal. We believe the information from these recordings can be useful in developing objective clinical procedures for the selection and monitoring of wearable amplification for hearing-impaired patients.
OBJECTIVE: This report describes the clinical evaluation of a novel stereotactic radiosurgical device for interstitial irradiation of malignant brain tumors. METHODS: Fourteen patients with cerebral lesions less than 3.5 cm in greatest diameter were treated with a single fraction of stereotactic interstitial irradiation (average, 12.5 Gy). Clinical evaluation, Karnofsky Performance Scale ratings, and neuroimaging studies were obtained at 6-week intervals postoperatively to assess treatment response. Reduction or stabilization of tumor size on follow-up imaging was accepted as local control, whereas tumor enlargement indicated local failure. INSTRUMENTATION: This battery-powered miniature x-ray generator device produces low-energy x-ray photons that are attenuated rapidly within tissue. A dose decline rate proportional to 1/r3 yields extremely sharp dose fall-off curves with minimal exposure to surrounding tissue. Dose rates of 200 cGy per minute are possible, allowing for the administration of 12.5 Gy to a lesion 3 cm in diameter in less than 1 hour. RESULTS: Local control (stabilization or reduction in lesion size) was obtained in 10 of the 13 patients with tumors with follow-up of 1.5 to 36 months (mean, 12 mo). Of three patients with radiographic progression, recurrence was symptomatic in only one. All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation. CONCLUSIONS: Preliminary experience with this novel radiosurgical device has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter study.
A miniaturized culture test (strep test) was compared with conventional sheep blood agar (SBA) for the detection of Group A streptococci (GAS) from throat swabs. A total of 355 throat cultures were obtained in duplicate from symptomatic children and assessed by the two methods after overnight incubation. GAS were detected in 109 specimens by the strep test, in 100 specimens by SBA and in 118 specimens by both methods. There was no significant difference between the recovery rate of GAS by the strep test (92.4%) and SBA (84.7%) (0.1 greater than P greater than 0.05). The strep test was 85.2% specific for detection of GAS. The rates of false positive and false negative reactions with the strep test were 24.3 and 4.3%, respectively. Beta-hemolytic streptococci other than Group A, Staphylococcus aureus and alpha-hemolytic streptococci produced false positive reactions. The viability of GAS on the strep test was also tested. GAS were recovered from 27 of 28 (96.4%) strep tests at 24 hours and 25 of 27 (92.6%) tests at 72 hours after inoculation. These results indicate that strep test is as sensitive as the conventional SBA method in recovering GAS. The strep test is simple to use, is easy to interpret and has a long shelf life. Because of the high rate of false positive results (24.3%), this test may not be the best alternative method to SBA for use in office practice.
Intraosseous infusions are commonly used in pediatric emergencies. Although this technique is often lifesaving, significant complications can develop from incorrect needle placement. Current methods of evaluating needle position rely on the operator's experience with the procedure. We describe the use of a miniature C-arm imaging device to accurately confirm proper needle placement.
PURPOSE OF REVIEW: The function is described of the Implantable Miniature Telescope, which is completing clinical development for bilateral end-stage macular degeneration, and 6-month results of the Phase II/III IMT002 prospective, multicenter study are presented. Multispecialty patient management and implications of the study's findings are discussed. RECENT FINDINGS: No medical treatments are currently available for bilateral end-stage age-related macular degeneration (atrophic or disciform scar age-related macular degeneration). The visual prosthetic device discussed in this update is implanted in the posterior chamber to reduce the impact of the scotomata on the patient's central vision. The goal of treatment is to improve the patient's ability to perform everyday activities and participate in roles and hobbies that impact their quality of life. Patients implanted with the device experienced clinically significant gains in visual acuity and quality of life at 6 months. In total, 89% gained two or more lines of best-corrected near or distance visual acuity. The device was generally safe and well tolerated. The surgical technique is important to minimize surgically related reduction in endothelial cell density. SUMMARY: This age-related macular degeneration visual prosthesis has been shown to improve visual acuity and quality of life for the bilateral end-stage age-related macular degeneration patient population that at present has no other acceptable options. Endothelial cell density from baseline to 6 and 12 months after device implantation was reduced due to trauma from the surgical procedure, but was compatible with a healthy cornea. Meticulous surgical technique and a comprehensive, multispecialty approach to preoperative and postoperative patient management are essential for successful outcomes.
