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Biomedical subjects

K G Smith

Publications and source records attributed to K G Smith.

At least 55 records · Page 3Linked to original sources
PubMed1995

FAS is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen.

In establishing the memory B-cell population and maintaining self-tolerance during an immune response, apoptosis mediates the removal of early, low-affinity antibody-forming cells, unselected germinal center (GC) cells, and, potentially, self-reactive B cells. To address the role of the apoptosis-signaling cell surface molecule FAS in the B-cell response to antigen, we have examined the T-cell-dependent B-cell response to the carrier-conjugated hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) in lpr mice in which the fas gene is mutated. High levels of FAS were expressed on normal GC B cells but the absence of FAS did not perturb the progressive decline in numbers of either GC B cells or extrafollicular antibody-forming cells. Furthermore, the rate of formation and eventual size of the NP-specific memory B-cell population in lpr mice were normal. The accumulation of cells with affinity-enhancing mutations and the appearance of high-affinity anti-NP IgG1 antibody in the serum were also normal in lpr mice. Thus, although high levels of FAS are expressed on GC B cells, FAS is not required for GC selection or for regulation of the major antigen-specific B-cell compartments. The results suggest that the size and composition of B-cell compartments in the humoral immune response are regulated by mechanisms that do not require FAS.

Amino Acid Sequence↗
PubMed1995

The effect of delayed nerve repair on the properties of regenerated fibres in the chorda tympani.

The characteristics of regenerated fibres in the chorda tympani have been investigated in cats after nerve section without repair or after section followed by nerve repair twelve weeks later. In the unrepaired group the animals were allowed to recover for twenty four weeks and after delayed repair there was a further recovery period of twelve or twenty four weeks. The properties of gustatory, thermosensitive and mechanosensitive units and the return of vasomotor and secretomotor responses were then investigated and data compared with that from normal controls and from animals which had undergone immediate nerve repair. After nerve section, integrated whole-nerve activity recorded from the chorda tympani during gustatory or thermal stimulation of the tongue was reduced when compared to controls, but there were only small differences between the repaired and unrepaired groups. Recordings made from single units in the chorda tympani revealed that more units were spontaneously active after repair (P < 0.05) and the gustatory units produced more impulses when stimulated (P < 0.005). Twelve weeks after delayed repair the units had slower conduction velocities than those in the unrepaired nerves (P < 0.001), but by twenty four weeks after repair they were significantly faster (P < 0.05). There was little difference in the level of recovery twelve weeks after immediate or delayed repair. We conclude that delayed nerve repair results in better recovery than leaving the nerve unrepaired and that a twelve week delay before repair has little effect.

Animals↗
PubMed1995

Soluble antigen can impede affinity maturation and the germinal center reaction but enhance extrafollicular immunoglobulin production.

The primary immune response to T cell-dependent Ags develops in two pathways. These comprise the extrafollicular pathway, in which foci of Ab-secreting cells develop, and the intrafollicular pathway that gives rise to germinal centers and affinity maturation. We have previously shown that de-aggregated (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to the protein carrier human serum albumin (HSA), (NP-HSA), injected 6 days after challenge immunization with aggregated NP-HSA, resulted in impaired development of NP-specific, higher-affinity cells. Studies presented here describe the cellular basis underlying this impairment of affinity maturation. Using multiparameter flow cytometry, we show that mice injected with soluble NP-HSA ("tolerant" mice) develop significantly fewer NP-binding IgG1+ B220+ cells of germinal center origin than do the control ("immune") mice. In addition, using immunohistology, we noted that the spleens of tolerant mice had a marked reduction in the number of germinal centers that contained lambda-bearing cells, these being characteristic of the NP response in C57BL/6 mice. Curiously, germinal centers in the spleens of tolerant mice had more than twice the volumes of those in the immune spleens. In contrast to its effect on the germinal center pathway, soluble Ag enhanced the extrafollicular pathway, reflected by the increased numbers of B cells secreting IgM and IgG1 Abs specific for NP, HSA, and undefined Ags. Thus, soluble NP-HSA given after challenge immunization can impede affinity maturation of NP-specific cells, but enhance the extrafollicular pathway. These results are discussed in the context of the known capacity of some persisting Ags, e.g., malaria parasites, to frustrate affinity maturation and memory cell generation.

Animals↗
PubMed1995

Soluble antigen can cause enhanced apoptosis of germinal-centre B cells.

Germinal centres are dynamic microenvironments of B-lymphocyte differentiation, which develop in secondary lymphoid tissues during immune responses. Within germinal centres, activated B lymphocytes proliferate and point mutations are rapidly introduced into the genes encoding their immunoglobulin receptors. As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen. Immunoglobulin gene mutation can also lead to reactivity to self antigens. It has been suggested that any newly formed self-reactive B cells are eliminated within the germinal centre in order to avoid autoimmunity. Here we present evidence that antigen-specific, high-affinity, germinal-centre B cells are rapidly killed by apoptosis in situ when they encounter soluble antigen. The effect seems to act directly on the B cells, rather than through helper T cells. Furthermore, the apoptosis is unique to germinal-centre cells, and is only incompletely impeded by constitutive expression of the proto-oncogene bcl-2. This phenomenon may reflect clonal deletion of self-reactive B cells within germinal centres.

