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Biomedical subjects

P R Murphy

Publications and source records attributed to P R Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1985

Impulse rates and sensitivity to stretch of soleus muscle spindle afferent fibers during locomotion in premammillary cats.

Impulse from soleus muscle afferents were recorded in premammillary cats that were walking on a treadmill. In normal walking the effects of gamma-motoneurons on impulse rates of muscle spindle afferents are confounded by the effects of the large length changes that occur. To isolate the effects of gamma-motoneurons the leg was fixed in place for recording and denervated except for soleus muscle. Because gamma-motoneurons produce marked effects on the stretch sensitivity of muscle afferents, soleus muscle was oscillated about a present length so the stretch sensitivity of its afferents could be determined. The impulse rate of secondary muscle spindle afferents in soleus muscle was generally increased at all phases of the step cycle. The mean rate approximately doubled during walking (82 imp/s), compared with nonwalking (rest) periods (44 imp/s). The sensitivity to sinusoidal length changes was generally reduced throughout the step cycle (mean reduction = 33%). Primary muscle spindle afferents also showed an increased mean rate during walking (47 imp/s) compared with rest (24 imp/s). The impulse rate peaked after the muscle reached its maximum force and often showed a second peak before the maximum electromyogram (EMG) activity. The sensitivity to sinusoidal stretches varied cyclically during locomotion. During the extension phase it sometimes exceeded the resting value, but was greatly reduced during the flexion phase (mean reduction = 49% over whole cycle). Control experiments were carried out in which static and dynamic gamma-motoneurons were stimulated and activity from muscle spindle afferents was recorded in anesthetized cats. With the amplitude and frequency of stretch applied, stimulation of dynamic gamma-motoneurons usually increased and stimulation of static gamma-motoneurons usually decreased the sensitivity of primary muscle spindle afferents to sinusoidal stretch. The patterns observed in muscle spindle afferents suggest a strong, maintained activation of static gamma-motoneurons throughout the step cycle and a phasic activation of dynamic gamma-motoneurons, which is consistent with previous direct recordings from gamma-motoneurons. With this pattern of activating gamma-motoneurons, the secondary muscle spindle afferents will provide a good feedback signal of the large length changes that normally occur in the muscle during locomotion. The changes in sensitivity of primary muscle spindle afferents will complement central changes so the gain of the stretch reflex from extensors is high during extension (when required to help support the weight of the body) and low during flexion (when a high gain would be counterproductive).

Anesthesia, General↗
PubMed1985

Human growth hormone induces and maintains c-myc gene expression in Nb2 lymphoma cells.

The effect of human GH (hGH) on c-myc gene expression and cell proliferation in the Nb2 lymphoma cell line was examined. The addition of hormone to stationary cultures of Nb2 cells resulted in an increased accumulation of c-myc transcripts that was detectable within 15 min, reached a maximum induction of 25-fold in 3 h, and then gradually declined. Although maximal accumulation of c-myc transcripts occurred within 3 h after hGH addition, removal of the hormone even after 4 h of treatment resulted in a failure of the cells to proliferate. This loss of proliferative capacity following hormone removal was accompanied by a 20-fold reduction in the level of c-myc transcripts. These results indicate that hGH induced proliferation of Nb2 cells is associated with the induction and maintenance of c-myc gene expression.

Cell Division↗
PubMed1984

Phasic and tonic modulation of impulse rates in gamma-motoneurons during locomotion in premammillary cats.

To determine the role of gamma-motoneurons in the control of locomotion, we isolated single units from nerves to triceps surae muscles in the premammillary cat. The limb used for recording was largely denervated, except for the muscles of interest, and fixed in place, while the other three limbs walked on a treadmill. One type of gamma-motoneuron (13 units) had a high impulse rate at rest, which changed little on average during walking, but was deeply modulated with each step (phasically modulated gamma-motoneuron or gamma p). Another type (19 units) had a low impulse rate at rest, which increased greatly on average during walking, but was not highly modulated with each step (tonically modulated gamma-motoneuron or gamma t). Peak gamma p rates generally occurred after peak EMG, often near the peak of tension. In contrast, peak gamma t activity generally preceded peak electromyograms (EMG). No significant difference was observed in conduction velocities for the two types of units. At rest all gamma t units were excited by natural stimulation of the fur over a large part of the body surface, whereas 3 of 11 gamma p units were inhibited. During locomotion the same natural stimuli had no observable effect on either type of unit. By recording in continuity from fine branches of the lateral and medial gastrocnemius nerves and stimulating ventral root filaments in continuity, we identified dynamic and static gamma-motoneurons in terms of their effects on muscle spindle afferents. After cutting the nerve branch distally and other ventral root filaments supplying the muscle, the resting discharge of dynamic and static gamma-motoneurons was recorded and found to correspond to that of the gamma p and gamma t units, respectively. Other evidence is presented for a correspondence between phasically and tonically modulated units and dynamic and static gamma-motoneurons, contrary to some suggestions in the literature.