PURPOSE: To test the safety and efficacy of the Ex-PRESS miniature glaucoma device when it is implanted under a scleral flap instead of under the conjunctiva as it was originally suggested. PATIENTS AND METHODS: Between November 2000 and February 2003, the Ex-PRESS implant was inserted in 24 eyes of 23 patients with severe open angle glaucoma. Sixteen eyes of the 24 (66%) had had previous failed filtering surgery. The remaining 8 eyes (33%) were high risk for failures cases. A 5 x 5 mm limbal-based, 50% depth, scleral flap was raised into clear cornea. The Ex-PRESS implant was inserted into the anterior chamber under the scleral flap at the limbus. The scleral flap was securely sutured back, as is done in trabeculectomy operations. RESULTS: The intraocular pressure was significantly reduced from 27.2 +/- 7.1 mm Hg pre-operatively to 14.5 +/- 5.0 mm Hg at 12 months (n = 21) and 14.2 +/- 4.2 mm Hg at 24 months (n = 8). Postoperatively, only two patients needed anti-glaucoma medications to keep the IOP below 21 mm Hg. CONCLUSIONS: The Ex-PRESS device was found to be safe and effective with few complications when it is implanted under a scleral flap even in the high-risk patients studied.
To elucidate the potential role of porcine RANTES (Regulated upon Activation Normal T cells Expressed and Secreted) in xenograft rejection, we investigated its chemotactic activity for human mononuclear cells, as well as the effect of human cytokines on its expression in porcine endothelial cells. Porcine RANTES cDNA was successfully cloned from aortic endothelial cells of miniature pigs, and its protein expression was induced by transfection. Its deduced amino acid sequence was 83.5% identical to that of human RANTES. Porcine RANTES triggered transmigration of human mononuclear cells across the species barrier, and this chemotactic effect was suppressed by anti-RANTES neutralizing antibodies. The chemotactic effect of porcine RANTES was most prominent on human monocytes. Human tumor necrosis factor-alpha induced significant expression of porcine RANTES messenger RNA in endothelial cells; however both human interferon-gamma and interleukin-1beta failed. These results suggest that porcine RANTES can play an important role in xenotransplant rejection, through participating in the interaction between porcine endothelial cells and human monocytes.
4-Aminoquinoline (4-AQ) in concentrations around 200 micrometers induces, within minutes of its application to isolated mouse or rat neuromuscular junctions, the appearance of a population of miniature endplate potentials (m.e.p.ps) with a larger than normal amplitude, so-called giant m.e.p.ps (g.m.e.p.ps). With amplitudes 2-12 times the modal value of m.e.p.p. amplitude, the population of g.m.e.p.ps varied between 15 and 45% of the total population of m.e.p.ps. There was no increase in the frequency of m.e.p.ps but a positive correlation between the frequency of g.m.e.p.ps and the total frequency of m.e.p.ps. In many instances the rise time and decay time of g.m.e.p.ps were prolonged compared to normal. Elevated extracellular calcium concentrations increased the frequency of m.e.p.ps but had no effect on g.m.e.p.p. frequency. High extracellular potassium concentrations markedly increased m.e.p.p. frequency but failed to influence g.m.e.p.p. frequency. Similar observations were made with ethanol 0.1 M, ouabain 200 micrometers or black widow spider venom. Botulinum toxin type A markedly reduced total m.e.p.p. frequency but 4-AQ still induced g.m.e.p.ps. Nerve stimulation failed to release quanta corresponding to the g.m.e.p.ps. G.m.e.p.ps seemed to originate from quantal acetylcholine release from the nerve terminal since they were abolished by surgical denervation and by the addition of d-tubocurarine to the medium. Blockade of voltage-sensitive calcium or sodium channels by, respectively, manganese ions or tetrodotoxin failed to affect the appearance and the frequency of g.m.e.p.ps. The electrophysiological findings and a statistical analysis of the characteristics of the m.e.p.ps indicate that they belong to two populations. One population is accelerated by the depolarization-release coupling mechanism responsible for evoked transmitter release and is characterized by an amplitude distribution and a process in time that indicate that they correspond to releases occurring at 'active zones' in the nerve terminal. The second population of m.e.p.ps is uninfluenced by nerve terminal depolarization and transmembrane calcium fluxes. This population apparently originates from sites dispersed in the nerve terminal membrane and outside the 'active zones'. 4-AQ increases the frequency of this second m.e.p.p. population without affecting the first population.