Animals↗
PubMed1995

The reinnervation of the tongue and salivary glands after two methods of lingual nerve repair in the cat.

The recovery of fibres in the chorda tympani after repair by epineurial suture or entubulation was investigated. The combined trunk of the chorda tympani and lingual branch of the trigeminal nerve was sectioned unilaterally, repaired using either epineurial sutures or entubulation, and allowed to recover for 12 weeks. The properties of gustatory, thermosensitive and mechanosensitive units, and the return of vasomotor and secretomotor responses were then investigated. After repair by epineurial suture, integrated whole-nerve activity recorded from the chorda tympani during stimulation of the tongue with gustatory or thermal stimuli was reduced in all areas of the tongue when compared to controls. After entubulation repair, little or no activity could be recorded. Recordings made from 57 single units in the chorda tympani after repair by epineurial suture revealed a greater proportion of purely mechanosensitive units and fewer gustatory units than in the controls. Fewer units were spontaneously active, they had lower maximum discharge frequencies, and produced fewer impulses when stimulated. Recordings made from 61 single units after repair by entubulation revealed receptor characteristics with greater differences from controls than after epineurial suture and there was only one gustatory and one thermosensitive unit. Vasomotor responses were completely restored after repair by epineurial suture, but some responses were smaller after entubulation repair. Secretomotor responses were significantly smaller after both methods of repair and there was no difference between the two groups.

Action Potentials↗
PubMed1995

An experimental study of lingual nerve repair using epineurial sutures or entubulation.

The recovery of the mechanosensitive afferent fibres in the lingual branch of the trigeminal nerve has been studied using electrophysiological techniques in cats, after two methods of nerve repair. After nerve section the lingual nerve was repaired by either epineurial sutures or by entubulation. 12 weeks after either method of repair the properties of the regenerated fibres were significantly different from normal, but following repair with epineurial suture they were closer to normal than after repair by entubulation. After entubulation the fibres had a greater reduction in conduction velocity, a greater increase in force threshold, and the adaptation times were faster. The results suggest that epineurial suture should be preferred clinically.

Animals↗
PubMed1995

An experimental study of three methods of lingual nerve defect repair.

PURPOSE: This study compares three methods of lingual nerve defect repair. MATERIALS AND METHODS: The recovery of the mechanosensitive and thermosensitive afferent fibers in the lingual branch of the trigeminal nerve in cats was studied using electrophysiological techniques 24 weeks after the removal of a segment of lingual nerve and repair of the defect by one of three methods. The nerve gap was closed by either stretching the nerve ends together and repairing under tension, insertion of a sural nerve graft, or use of a freeze-thawed muscle graft. The characteristics of the regenerated fibers were investigated and the data were compared with that from normal control animals. RESULTS: After nerve repair, integrated whole-nerve activity evoked by thermal (cold) stimulation of the tongue was smaller than in the controls, but there were no differences between the repaired groups. However, recordings made from single axons in filaments dissected from the nerve revealed differences between the groups; the units were less sensitive after either method of grafting than after stretch repair. CONCLUSIONS: It is concluded that repair of a short gap in the lingual nerve by stretch repair with an end-to-end anastomosis, even with some degree of tension, is followed by better recovery than by grafting. However, where a graft is necessary, a similar level of recovery will result from use of a frozen muscle graft or a sural nerve graft.

Action Potentials↗
PubMed1995

An experimental study on the recovery of the lingual nerve after injury with or without repair.

The recovery of the mechanosensitive and thermosensitive afferent fibres in the lingual branch of the trigeminal nerve has been studied using electrophysiological techniques in cats after nerve section without repair or after section followed by nerve repair 12 weeks later. In the unrepaired group, recovery was permitted for 24 weeks, and after delayed repair there was a further recovery period of either 12 or 24 weeks. The characteristics of the regenerated fibres were then investigated, and data were also compared with those from normal control animals and from animals which had undergone immediate nerve repair. The results revealed only small differences between the repaired and unrepaired groups and it is concluded that delayed repair of a clean transection site results in only slightly better recovery than leaving the nerve unrepaired. It is also concluded that a 12-week delay before repair has little detrimental effect.

Adaptation, Physiological↗
PubMed1995

Metastatic endophthalmitis in dialysis patients.

Metastatic bacterial endophthalmitis is a rare but devastating complication of septicaemia. We present 3 recent cases occurring in dialysis patients. Septicaemic dialysis patients seem particularly prone to staphylococcal endophthalmitis which developed in the face of therapeutic serum concentrations of appropriate antibiotics in all 3 cases. Prompt treatment, including consideration of intravitreal antibiotics, is required if vision is to be preserved. Early signs of endophthalmitis should be actively sought in septicaemic dialysis patients, as they are easily overlooked.