Action Potentials↗
PubMed1984

Triphenylethylene antiestrogen-binding sites in cockerel liver nuclei: evidence for an endogenous ligand.

Salt extracts of purified nuclei from cockerel liver contain a limited number of sites that bind triphenylethylene nonsteroidal antiestrogens with high affinity and specificity. The assay of the [3H]tamoxifen (3H-labeled 1-[4-(2-dimethylaminoethyoxy)phenyl] 1,2-diphenylbut-1-(Z)ene)-binding sites is optimally achieved by preincubation of the salt extracts with charcoal-dextran suspension; a 4- to 8-fold increase in activity over that obtained with nontreated extracts is found. This suggests that the binding sites are occupied in vivo by an unknown endogenous ligand. The equilibrium dissociation constant for [3H]tamoxifen binding is 4.76 +/- 1.8 nM, and the binding site concentration is 1.7 +/- 0.7 fmol/microgram DNA. The concentration of high affinity estrogen-binding sites in the same extracts is almost 30-fold less (0.06 +/- 0.01 fmol/micrograms DNA). The relative binding affinities of various antiestrogens for the nuclear antiestrogen-binding sites (with tamoxifen arbitrarily set at 100%) are as follows: nafoxidine (1-[2-(p-[3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl]phenoxy)ethyl] pyrrolidine hydrochloride); 126%) greater than tamoxifen (100%) greater than N-des-methyltamoxifen (16%) greater than CI-628 (alpha-[p-[2-(1-pyrrolidine)ethyoxy]phenyl] 4-methoxy-alpha'-nitrostilbene; 14%) greater than 4-hydroxytamoxifen (7%). Estrogens (17 beta-estradiol, estriol, estrone, and diethylstilbestrol) and several other steroids (cholesterol, dihydrotestosterone, pregnenolone, progesterone, and hydrocortisone) show little or no affinity for binding to the nuclear sites (relative binding affinity, less than 0.5%). However, ether extracts of cockerel serum or liver nuclei contain a substance(s) that competitively inhibits [3H]tamoxifen binding to the nuclear antiestrogen-binding sites. The ether-soluble material does not compete for [3H]estradiol binding to the salt-soluble nuclear estrogen receptor. These studies suggest that cockerel serum and liver nuclei contain a natural compound which competes with the triphenylethylenes at the antiestrogen-binding site and may occupy the nuclear binding sites in vivo.

Animals↗
PubMed1983

beta-adrenergic agonist induced androgen production during primary culture of mouse Leydig cells.

Mouse testicular interstitial cells and Leydig cells prepared by density-gradient centrifugation developed the ability to increase androgen production in response to isoproterenol between 24 and 48 hr of primary culture. Although exposure of the cultures to isoproterenol or cycloheximide inhibited the acquisition of responsiveness to beta-adrenergic stimulation, in vivo treatment with propranolol did not alter the time at which cultures became responsive to isoproterenol. It is concluded that the acquisition of beta-agonist responsiveness during culture is not a recovery from beta-adrenergic desensitization.

Adrenergic beta-Agonists↗
PubMed1983

Optimization of the DTPA mixed-anhydride reaction with antibodies at low concentration.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with antibody to human serum albumin (Ab) at low concentration (300 micrograms/ml, 2.0 microM) via the DTPA carboxycarbonyl mixed-anhydride method. To study parameters determining the balance between the degree of conjugation and the antibody-binding activity of Ab, a known concentration of the anhydride prepared at isobutylchloroformate (IBC)-to-DTPA ratios of 1, 2.1, or 4.2 was reacted with Ab. The percentage yields of the anhydride were determined by spectrophotometric and gravimetric titration. By the former method the percentage yields, based on DTPA concentration, were 18, 24, and 220, respectively, when the IBC-to-DTPA ratios were 1, 2.1, and 4.2. The corresponding percentage yields were 17, 39, and 262 when determined by the latter method. When the anhydride was prepared at an IBC-to-DTPA ratio of 2.1, an optimum conjugation giving three indium atoms per Ab was obtained, with 64% retention of antibody-binding activity. For an IBC-to-DTPA ratio of 1, the antibody retained almost 100% binding activity but the number of indium atoms incorporated (0.2) was too small. For an IBC-to-DTPA ratio of 4.2, up to 22 indium atoms were incorporated but antibody-binding activity was completely destroyed.

