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L A Stark

Publications and source records attributed to L A Stark.

7 recordsLinked to original sources
PubMed1994

Accumulation of p53 is associated with tumour progression in cutaneous lesions of renal allograft recipients.

Renal allograft recipients suffer from a markedly increased susceptibility to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the associated genetic events. In this study we initially employed immunocytochemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent controls. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignant keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma differed significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (an older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of squamous cell carcinomas. These differences were not statistically significant. Morphologically, p53 immunoreactivity strongly associated with areas of epidermal dysplasia and the abundance of staining correlated positively with the severity of dysplasia. These data suggest that p53 plays a role in skin carcinogenesis and is associated with progression towards the invasive state. No correlation was observed between accumulated p53 and the presence of human papillomavirus (HPV) DNA in any of the lesions. Single-strand conformational polymorphism analysis (exons 5-8) was used to determine the frequency of mutated p53 in 28 malignancies with varying degrees of immunopositivity. p53 mutations were found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained and none where < 10% of cells were stained. These data imply that factors other than p53 gene mutation play a part in accumulation of p53 in skin cancers.

Adolescent↗
PubMed1994

Prevalence of human papillomavirus DNA in cutaneous neoplasms from renal allograft recipients supports a possible viral role in tumour promotion.

It is well established that renal allograft recipients (RARs) have an increased incidence of viral warts and premalignant and malignant cutaneous lesions, and the risk of their development increases in proportion to duration of graft survival. It has been postulated that, in addition to the effects of prolonged immunosuppression and previous sun exposure, human papillomaviruses (HPV) may also contribute to the carcinogenic process. In this study, the prevalence of HPV DNA was examined in a range of premalignant and malignant cutaneous tumours from 50 immunosuppressed patients (47 renal allograft recipients plus three cardiac allograft recipients) and 56 immunocompetent patients using Southern hybridisation as a low-stringency screening method and type-specific polymerase chain reaction (PCR) assays for eight HPV types. The combined results for renal allograft recipients show that HPV DNA was detectable in 79% of viral warts, 42% of premalignant keratoses, 33% of intraepidermal carcinomas, 43% of invasive squamous cell carcinomas and 16% of uninvolved skin specimens (squamous cell carcinomas/renal allograft recipients significantly different at P < 0.05 from uninvolved skin specimens/renal allograft recipients). In immunocompetent patients the pattern of HPV DNA prevalence was 100% for viral warts; 25% for keratoses, 23% for intraepidermal carcinomas, 22% for squamous cell carcinomas and 8% for uninvolved skin. No single HPV type predominated in tumour specimens from either group. More tumours were found to contain HPV DNA by Southern hybridisation analysis than PCR, indicating the presence of HPV types other than HPV 1, 2, 5, 6, 8, 11, 16 and 18 in some tumours. However, 'low cancer risk' HPV types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were specifically detected by PCR in a small number of neoplasms. These data suggest that multiple HPV types may contribute to cutaneous neoplasia in RARs and that they appear to act early in the process of carcinogenesis, perhaps by functioning as tumour promoters via stimulation of cell proliferation.

Adult↗
PubMed1986

Response properties of neurons in the lateral geniculate nucleus of neonatal kittens.

A previous study led us to consider the implications of the types of receptive fields found in the lateral geniculate nucleus (LGN) of neonatal kittens. Thus, we studied cells in the A layers in the LGN of kittens aged 6-29 days using extracellular recording techniques. Peri-stimulus-time-histograms were constructed in response to flashing spots of light centered in the receptive field of each unit. All units studied showed an excitatory response only to light onset (on-center) or light offset (off-center). No units were found which had an excitatory response to both phases of the stimulus (On-Off). Possible differences in classification between this study and that of earlier workers who reported On-Off cells in young kittens are discussed.

Action Potentials↗
PubMed1986

A role for action-potential activity in the development of neuronal connections in the kitten retinogeniculate pathway.

The role of action potentials in the development of proper synaptic connections in the mammalian CNS was studied in the kitten retinogeniculate pathway. Our basic finding is that there is improper segregation of retinal inputs onto LGN cells after prolonged retinal action-potential blockade. Retinal ganglion cell firing was silenced from birth by repeated monocular injections of TTX. The resulting ganglion cell connections in the LGN were studied electrophysiologically after the action-potential blockade was ended. Most cells in the deprived LGN layers received excitatory input from both ON-center and OFF-center type ganglion cells, whereas LGN cells normally receive inputs only from ON-center or OFF-center ganglion cells, but not from both types. Improper segregation of ON and OFF inputs has never been reported after other types of visual deprivation that do not block ganglion cell activity. Control experiments showed that receptive fields in the nondeprived LGN layers were normal, that ganglion cell responses remained normal, and that there was no obvious ganglion cell loss. We also showed that individual LGN cells with ON and OFF excitatory inputs were not present in normal neonatal kittens. Two other types of improper input segregation in response to action-potential blockade were also found in the deprived LGN layers. (1) A greater than normal number of LGN cells received both X- and Y-type ganglion cell input. (2) Almost half of the cells at LGN layer borders were excited binocularly. Recovery of LGN normality was rapid and complete after blockade that lasted for only 3 weeks from birth, but little recovery was seen after about 11 weeks of blockade. The susceptibility to action-potential blockade decreased during the first 3 postnatal weeks. These findings may result from axon-terminal sprouting or from the failure of axon terminals to retract. The results are consistent with the idea that normally synchronous activity of neighboring ganglion cells of like center-type may be used in the refinement of retinogeniculate synaptic connections.

Action Potentials↗
PubMed1982

Abnormal development of kitten retino-geniculate connectivity in the absence of action potentials.

Action potentials were silenced in one eye of neonatal kittens by repeated intraocular injections of tetrodotoxin for 5 to 8 weeks. After tetrodotoxin blockade was allowed to wear off, receptive field properties of individual relay cells in the lateral geniculate nucleus were examined. The many ON-OFF and binocular fields found in the layers that receive input from the treated eye suggest that these cells had extremely abnormal retino-geniculate synaptic connections. These effects were different in kind from those seen after deprivation rearing that does not silence action potentials. Lack of action potential activity was concluded to lead to abnormal development in the central nervous system.

Action Potentials↗
PubMedDate not supplied

Elimination of action potentials blocks the structural development of retinogeniculate synapses.

Although the influence of electrical activity on neural development has been studied extensively, experiments have only recently focused on the role of activity in the development of the mammalian central nervous system (CNS). Using tetrodotoxin (TTX) to abolish sodium-mediated action potentials, studies on the visual system show that impulse activity is essential both for the normal development of neuronal size and responsivity in the lateral geniculate nucleus (LGN), and for the eye-specific segregation of geniculo-cortical axons. There have been no anatomical studies to investigate the influence of action potentials on CNS synaptic development. We report here the first direct evidence that elimination of action potentials in the mammalian CNS blocks the growth of developing axon terminals and the formation of normal adult synaptic patterns. Our results show that when TTX is used to eliminate retinal ganglion-cell action potentials in the cat from birth to 8 weeks, the connections made by ganglion cell axons with LGN neurones, retinogeniculate synapses, remain almost identical morphologically to those in the newborn kitten.

Action Potentials↗