PubMed Health⌕ Search

Biomedical subjects

R Josephson

Publications and source records attributed to R Josephson.

14 recordsLinked to original sources
PubMed1998

POU transcription factors control expression of CNS stem cell-specific genes.

Multipotential stem cells throughout the developing central nervous system have common properties. Among these is expression of the intermediate filament protein nestin and the brain fatty acid binding protein (B-FABP). To determine if common mechanisms control transcription in CNS stem cells, the regulatory elements of these two genes were mapped in transgenic mice. A 257 basepair enhancer of the rat nestin gene is sufficient for expression throughout the embryonic neuroepithelium. This enhancer contains two sites bound by the class III POU proteins Brn-1, Brn-2, Brn-4, and Tst-1. Only one of the two POU sites is required for CNS expression. An adjacent hormone response element is necessary for expression in the dorsal midbrain and forebrain. The regulatory sites of the B-FABP gene are strikingly similar to those of the nestin gene. A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2. This site is essential for expression in most of the CNS. In addition, a hormone response element is necessary for forebrain expression. Both the nestin and B-FABP genes therefore depend on POU binding sites for general CNS expression, with hormone response elements additionally required for activity in the anterior CNS. These data indicate that regulation by POU proteins and hormone receptors is a general mechanism for CNS stem cell-specific transcription.

Animals↗
PubMed1997

Power output from a flight muscle of the bumblebee Bombus terrestris. I. Some features of the dorso-ventral flight muscle

1. Isometric contractions from the asynchronous dorso-ventral flight muscle of the bumblebee Bombus terrestris were slow and rather weak. The twitch duration (onset to 50 % relaxation) was approximately 300 ms at 30 °C and 170 ms at 40 °C. The maximum tetanic tension was approximately 40 kN m-2; the ratio of twitch force to tetanic force was approximately 0.2. 2. The unstimulated muscle was quite resistant to stretch, with a low-frequency stiffness of 730 kN m-2 at muscle lengths close to that of the muscle in vivo. The length­tension curve for active tetanic tension (that is the increase in tension above the passive level during stimulation) was very narrow, with a half-width equal to only 17 % of the optimal length. 3. The muscle strain during tethered flight was approximately 2 % peak-to-peak, occasionally reaching 3 %. Strain amplitude increased with wing stroke frequency. The thoracic vibration frequency of escape buzzing, during which the wings are not extended but are folded over the abdomen, was approximately twice that of tethered flight but the muscle strain was similar to that of flight.

Journal Article↗
PubMed1997

Power output from a flight muscle of the bumblebee Bombus terrestris. II. Characterization of the parameters affecting power output

1. Length-tension relationships and work output were investigated in the intact, dorso-ventral flight muscle of the bumblebee Bombus terrestris. The muscle is an asynchronous muscle. Like other asynchronous flight muscles, it has high resting stiffness and produces relatively low active force in response to tetanic stimulation. 2. The muscle shows shortening deactivation and stretch activation, properties that result in delayed force changes in response to step changes in length, a phase lag between force and length during imposed sinusoidal strain and, under appropriate conditions, positive work output during oscillatory length change. 3. Work loops were used to quantify work output by the muscle during imposed sinusoidal oscillation. The curves relating net work per cycle with muscle length, oscillatory strain and oscillatory frequency were all roughly bell-shaped. The work-length curve was narrow. The optimum strain for net work per cycle was approximately 3 %, which is probably somewhat greater than the strain experienced by the muscle in an intact, flying bumblebee. The optimum frequency for net work output per cycle was 63 Hz (30 °C). The optimum frequency for power output was 73 Hz, which agrees well with the normal wing stroke frequency if allowance is made for the elevated temperature (approximately 40 °C) in the thorax of a flying bumblebee. The optimal strain for work output was not strongly dependent on oscillation frequency. 4. Resilience (that is the work output during shortening/work input during lengthening) for unstimulated muscle and dynamic stiffness (=stress/strain) for both stimulated and unstimulated muscles were determined using the strain (3 %) and oscillation frequency (64 Hz) which maximized work output in stimulated muscles. Unstimulated muscle is a good energy storage device. Its resilience increased with increasing muscle length (and increasing resting force) to reach values of over 90 %. The dynamic stiffness of both stimulated and unstimulated muscles increased with muscle length, but the increase was relatively greater in unstimulated muscle, and at long muscle lengths the stiffness of unstimulated muscle exceeded that of stimulated muscle. Effectively, dynamic stiffness is reduced by stimulation! This is taken as indicating that part of the stiffness in an unstimulated muscle reflects structures, possibly attached cross bridges, whose properties change upon stimulation.