Anhydrides↗
PubMed1983

Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with a practical concentration (300 micrograms/ml) of antibody to human albumin (Ab) and 1083 17-1A monoclonal colorectal antibody (MAb-17-1A) via an acylation reaction using cyclic DTPA anhydride (cDTPAA). The conjugation reaction was favored as pH increased. Bicarbonate buffer at pH 8.2 was chosen for studies of the effect of the cDTPAA-to-antibody ratio on DTPA conjugation with antibody because of its good buffer capacity at that pH. The reaction of cDTPAA with Ab at molar ratios of 2000, 1000, 500, and 100 in the bicarbonate buffer gave rise to 11, 9, 8, and 2 indium atoms incorporated per Ab with 47%, 55%, 59%, and 77% retention of the binding activity. For the conjugation reaction of MAb-17-1A, 29, 28, 31, 11, 4, and 1 indium atoms were incorporated, with the retention of less than 5%, less than 5%, less than 5%, 12%, 60%, and 93% of binding activity when the molar ratio was 5000, 2000, 1000, 500, 100, and 50.

Animals↗
PubMed1982

Reevaluation of the effect of follicle-stimulating hormone on the steroidogenic capacity of the testis: the effects of neuraminidase-treated FSH preparations.

The ability of FSH treatment to increase the amount of androgen produced by the testis in response to maximum LH stimulation may be an effect of the LH contamination of the FSH preparations. To examine this question, 3 FSH preparations of different potencies and degrees of LH contamination or their neuraminidase-treated derivatives were administered to hypophysectomized immature rats for 5 days. The capacity of the testes to produce androgens in vitro was assessed at the end of the treatment period. Neuraminidase treatment reduces the in vivo activity of ovine and bovine FSH but does not alter the activity of ovine or bovine LH. Neuraminidase treatment of one FSH preparation (NH-bFSH-B1) did not reduce the ability of this FSH preparation to increase the response of the testis to LH stimulation in vitro. This suggests that the considerable LH contamination of the NIH-bFSH-B1 may be responsible for its effect. However, neuraminidase treatment of 2 more highly purified FSH preparations (bFSH-199C and NIH-oFSH-S13) abolished or greatly reduced the ability of these preparations to increase testicular weight and the response to LH in vitro. It is concluded that the ability of highly-purified FSH preparations to increase the amount of androgen produced by the testis is due to FSH activity and not the contaminating LH.

Androgens↗
PubMed1982

Short-term primary culture of mouse interstitial cells: effects of culture conditions of androgen production.

This study examined the effects of culture conditions and hormone treatment on androgen production by mouse interstitial cells in short-term primary culture. Testicular interstitial cells (18-25% 3 beta-hydroxysteriod dehydrogenase-positive) were maintained in serum-free hormone supplemented medium. Basal (nonstimulated) androgen production was found to be plating-density dependent. Androgen production per cell increased dramatically in a time- and cell concentration-dependent manner. This effect was reproduced in low density cultures by addition of charcoal-stripped conditioned medium from high density cultures. The cell anchorage factors, fibronectin and poly-l-lysine, similarly enhanced basal androgen production but did not augment responsiveness to luteinizing hormone (LH). Coating of the culture surface with serum inhibited androgen production. Cultured cells remained responsive to LH for 4 to 5 days and both insulin (5 micrograms/ml) and epidermal growth factor (EGF) (3 ng/ml) augmented LH-stimulated androgen production. There was a transient increase in LH sensitivity and maximum LH-stimulated androgen production for 5 to 72 h in culture followed by a decline in androgen production to low levels after 4 to 5 days in culture. This loss of activity was partially prevented by addition of antioxidants to the medium or by reduction of the ambient O2 concentration to 1%.

Androgens↗
PubMed1982

Closely coupled excitation of gamma-motoneurones by group III Muscle afferents with low mechanical threshold in the cat.

