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Biomedical subjects

M Fitzgerald

Publications and source records attributed to M Fitzgerald.

At least 199 records · Page 11Linked to original sources

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↗

Episodic arthropathy in adult cystic fibrosis.

Five (8.5 per cent) of 59 adult patients with cystic fibrosis described a characteristic arthropathy which was episodic, self-limiting and polyarticular, affecting large and small peripheral joints without evidence of progression to joint damage. The five patients with arthropathy did not differ from the remaining 54 with respect to manifestations of cystic fibrosis. Synovial fluid obtained from two patients during acute episodes was clear, viscous and contained no cells. Biopsies of synovial membrane from the same patients demonstrated prominent congested blood vessels with some synovial oedema, but no evidence of inflammation. Immunofluorescent staining of synovial membrane demonstrated characteristic intimal deposition of immunoglobulin in the vessels. In one of the two patients acute arthropathy was accompanied by transient cutaneous vasculitis, circulating immune complexes and lowered serum complement levels, which suggests that the episodic arthropathy in at least some patients with cystic fibrosis is mediated by an immune mechanism.

Adolescent↗

Somatotopic organization of cutaneous afferent terminals and dorsal horn neuronal receptive fields in the superficial and deep laminae of the rat lumbar spinal cord.

The somatotopic organization of A- and C-afferent fibre terminals in the dorsal horn of the rat lumbar spinal cord was compared with the spatial location of second-order dorsal horn neuronal mechanoreceptive fields. The central terminal fields of the sural, saphenous, and tibial nerve were mapped by labelling the nerves with horseradish peroxidase (HRP). A previous study used the transganglionic transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) to produce a somatotopic map of high-threshold C-fibre terminal fields in lamina II (Swett and Woolf: J. Comp. Neurol. 231:66-77, '85). In the present study the terminal fields of low-threshold A beta afferents that terminate in laminae III and IV were mapped by using unconjugated HRP at prolonged survival times (72 hours). Unfixed tissue was used to increase the sensitivity of the tetramethylbenzidine reaction, thus allowing these afferent terminals to be clearly seen. The general spatial arrangement of the terminal fields in laminae III/IV closely resembled that found in lamina II in the mediolateral and rostrocaudal planes but because of a dorsoventral obliquity of the afferent terminals, the superficial and deeper fields are not in strict vertical register. The input to laminae II-IV of the dorsal horn may therefore be viewed as two horizontally arranged sheets of afferent terminals both accurately representing the skin surface, the more superficial sheet representing the high-threshold C-afferents and the deeper sheet, low-threshold A-beta afferents. The spatial organization of high-threshold A-delta afferents in laminae I and V appears to be quite different, with a transverse rather than a longitudinal orientation. To study dorsal horn cell receptive field organization two single units with mechanoreceptive fields were recorded extracellularly in each of 87 vertical tracks in the lumbar spinal cord, one unit in the superficial dorsal horn and the second in the deep dorsal horn. In general the somatotopic organization of the receptive fields of both sets of units followed that of the afferent terminal fields but there were cells with receptive fields that were anomalous relative to the recording site. No evidence of any vertical relation or columnar arrangement in receptive field size, threshold, or location on the body surface was found when comparing the two units in a pair. Furthermore, no laminar functional specialization was found, the majority of neurones having both low- and high-threshold inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

The functional development of descending inhibitory pathways in the dorsolateral funiculus of the newborn rat spinal cord.