Journal Article↗
PubMed1997

Power output from a flight muscle of the bumblebee Bombus terrestris. III. Power during simulated flight

1. The work loop approach was used to measure mechanical power output from an asynchronous flight muscle, the dorso-ventral muscle of the bumblebee Bombus terrestris. Measurements were made at the optimum muscle length for work output at 30 °C and at a muscle temperature (40 °C) and oscillatory frequency (141­173 Hz, depending on the size of the animal) characteristic of free flight. Oscillatory strain amplitude was adjusted to maximize power output. 2. There was much preparation-to-preparation variability in power output. Power output in the muscles with the highest values was slightly greater than 100 W kg-1. It is argued that there are many experimental factors which might reduce measured power output below that in the living bumblebee, and no obvious factors which might lead to overestimates of muscle power. The conclusion is that flight muscle in the intact bumblebee can produce at least 100 W kg-1.

Journal Article↗
PubMed1995

Influence of muscle length on work from trabecular muscle of frog atrium and ventricle

The work capacity of segments of atrial and ventricular muscle from the frog Rana pipiens was measured as a function of muscle length using the work loop technique. Both the work done during shortening and the work required to re-lengthen the muscle after shortening increased with muscle length. Net work increased with length up to a maximum, beyond which work declined. The optimum sarcomere length for work output was 2.5­2.6 µm for both atrial and ventricular muscle. Isometric force increased with muscle length to lengths well beyond the optimum for work output. Thus, the decline in work at long lengths is not simply a consequence of a reduction in the capacity of heart muscle to generate force. It is proposed that it is the non-linear increase in work required to re-lengthen muscle with increasing muscle length which limits net work output and leads to a maximum in the relationship between net work and muscle length. Extension of the results from muscle strips to intact hearts suggests that the work required to fill the ventricle exceeds that available from atrial muscle at all but rather short ventricular muscle lengths.

Journal Article↗
PubMed1994

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - ACTIVATION PATTERNS IN VIVO

1. The flagella of crustaceans are small appendages, borne on the maxillipeds, which beat repetitively when active. Flagellar movement is brought about by contraction of a single muscle, the flagellum abductor (FA). 2. The stroke frequency of the flagella of the green crab, Carcinus maenas, was about 11 Hz at 15 °C and was relatively independent of animal size [frequency is proportional to (animal mass)-0.07], even though scaling considerations suggest that, for constant muscle stress, frequency should be proportional to mass-0.33. The coefficient of variation for intervals between successive strokes of a flagellum was about 4 %. 3. The FA is innervated by two excitatory motoneurones. Each of the neurones fired 0­5 times during a stroke. The interspike interval when a neurone fired more than once during a stroke was 3­4 ms.

Journal Article↗
PubMed1994

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - CONTRACTION KINETICS

1. The flagella (small appendages on the maxillipeds) of the crab Carcinus maenas beat regularly when active at about 10 Hz (15 °C). The beat of a flagellum is due to contraction of a single small muscle, the flagellum abductor (FA). The optimal stimulus frequency for tetanic contraction of the FA was about 200 Hz. When the muscle was stimulated at 10 Hz with paired stimuli per cycle, the interstimulus interval that maximized peak force was 2­4 ms, which corresponded well to the interspike intervals within bursts recorded from motor axons during normal beating. 2. Contraction of the isolated FA showed pronounced neuromuscular facilitation and many stimuli were needed to activate the muscle fully. The dependence on facilitation in isolated muscles appeared to be greater than that in vivo. It is suggested that neuromodulators in the blood of the crab enhance neuromuscular transmission and reduce the dependency on facilitation in intact animals. 3. The FA had a narrow length­tension curve. Tetanic tension became vanishingly small at muscle lengths less than about 90 % of the maximum in vivo length. The maximum length change of the muscle during in vivo contraction was about 5 %. 4. The maximum isometric force of the FA was low (about 6 N cm-2) but its shortening velocity was high. Vm, the maximum shortening velocity determined from isotonic shortening, was 4.0 muscle lengths s-1; V0, the maximum shortening velocity from slack test measurements, was about 8 lengths s-1. 5. The structure and physiology of the FA are compared with those of locust flight muscle, chosen because it too is a muscle capable of long-duration, high-frequency performance.