Adult↗
PubMed1995

The re-innervation of the tongue and salivary glands after lingual nerve repair by stretch, sural nerve graft or frozen muscle graft.

The lingual nerve is sometimes injured during the surgical removal of impacted third molar teeth and may require repair. Removal of the damaged section of nerve prior to repair leaves a gap between the nerve ends, and we have investigated methods of closing the gap. THe characteristics of regenerated fibers in the chorda tympani have been recorded in cats 24 weeks after the removal of a segment of lingual nerve and repair of the defect by three methods. The nerve gap was closed either by stretching the nerve ends together and repairing under tension, or by the insertion of a sural nerve graft or freeze-thawed muscle graft. The properties of gustatory, thermosensitive, and mechanosensitive units and the return of the vasomotor and secretomotor responses were investigated by electrophysiological techniques and the data from each of the repair groups compared with those obtained from a series of normal control animals. After each method of repair, the integrated whole-nerve activity recorded from the chorda tympani during gustatory or thermal stimulation of the tongue was reduced when compared with controls, but there was little significant difference between the repair groups. Recordings made from single units in the chorda tympani revealed that conduction velocities were faster after stretch repair than after sural nerve graft or frozen muscle graft. In addition, 48% of the units had developed into principally gustatory units after stretch repair, indicating a better level of recovery than in the graft groups, which contained 33% and 32%, respectively. The secretomotor responses were also significantly greater after stretch repair than in either of the graft groups or the controls, but there was no difference in the vasomotor responses. These results reveal that repair of a short gap in the lingual nerve by stretching the ends together is followed by better overall recovery than after grafting, but where a graft is used, a similar level of recovery results from use of a frozen muscle graft or a sural nerve graft.

Anastomosis, Surgical↗
PubMed1994

Bcl-2 increases memory B cell recruitment but does not perturb selection in germinal centers.

To address the role of apoptosis in the humoral immune response, we have examined a well-characterized T cell-dependent B cell response in mice expressing transgenic Bcl-2 in their B lymphocytes. The selection of somatic mutants and the appearance of high affinity antibodies was not affected by constitutive Bcl-2 expression. Such expression did, however, disproportionately increase the antigen-specific memory B cell pool, suggesting that the final size of the memory compartment may be regulated by an apoptotic process, which, in turn, can be influenced by Bcl-2. In addition, transgenic mice showed prolonged survival of foci of early antibody-producing cells, suggesting their removal is mediated by apoptosis that can be blocked by Bcl-2.

Animals↗
PubMed1994

Critical pathways.

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Clinical Protocols↗
PubMed1993

The potential for elderly donors to increase renal transplantation rates in Australia.

OBJECTIVE: To estimate the potential increase in renal donation rates if elderly donors (those over 60 years of age) were considered. DESIGN: Patients dying from acute brain damage resulting from stroke were identified using the Royal Melbourne Hospital (RMH) Stroke Service Register. Their records were retrospectively analysed to assess their eligibility as potential renal donors. SETTING: One hundred and ninety-eight patients dying from acute brain damage caused by stroke at a large metropolitan teaching hospital (RMH), from May 1987 to December 1990 inclusive. PATIENT ASSESSMENT: Patients were considered "eligible", "ineligible" or "possibly eligible" (requiring further assessment) as donors according to existing strict criteria (see methods) but irrespective of age. RESULTS: Of 198 stroke patients dying of brain damage, 92 satisfied the criteria of eligibility for renal donation; 51 of these were over 60 years old, yet only one became a renal donor. CONCLUSION: There is good evidence that elderly donors are acceptable for renal transplantation, yet they are not being referred. The consideration of elderly stroke victims as renal donors could have a dramatic effect on decreasing transplant waiting lists, increasing recipient patient well-being, and reducing hospital costs.

Adult↗
PubMed1992

Augmentin-induced jaundice with a fatal outcome.

OBJECTIVE: To report a case of death due to Augmentin-induced cholestatic hepatitis and discuss a possible drug interaction between Augmentin and oestrogenic steroids. CLINICAL FEATURES, INTERVENTION AND OUTCOME: An 81-year-old man, on oestrogen therapy for prostatic malignancy, presented with obstructive jaundice one week after completing a four-week course of Augmentin for recurrent urinary tract infection. Liver biopsy showed features of a drug-induced cholestatic hepatitis with bile duct injury. His clinical course was marked by progressive deterioration with increasing jaundice and the development of hepatic encephalopathy. A course of prednisolone did not result in any improvement and he died nine weeks after the onset of jaundice. CONCLUSIONS: The cholestatic hepatitis induced by Augmentin is usually reversible but may be progressive, leading to death. The concurrent administration of ethinyloestradiol, a potentially cholestatic agent, may have altered the susceptibility and/or course of the reaction in this patient.

Aged↗