1. The reflex responses of gamma-motoneurones to discharges of muscle receptors innervated by Group III axons have been examined in hind-limb muscles of decerebrated and spinal cats.2. Electrical stimulation of the gastrocnemius medialis nerve at a strength sufficient to excite Group III axons caused excitation of gastrocnemius lateralis or soleus gamma-motoneurones. The excitation was more prominent in the spinal animal.3. Excitation of either silent or tonically firing gamma-motoneurones was a secure, driven type of response consisting of one or two spikes occurring at fairly fixed latency in response to a single stimulus. Eighteen out of thirty-nine gamma-motoneurones studied showed such excitation.4. Subtracting peripheral conduction times of the gamma-motoneurone impulse and the earliest component of the Group III volley from the latency of reflex excitation gave a range of central delays of 1.8-4.8 msec (mean 3.0 msec).5. Inhibitory Group III effects were also seen but were less pronounced than the excitation.6. The origin of the receptors connected to the Group III axons whose discharge causes driven excitation of gamma-motoneurones was investigated.7. Isometric twitch contractions of a muscle caused pronounced facilitation or excitation of homonymous and heteronymous gamma-motoneurones. Excitation occurred close to the peak or during relaxation of the twitch with a range in latency of 30-110 msec. The muscles studied were triceps surae, flexor digitorum and hallucis longus.8. Pressure or light taps applied to the gastrocnemius medialis muscle caused an increase in discharge frequency in twenty out of twenty-eight gamma-motoneurones of the same muscle (four were inhibited). The response to a steady stimulus adapted but could outlast it by many seconds. Pressure was more effective when applied to the proximal or distal parts of the muscle.9. Fifteen out of thirty-eight gastrocnemius medialis receptors having Group III axons (conduction velocities 5-27 m/sec) were found to discharge one, or occasionally two, spikes to twitch contractions of the parent muscle at latencies of 30-80 msec.10. Eight out of ten receptors with Group III axons that responded to contraction had low thresholds to pressure and taps, whereas the majority of the twenty-three Group III units which were insensitive to contraction had high thresholds to such stimuli. Receptive fields of all Group III units were confined to either the proximal third or distal third of gastrocnemius medialis or, in a few instances, the Achilles tendon.11. We conclude that discharges in Group III axons from receptors which respond to non-noxious, low threshold mechanical stimuli cause a tightly coupled excitation of gamma-motoneurones. The likely contribution of this reflex to the control of movement is discussed.

Action Potentials↗
PubMed1982

The patterns of discharge of static and dynamic gamma motoneurones in the decerebrate rabbit.

1. The effect of natural stimulation of the limbs (usually pinching the forepaws) on the discharges of muscle spindle primary and secondary afferents and gamma motoneurones of the gastrocnemius medialis muscle were examined in the precollicular decerebrate rabbit, paralysed with gallamine triethiodide to prevent extrafusal muscle contraction. 2. The afferents showed only excitation in response to natural stimulation. The same stimulus strongly inhibited some gamma motoneurones and, at the same time, predominantly excited others. 3. Since extrafusal muscle contraction was prevented using gallamine triethiodide, intrafusal contraction was responsible for the afferent excitation, and could only have been evoked by those gamma motoneurones excited by natural stimulation. The distribution of effects from gamma motoneurones that were strongly inhibited by natural stimulation could not be deduced from afferent recordings. 4. On the basis of these afferent and efferent recordings, and the known structure of the muscle spindle, gamma motoneurones were identified as static or dynamic. 5. The results are discussed in relation to the patterns of discharge of static and dynamic gamma motoneurones.

Action Potentials↗
PubMed1981

A comparison of the recurrent inhibition of alpha- and gamma-motoneurones in the cat.

1. The degree of recurrent inhibition of tonically firing alpha- and gamma-motoneurones to triceps surae muscles was assessed in decerebrated cats by measuring the change in probability of firing caused by an antidromic volley in other motoneurone axons. 2. In nine cats 91% (thirty-one out of thirty-three) of alpha- and 54% (twenty-five out of forty-six) of gamma-motoneurones could be inhibited by antidromic volleys in alpha-motoneurone axons. 3. The degree of recurrent inhibition, expressed as the average reduction in probability of firing during the response, was typically in the range of 59-95% for alpha-motoneurones compared to 20-85% for gamma-motoneurones. 4. The duration of recurrent inhibition was 20-50 msec for alpha-motoneurones and 5-40 msec for gamma-motoneurones. The duration was dependent upon the frequency of firing of a neurone, being shorter at high frequencies than at low frequencies. When alpha- and gamma-motoneurones had similar frequencies of discharge the durations of their recurrent inhibition were comparable. 5. Raising the strength of electrical stimulation to elicit an antidromic volley in gamma- as well as alpha-motoneurone axons never produced or increased recurrent inhibition in either type of motoneurone. 6. The quantitative differences in recurrent inhibition of alpha- and gamma-motoneurones are discussed in relation to the control of firing frequency.

