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Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 55 records · Page 3Linked to original sources

Rheumatoid factors in cystic fibrosis: associations with disease manifestations and recurrent bacterial infections.

Serum IgM and IgA rheumatoid factor (RF) levels were measured by ELISA in 71 adolescent and adult patients with cystic fibrosis (CF) and 69 control subjects. IgM RF values from 15 (21%) CF patients greater than 2 s.d. of control subjects (P less than 0.001). Elevated IgM RF values were significantly associated with worse spirometric measurements of pulmonary function (P less than 0.01) and with more frequent exacerbations of respiratory tract infection (P less than 0.001). A characteristic episodic arthropathy occurred in 27% of IgM RF positive patients, compared with 4% of IgM RF negative patients (P = 0.015). IgA RF values from 26 (37%) CF patients were elevated (P less than 0.001). Pulmonary function was significantly worse in patients with elevated IgA RF values (P less than 0.001). However, IgA RF was not associated with exacerbations of respiratory tract infection or episodic arthropathy. Both IgM and IgA RF values correlated significantly with their corresponding Ig levels, suggesting that RF synthesis was the result of polyclonal B cell activation. It is concluded that serum IgM RF values in CF are associated with worse lung disease and recurring bacterial antigenic stimulation. IgM RF may contribute to the development of arthropathy in some patients. Induction of IgA RF synthesis and its pathogenic potential may differ from IgM RF.

Adolescent

The effect of neonatal peripheral nerve section on the somadendritic growth of sensory projection cells in the rat spinal cord.

Sciatic nerve section and ligation on the day of birth results in marked growth retardation of the rat dorsal horn. This transneuronal effect was examined in spinal cord cells that project to the brain by retrograde labelling with HRP from contralateral dorso- and ventrolateral tracts in the thoracic white matter. HRP-impregnated gel pellets were implanted in the tracts for 48-72 h to allow intense somadendritic staining of the projection cells. The results show that cells in rats whose sciatic nerve has been sectioned at birth have a mean somal area that is 40% smaller than controls. Primary dendrites are reduced from a mean of 4.1 per cell to 3.1 per cell and secondary branching is reduced by 75%. The results suggest that there was no actual cell death, only growth retardation. An intact primary afferent input apparently has a strong transneuronal trophic influence on spinal cord sensory cells projecting to the brain.

Animals

The development of activity evoked by fine diameter cutaneous fibres in the spinal cord of the newborn rat.

The cutaneous afferent volley on the dorsal root was recorded in normal rat pups and in pups whose fine diameter afferents had been destroyed with capsaicin at birth. From postnatal day 2 (P2) it was possible to identify a long latency wave in the afferent volley that was reduced or absent in capsaicin treated pups and therefore attributable to A delta and C fibers. Despite this, no difference between the evoked activity of dorsal horn cells to electrical skin stimulation in normal and capsaicin treated rat pups could be detected at P2 or P5. Only at P9 was a clear long latency burst of spikes evoked in dorsal horn cells that was absent in capsaicin treated rats. The results support the idea that the postsynaptic activity evoked by small diameter A and C fibres in the rat dorsal horn in the first postnatal week is very immature.

Action Potentials

Postnatal development of the cutaneous flexor reflex: comparative study of preterm infants and newborn rat pups.

Cutaneous flexor reflex thresholds have been used as a measure of somatosensory function: the authors measured threshold in preterm infants and newborn rat pups. Preterm infants of less than 30 weeks postconceptional age (PCA) had very low thresholds of less than 1.0 g, but by 37.5+ weeks PCA thresholds were equivalent to those in normal term babies, although these are still well below adult levels. Newborn rat pups also have very low flexor reflex thresholds, which do not approach adult levels until four postnatal weeks. Repeated stimulation of the foot in preterm babies resulted in sensitization of the flexion reflex up to about 32 weeks PCA. After that age repeated stimulation resulted in habituation, as is observed in the adult. Sensitization also occurred in newborn rat pups, which changed at four postnatal weeks to habituation. The results demonstrate the sensitivity of spinal reflexes to cutaneous inputs in the neonate and it is argued that this results from lack of inhibitory control in the immature spinal cord.

Animals

Differences in the bioactivity of recombinant human TNF, LT, and T-cell-derived LT-3 on transformed cells in vitro and the Meth A tumor growing in BALB/c mice.

Cytolytic human T cells and the continuous human T cell line YM 1.2 can secrete a lymphotoxin (LT) form, termed LT-3, when stimulated in vitro. LT-3 is immunologically related to, but functionally distinct from, both alpha LT and tumor necrosis factor (TNF). Purified, native LT-3 and recombinant human LT and TNF were tested for their ability to destroy a panel of primary and continuous cell lines in vitro and cause necrosis of 8- to 9-day cutaneous Meth A tumors growing in BALB/c mice. LT-3 is more effective than either LT or TNF in inducing destruction of continuous cell lines in vitro. LT-3 induces destruction of cell lines that are resistant to both TNF and LT, and much less LT-3 is required to destroy cells that are LT and/or TNF sensitive. In contrast, none of these mediators had any measurable negative effects when tested on primary human fibroblasts. Additional studies revealed that LT-3 is also active in vivo and can cause necrosis of cutaneous Meth A tumors when administered intraperitoneally or intratumorally on BALB/c mice. LT-3 induces more rapid, consistent, and complete tumor necrosis than equivalent doses of either LT or TNF.

Animals

The postnatal development of the ventral root reflex in the rat; a comparative in vivo and in vitro study.

