Neurofilamentous hypertrophy of intramedullary axonal arbors in intact spinal motoneurons undergoing peripheral sprouting

An incomplete motor nerve injury or a partial loss of motoneurons leads to a partial denervation of skeletal muscle. As part of a compensatory response, the remaining intact motoneurons undergo peripheral sprouting and increase their motor unit size. Our knowledge about the responses in the more proximal parts of these sprouting motoneurons is sparse, however. We investigated the effects of an incomplete transection of the medial gastrocnemius (MG) nerve in the adult cat on the morphology of the intramedullary axon and axon collateral systems of the remaining intact MG motoneurons. At twelve weeks following the partial transection of the MG nerve, intracellular recording and labeling techniques were used to deposit horseradish peroxidase into single intact MG motoneurons for detailed morphological studies. The light microscopic appearance and caliber of the intramedullary stem motor axons of the intact MG motoneurons were indistinguishable from controls. The number and size of the intramedullary motoraxon collateral systems were also unchanged. However, frequent and marked hypertrophy of the distal portions of the motoraxon collaterals was encountered. Electron microscopic studies of the hypertrophied collaterals demonstrated abnormal accumulations of disorganized neurofilaments arranged in bundles or whorls. The morphological changes were indistinguishable from the neurofilamentous hypertrophy that has previously been reported in Wallerian degeneration, in experimental and human motor neuron disease and in some regenerating axonal processes of spinal motoneurons. We conclude that, neurofilamentous hypertrophy of the intramedullary arbors of motor axons may also be part of a reactive and non-degenerative response in intact motoneurons undergoing compensatory peripheral sprouting.     

The Postnatal Development of Some Twitch and Fatigue Properties of Single Motor Units in the Ankle Muscles of the Kitten

Contractions of single motor units in the gastrocnemius, soleus and pretibial flexor muscles were elicited by intracellular stimulation of the innervating motoneurones. Kittens being 1, 2, 6 and 10 weeks of age were used. The aim was to establish the pattern of postnatal differentiation of the adult motor unit types (Burke et al. 1973, 1974, Hammarberg and Kellerth 1975 b). In the developing type S units of the soleus muscle the mean value for contraction time showed a transient decrease during the early postnatal period, but the twitch half-relaxation time (HRT), the duration of motoneurone post-spike afterhyperpolarization (AHP) and the susceptibility to fatigue remained virtually unchanged during the age period studied. In the units of the developing fast twitch muscles the contraction time, HRT and susceptibility to fatigue were significantly different from those of the soleus units already at 1 week of age. At 6–10 weeks of age the contractile characteristics typical of the adult type FF and FR units were attained. The AHP duration gradually decreased up to 10 weeks of age, and it was then considerably shorter than both at 1 week of age and in the adult stage.     

The Amino Acid Composition of Hemoglobin. V. The Preparation of Purified Hemoglobin Fractions by Chromatography on Cellulose Exchangers and Their Identification by Starch Gel Electrophoresis Using Tris-Borate-EDTA Buffer

The chromatographic separation of hemoglobin on two cellulose exchangers,CMC and DEAE, is discussed. Problems related to the use of these technicsare described. In addition, our experience with the use of Tris-Borate-EDTAbuffer (Smithies) for hemoglobin electrophoresis in starch gel is presented.

Submitted on May 4, 1964 Accepted on July 14, 1964     

Intrauterine Fetal Surgery A Nursing Challenge

Surgical treatment of the fetus In utero offers new options for selected families with fetal anomalies. Nurses caring for these families must be prepared to meet their unique needs. The diagnosis, treatment, support, and follow-up care of the family is discussed.     

Intracellular autogenetic and synergistic effects of muscular contraction on flexor motoneurones

1. Intracellular records have been taken from cat motoneurones innervating flexor muscles of the hind limb. Contractions of the ankle flexors tibialis anterior and extensor digitorum longus were elicited by stimulation of the peripheral end of the cut L 7 ventral root and the reflex effects of these contractions were recorded in silent and repetitively firing motoneurones.

2. Contraction usually produces a hyperpolarizing response inside flexor motoneurones. This hyperpolarization is tension-sensitive in the sense that when, at constant muscle extension, the strength of the contraction is increased, the magnitude of the inhibitory response is augmented.

3. Increasing the resting length of the muscles, while using a stimulus of constant strength to the ventral root, causes this inhibitory response to increase in some cells. More often, however, the hyperpolarization caused by contraction is gradually reduced in duration and/or amplitude as the muscles are extended.

4. Even with the muscles slackened, so that they develop no tension at their ends, contraction usually produces prominent hyperpolarization of the motoneurones.

5. By passing polarizing currents or injecting chloride ions through the intracellular micro-electrode, the hyperpolarizing potentials produced by contraction of the slack and extended muscles are shown to be, at least in part, genuinely post-synaptic inhibitory events.

6. When the neurone is fired repetitively by injected current, the `silent period' in contraction corresponds to the hyperpolarization of the post-synaptic membrane.

7. Monosynaptic testing of the flexor motoneurone pool has been used to confirm the essential features of the intracellularly recorded activity.

8. Acutely spinalizing the animal increases the magnitude of the inhibitory responses caused by contraction.

9. Recordings from dorsal root fibres show that Golgi tendon organs of the ankle flexors are very sensitive to contraction and are indeed often activated by the internal forces developed in a contracting slack muscle.

10. A number of muscle spindles of the ankle flexors are activated by stimulation of the ventral root at a strength submaximal or just maximal for the α-motor fibres, despite the simultaneous unloading effect of the contracting extrafusal fibres. This spindle activation, which occurs mainly during the phase of tension development in contraction, is favoured by an increased extension of the muscle. Attempts were made to establish whether it is due to α-motor innervation of the receptors or to some mechanical interaction between the intra- and extrafusal muscle fibres.

11. The possible central and peripheral causes of the changes in motoneurone excitability produced by flexor muscle contraction are discussed. It is suggested that tendon organs of flexor muscles strongly inhibit flexor motoneurones and that α-motor innervation of muscle spindles is likely to play a more prominent role in flexors than in extensor muscles.

     

Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

Background  

Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population.