Action Potentials↗
PubMed1981

The recruitment order of gamma-motoneurones in the decerebrate rabbit.

1. The order of firing (i.e. recruitment order) of gastrocnemius medialis gamma-motoneurones to natural stimulation of the limbs has been studied in the precollicular decerebrate rabbit. 2. Recruitment order was not invariable. However, when a fixed order occurred there was a significant tendency for neurones to be recruited in order of increasing axonal conduction velocity. The functional significance of this finding is discussed. 3. In the preparation used, many gamma-motoneurones were spontaneously active. 4. Two types of gamma-motoneurone were distinguished on the basis of their resting discharge characteristics and responses to natural stimulation. 5. A significant correlation between resting discharge frequency and axonal conduction velocity was found for gamma-motoneurones that were predominantly excited by natural stimulation.

Action Potentials↗
PubMed1980

Autogenetic effects of muscle contraction on extensor gamma motoneurones in the cat.

The effect of isometric twitch contractions of hind limb muscles on the discharge of gamma motoneurones has been studied in decerebrated cats with thoracic spinal cord section. Contractions of flexor digitorum longus (FDL) or gastrocnemiussoleus (GS) strongly inhibited the background discharge of their homonymous gamma motoneurones. In contrast, contraction of FDL generally caused less inhibition, or did not affect the discharge, of the synergist GS gamma motoneurones. Both the autogenetic and synergist inhibition were considerably weaker in decerebrated cats with intact spinal cords. The inhibition lasted 20 to 50 ms and occurred principally during the rising phase of contraction. It could be followed or terminated by a weaker period of facilitation during relaxation of the muscle. Shortening the muscle so that no active tension developed during contraction either abolished or substantially curtailed the inhibition. We discuss the probability that the inhibition is a spinal segmental reflex brought about by impulses generated in Ib afferents of tendon organs. The inhibition is under tonic inhibitory control in the decerebrated cat when the spinal cord is intact. Unlike the Ib inhibition of alpha motoneurones that of gamma motoneurones has a particularly strong autogenetic component.

Animals↗
PubMed1979

Inhibition of gamma motoneurone discharge by contraction of the homonymous muscle in the decerebrated cat.

1. The aim of this study has been to determine the autogenetic reflex effects of tendon organ stimulation upon gamma motoneurones in the decerebrated cat. 2. Tendon organs serving a muscle were excited by isometric twitch contractions of some motor units of that muscle. Contractions were elicited by electrical stimulation of the cut peripheral end of part of the ventral root supply, using a stimulus strength at or below maximum for alpha motoneurone axons. Afferent recordings in the same cats as were used to study reflexes of gamma motoneurones showed that tendon organs were powerfully excited during twitch contractions of their muscle. Early discharges were also elicited in both tendon organs and spindle primary afferents. 3. Background discharges of forty-seven triceps surae gamma motoneurones, ranging in axonal conduction velocity from 17 to 40 m/sec, were recorded from filaments of the muscle nerve. The initial response of twenty-two (47%) neurones to twitches of the triceps surae was inhibition of their discharge. The latency from time of stimulation of the ventral root ranged from 10 to 22 msec. The lowered probability of firing lasted an average of 25 msec and, occasionally, was seen as a short silent period. 4. The inhibition was reduced in duration by decreasing the resting muscle length so that less active tension was developed during contraction. 5. The inhibition was observed, in one instance, in the spinally transected decerebrated cat. 6. We argue the case that early discharges in tendon organ afferents give rise to the onset of inhibition and that tension dependent discharges of tendon organs contribute further inhibition of gamma motoneurones. 7. Sixteen gamma motoneurones were not affected by contraction but seventeen showed a period of facilitation. The facilitation could occur after a period of inhibition (eight neurones) or as the sole response to contraction. In either case facilitation occurred mainly during relaxation of the muscle and may, in part, be attributable to increased spindle primary ending firing at this time. 8. In discussion a comparision is made of the reflex effects of muscle afferent discharges on alpha and gamma motoneurones.

Action Potentials↗