The ventral root reflex (VRR) and its postnatal development has been studied in vivo and in an isolated spinal cord preparation from birth up to 14 days. At postnatal days 0, 7 and 14 the VRR typically consists of an early highly synchronized peak (VRR1) and a later lower amplitude peak (VRR2). In some cases, especially at day 14 in vivo, there is a longer latency asynchronous wave (VRR3). As the age of the animal increases the latencies of the first two components VRR1 and VRR2 progressively decrease mainly due to the decrease in the central delay occurring over this period. Consideration of the central delays for VRR1 and VRR2 recorded in vivo and in vitro indicates that these waves are unlikely to be elicited by C-fibre activation and a long latency C-evoked reflex discharge equivalent to that of the adult could not be reliably recorded. Up to day 7 the appearance of the VRR was similar in both preparations but diverged in the second week of life.

Aging

Prenatal growth of fine-diameter primary afferents into the rat spinal cord: a transganglionic tracer study.

The aim of this study was to examine the growth of fine-diameter, A delta and C, primary afferents into the dorsal horn of the spinal cord. To do this, A delta and C primary afferents were transganglionically labeled with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in fetal rats at various ages and their growth was traced into the lumbar spinal cord. Sciatic or common peroneal nerves were injected with WGA-HRP at E18-E21.5 (just before birth) and the fetuses were returned to the uterus for 24 h before histochemical analysis. The results show fine-diameter afferent fibers growing into the L4/L5 spinal cord at E19 when they reach the white matter overlying the dorsal horn and begin to penetrate lamina I. Twelve hours later at E19.5 terminals can be seen in lamina IIo and by E20 they are increasing in density and have reached IIi. By birth they have achieved the density in laminae I and II that is found in the neonate and young rat. Labeling of only the peroneal branch of the sciatic nerve, leaving the tibial unlabeled, demonstrated that the somatotopic specificity of central terminal fields is apparent from the time fine afferent fibers first grow into the spinal cord.

Animals

Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors.

Two cDNA clones, lambda-CLFV-108 and lambda-CLFV-119, encoding for the beta-adrenergic receptor, have been isolated from a human brain stem cDNA library. One human genomic clone, LCV-517 (20 kb), was characterized by restriction mapping and partial sequencing. The human brain beta-receptor consists of 413 amino acids with a calculated Mr of 46480. The gene contains three potential glucocorticoid receptor-binding sites. The beta-receptor expressed in human brain was homology with rodent (88%) and avian (52%) beta-receptors and with porcine muscarinic cholinergic receptors (31%), supporting our proposal [(1984) Proc. Natl. Acad. Sci. USA 81, 272 276] that adrenergic and muscarinic cholinergic receptors are structurally related. This represents the first cloning of a neurotransmitter receptor gene from human brain.

Amino Acid Sequence

Cutaneous primary afferent properties in the hind limb of the neonatal rat.

1. Single cutaneous primary afferent units innervating the hind limb were recorded from the L4 dorsal root ganglion in neonatal rats aged 0-14 days. 2. Conduction velocities were less than 1.0 m s-1 on day 0 but by day 1 had clearly divided into a faster conducting group whose velocities markedly increased with age, reaching 15 m s-1 on day 14, and a slower conducting group that increased only slightly to 1.5 m s-1 on day 14. 3. All major cutaneous receptor types could be identified from day 0. Slowly adapting and rapidly adapting touch and hair mechanoreceptors had the same response patterns and thresholds described for such receptors in the adult, but peak firing frequency and ability to follow high frequency electrical stimulation was low. At birth, these afferents could only follow 20 Hz stimuli but by day 14 this had increased to 200 Hz. 4. Nociceptors were also present from birth. Polymodal nociceptors responding to intense mechanical, thermal and chemical skin stimulation were completely mature in their firing frequencies and response patterns from day 0. High threshold mechanoreceptors responded at somewhat lower frequencies than the adult but otherwise were comparable. 5. A prominent group of receptors responding to firm pressure on the skin were observed in the first post-natal week but not on day 14. It is proposed that these may represent maturing touch or hair receptors or alternatively a group of temporary receptors that are lost during development. 6. On the first post-natal days, there was no relation between conduction velocity and receptor type. After this time, however, afferents which have A beta fibres in the adult tended to conduct faster in the neonate than those with A delta and C fibres. There were exceptions however demonstrating that receptor properties and afferent axons do not always mature in parallel. 7. These results show that considerable maturation of cutaneous receptors must occur before birth. They suggest that central rather than peripheral maturation is responsible for the post-natal changes in dorsal horn physiology and cutaneous sensory reflexes. Furthermore since C polymodal nociceptors are fully functional at birth, the delayed development of neurogenic oedema and of certain specific C-evoked reflexes could be due to slow maturation of critical chemical factors in C fibres.

Adaptation, Physiological

An evaluation of a glass ionomer luting agent: pulpal histological response.

Pulpal histological response after crown cementation with a glass ionomer luting agent was evaluated and compared with the response to a polycarboxylate cement or a varnish plus zinc phosphate cement. Pulpal histological response was evaluated on teeth that had full crowns cemented with the test luting agents 3, 10, and 56 days after cementation. No statistically significant differences were found in pulpal histological response between the materials tested during all periods. These findings suggest that factors other than pulpal inflammation are contributing to the reported hypersensitivity after cementation associated with glass ionomer luting agents.

Animals

An evaluation of a glass ionomer luting agent: bacterial leakage.

This study quantitatively evaluates the bacterial leakage beneath crowns cemented with a glass ionomer cement compared with those cemented with a polycarboxylate cement or a varnish plus zinc phosphate cement. Bacterial samples were taken from beneath full crowns cemented with the test luting agents 3, 10, and 56 days after cementation. Two-way analysis of variance of the resultant data showed a significant increase in bacterial counts for zinc phosphate, a significant decrease for polycarboxylate, and no change for glass ionomer. These findings suggest that bacterial leakage may not be the reason for the reported poor clinical response associated with glass ionomer luting agents.

Bacteria