Journal Article↗
PubMed1994

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - MECHANICAL POWER OUTPUT

The mechanical power output during oscillatory contraction was determined for the flagellum abductor muscle of the crab Carcinus maenas using the work loop technique. Measurements were made at 10 Hz, which is the normal operating frequency of the muscle. The temperature was 15 °C. Increasing the number of stimuli per cycle (given at an interstimulus interval of 3.3 ms) decreased the number of cycles required to reach a work plateau and increased the work per cycle at the plateau to a maximum at 4­5 stimuli per cycle. The maximum mechanical power output was 9.7 W kg-1 muscle (about 26 W kg-1 myofibril). The optimum strain for work output (5.7 %) was close to the estimated muscle strain in vivo (5.2 %).

Journal Article↗
PubMed1993

Development of a program for identification of patients with familial hypercholesterolemia in British Columbia: a model for prevention of coronary disease.

We have developed a targeted approach to identification of high-risk patients in British Columbia, Canada, as an initial strategy for the prevention of coronary disease. Patients with the diagnosis of familial hypercholesterolemia have been identified through the Lipid Clinic. First degree relatives of these persons and subsequently identified individuals will be screened for the presence of hypercholesterolemia. Using this approach, the likelihood of identifying persons at high risk is high, close to 50%. The program will also allow collection of data on factors affecting the expression of hyperlipidemia and atherosclerosis and their response to therapy. In an effort to establish the infrastructure that would be necessary for identification and management of such patients throughout the province, a Lipid Clinic Outreach Program has been developed. The objective is to provide each community in the province with expertise to manage hyperlipidemia without traveling to a major urban area. With this infrastructure in place, this will serve patients who have premature atherosclerosis due to other causes and will also form the framework for dissemination of heart health policies and programs by different levels of government, voluntary and professional organizations, as well as the private sector. From a targeted family centered pilot program, a broad approach to the prevention of coronary artery disease in this community will be possible.

Ambulatory Care↗
PubMed1989

Morphological and contractile characteristics of rat cardiac myocytes from maturation to senescence.

Morphological and contractile characteristics of individual myocytes isolated from rats of 2, 6-9, and 24-25 mo of age were measured. The average myocyte length measured under high power light microscopy in unattached cells increased from 133 microns at 2 mo to 146 microns at 6-9 mo to 162 microns at 24-25 mo of age. The average slack sarcomere length was 1.85, 1.83, and 1.82 microns at 2, 6-9, and 24-25 mo, respectively. The average cell volume measured via Coulter counter techniques approximately doubled between 2 and 24 mo. During the electrically stimulated twitch in individual unloaded myocytes contracting from slack length the absolute amplitude of cell shortening increased with age, but when expressed relative to cell length or as sarcomere shortening the age effect was obliterated. Neither the maximal velocity of myocyte shortening (cell length/s) nor the calculated maximal sarcomere shortening velocity varied with age. The time course of the twitch increased with aging, due largely to an increase in the time to peak shortening. Thus aging is associated with an increase in cell size due to the addition of sarcomeres. Except for a prolonged time course, the twitch contraction characteristics normalized for cell length and sarcomere number in unloaded ventricular myocytes contracting over a range of sarcomere lengths below the slack length do not change appreciably with age.

Aging↗
PubMed1985

Clinical and histological evidence for the presence of the vomeronasal (Jacobson's) organ in adult humans.

One hundred adult humans were examined specifically for the presence of the opening of the vomeronasal organ (VNO) on the antero-inferior part of the nasal septum. This was found in 39% of patients. Twenty-seven human septums were removed at post mortem, examined macroscopically, sectioned coronally and examined microscopically. In 70% of these specimens, vomeronasal structures were identified. Histological examination failed to reveal any evidence that these organs may be functional. The human embryology and comparative anatomy of the VNO are reviewed. The physiological function in different vertebrates is also considered, and the significance of the findings in this study is assessed in the light of this evidence.

Adolescent↗
PubMedDate not supplied

Intra-aortic balloon pump complications: A five-year retrospective study of 283 patients.

OBJECTIVE: To determine the type, incidence, and risk factors for complication with the intra-aortic balloon pump. DESIGN: Descriptive, chart review. SETTING: Midwestern community teaching hospital. PATIENTS: Two hundred eighty-three patients with 287 intra-aortic balloon pump insertions from January 1, 1990, to December 31, 1994. OUTCOME MEASURES: Complications of therapy. RESULTS: Seventeen percent of balloon insertions resulted in minor complications, and 14 patients had major complications. Polychotomous logistic regression was used to determine which study risk factors were predictive of the development of minor or major complications in patients. Patients with longer balloon duration had an increased risk of a major complication; whereas smokers and patients with lower body mass index had an increased probability of the development of a minor complication.

Adult↗