The postnatal development of descending inhibition in the spinal cord has been studied in the rat. Electrophysiological recordings were made in neonatal rat pups of the activity in single lumbar dorsal horn cells evoked by stimulation of the skin of the hindlimb. Descending inhibition was tested by observing the effect of stimulation of the dorsolateral funiculus (DLF) at thoracic level on the dorsal horn cell responses. In adults the DLF is known to contain descending axons from the brainstem which inhibit dorsal horn cell activity. Such inhibition was always observed in days 22-24 rat pups. At 18 days of age it was present but required higher-intensity stimulation to produce an effect. On day 12 only half the dorsal horn cells tested were inhibited by DLF stimulation and then only weakly. On day 9 no cells were inhibited. Application of horseradish peroxidase to DLF axons in the lumbar cord resulted in retrograde labelling of cells in the medulla, pons and midbrain. The labelling on day 6 was comparable to the adult. The results show that despite the early anatomical existence of a descending DLF pathway, there is no functional descending inhibition until days 10-12 of life. It is suggested that this is due to delayed maturation of crucial interneurones in the dorsal horn or to insufficient levels of 5-hydroxytryptamine or other neurochemicals in the descending DLF axon terminals.

Aging↗

The relationship between the dentist's year of graduation and ordering of bitewing radiographs.

This article reports the results of a survey of general practice dentists on the relationship of the dentist's year of graduation to the ordering of bitewing radiographs for patients. More recent graduates were more likely to indicate ordering the radiographs at 6-month intervals. There were no differences in ordering associated with the dentist's experience. Shorter intervals between ordering were indicated by all dentists for patient groups at high risk of caries.

Adolescent↗

The sprouting of saphenous nerve terminals in the spinal cord following early postnatal sciatic nerve section in the rat.

Transganglionic labelling of the saphenous nerve in rats with WGA-HRP revealed the central distribution of its terminals in the lumbar dorsal horn. The terminal field was clearly defined and consistent in rats aged between day 6 and day 90. If, however, the sciatic nerve was sectioned on day 1 of postnatal life, the saphenous terminal field expanded to occupy twice the normal area (measured between the L2 and L4 boundaries). The spread was caudal, medial, and lateral into areas normally occupied by sciatic nerve terminals. This sprouting was very weak if the sciatic nerve was sectioned later in postnatal life, on day 5, and nonexistent if sectioning took place on day 10. Crushing the sciatic nerve on day 1 also triggered the effect but the spread of the terminal field was less than that produced by section of the sciatic nerve. There was no evidence of sprouting from the contralateral intact sciatic nerve. The results demonstrate the necessity of intact afferent input during a critical period of neonatal life in order to maintain the precise somatotopic termination pattern of dorsal root afferents.

Aging↗

Plasticity of acid phosphatase (FRAP) afferent terminal fields and of dorsal horn cell growth in the neonatal rat.

Peripheral nerve section results in depletion of fluoride-resistant acid phosphatase (FRAP) from the nerve terminals in the dorsal horn of the spinal cord (Schoenen et al., '68) and this has been used in the past to map the termination field of individual nerves (Rustioni et al., '71; Devor and Claman, '80). In the present study we show that a similar central depletion occurs following sciatic nerve section or crush in neonatal rats. Unlike adults, however, the area of depletion is rapidly filled by sprouting of FRAP-containing afferent terminals from nearby intact peripheral nerves. The sprouting is extensive but never completely fills the depleted area. After nerve crush there is some recovery of FRAP from the sciatic nerve terminals themselves as well as from nearby nerve terminals. The source of recovered FRAP is demonstrated by resectioning or recrushing the nerves. The sprouting occurred when the sciatic was injured on day 1 but failed to take place when the injury was applied on or after day 10. Sciatic nerve section on day 1 also produces marked growth retardation of the ipsilateral dorsal horn gray matter that becomes more apparent as the rat matures. Nerve crush produces a less marked shrinkage that is slower in onset. If the nerve is crushed repeatedly, however, so that regeneration is prevented, the shrinkage is analogous to that following nerve section. No shrinkage occurs if the nerve is cut or crushed on day 10. The results show that separation of the spinal cord from its peripheral input at a critical stage in development results in disruption of the somatotopic organization of the C fibre afferent input to the dorsal horn and in slowing of growth of the dorsal horn gray matter.

Acid Phosphatase↗