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J Nicholls

Publications and source records attributed to J Nicholls.

At least 109 records · Page 6Linked to original sources
PubMed1989

Steps in the development of chemical and electrical synapses by pairs of identified leech neurons in culture.

Experiments have been made to follow the development of chemical and electrical transmission between pairs of leech neurons in culture. 1. The cell bodies of identified neurons were isolated from the CNS by suction after mild enzyme treatment, together with a length of the initial segment (or 'stump'). The neurons tested were Retzius cells (R), annulus erector motoneurons (AE), Anterior pagoda cells (AP) and pressure sensory cells (P). Pairs of cells were placed together in various configurations, with different sites on their surfaces making contact. 2. When pairs of Retzius cells were apposed with their stumps touching, serotonergic, chemically mediated synaptic transmission became apparent before electrical transmission. By 2.5 h impulses in either of the two Retzius cells produced hyperpolarizing inhibitory potentials in the other. These potentials were reversed by raised intracellular Cl and showed clear facilitation. The strength of chemical transmission between Retzius cells increased over the next 72 h. 3. After chemical transmission had been established, weak non-rectifying electrical transmission became apparent between Retzius cells at about 24-72 h. By 4 days coupling became stronger and tended to obscure chemically evoked synaptic potentials. 4. When pairs of Retzius cells were aligned in culture with the tip of one cell stump touching the soma of the other, chemical transmission also developed rapidly. Transmission was, however, in one direction, from stump to soma. At later stages non-rectifying electrical coupling developed as with stump-stump configuration. With the cell bodies of two Retzius cells apposed, electrical coupling developed after several days, before chemical transmission could be observed. 5. When Retzius and P cells were cultured with their stumps in contact, inhibitory chemical synaptic transmission developed within 24 h. Transmission was always in one direction, from Retzius to P cell. Electrical coupling of Retzius and P cells never occurred whatever the spatial relations of the cells to one another. 6. Annulus erector motoneurons, which contain ACh and a peptide resembling FMRFamide, first developed electrical coupling when the two stumps were in contact and then, later, bi-directional chemical transmission. Anterior Pagoda pairs placed stump-to-stump showed electrical connections. 7. Electronmicrographs revealed the presence of synaptic structures within 24 h after Retzius-Retzius, Retzius-P or AE-AE stumps were apposed. 8. The specificity of connections between cultured cells was similar to that observed in earlier experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Of mice and men--data capture in the clinical environment.

We have considered the problem of data capture in the critical care area. Review of previous work on the use of alternative input devices for speed and accuracy of data entry yields conflicting information but suggests that requirements depend on input task, data type and skill of the user. We have performed comparative studies of the QWERTY keybord, cursor control keys, mouse and graphics tablet for data entry in two intensive therapy unit (ITU) environments. The graphics tablet proved overall the best of the devices studied. We report the potential applications of this type of input device.

Computer Systems↗
PubMed1989

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗
PubMed1989

Intensive induction chemotherapy for poor risk non-seminomatous germ cell tumours.

An increase in initial chemotherapy intensity was evaluated in 29 patients with high risk metastatic non-seminomatous germ cell tumours (NSGCT) of the testis, defined by the presence of multiple large lung metastases, liver, bone or brain metastases, or the combination of large abdominal mass with high serum concentration of the tumour markers alpha-foetoprotein (AFP) or beta subunit of human chorionic gonadotrophin (HCG) (AFP greater than 500 ku/l or HCG greater than 1000 iu/l). Four courses of bleomycin, vincristine and cisplatin (BOP) were given at 7 day intervals, followed by three courses of etoposide, cisplatin with or without bleomycin (BEP or EP) at 21 day intervals for a total of 13 weeks of chemotherapy. Twenty-three (85%) of 27 evaluable patients have remained continuously free from disease progression at a median of 24 months (range 14-38 months) from chemotherapy and the actuarial 2 year freedom from progression rate is 86% (95% CI = 73-99%). Three patients died from non-malignant causes, two of bleomycin pneumonitis and one from complications of cystic fibrosis. Thus cause specific overall survival in the total population of treated patients is 79%. With appropriate limitation of bleomycin dosage, this approach is well tolerated and results compare favourably with less intensive induction schedules based on initial 21-28 day cycles.

Adolescent↗
PubMed1989

Young children's understanding of counting and cardinality.

4-year-old's knowledge of counting and cardinality--the last count word reached represents the numerosity of the set--was tested in 2 experiments. Experiment 1 investigated the nature of early cardinality responses by presenting different forms of the cardinality question before, after, and before and after the child counted. Both type and time of question has large effects. Experiment 2 examined whether children of this age could recognize errors in 4 counting procedures and whether they would reject a cardinality response arrived at through a mistaken counting procedure. The children were very good at recognizing a standard counting procedure as correct. They had only limited success at treating procedures that violated the stable order of count words or violated the one-one correspondence between count word and object as incorrect. They lacked an understanding of the order irrelevance in that they judged valid, nonstandard counting orders as incorrect. The children did not seem to link their evaluation of a cardinality response with their evaluation of the counting procedure used to reach that response. The results do not indicate that counting principles initially govern the child's acquisition of counting knowledge. They are consistent with the suggestion that early cardinality responses are last-word responses.

Child, Preschool↗
PubMed1988

Hepatic granulomas: a 15-year experience in the Royal Adelaide Hospital.

The clinical and pathological associations of hepatic granulomas in patients who presented to the Royal Adelaide Hospital between January 1, 1968 and February 29, 1984 were reviewed retrospectively. Cases of primary biliary cirrhosis were excluded. Of 59 patients with hepatic granulomas, clear associations with diseases were identified in 42 (71%) patients. These were sarcoidosis (seven cases), chronic liver disease (12 cases), biliary tract disease (three cases), tuberculosis (four cases), Q-fever (three cases), other infections (four cases), drug hypersensitivity (four cases) and neoplasms (five cases). Ten patients had multiple associations and five other patients presented without any clearly defined cause for granulomas. Three of these latter patients presented with an acute febrile illness, showed hepatomegaly and had abnormal results of liver function tests. These cases may represent the entity that is labeled "idiopathic granulomatous hepatitis". Two other patients abused alcohol. Granulomas were categorized morphologically as microgranulomas, macrogranulomas and lipogranulomas according to their size, organization and the presence of fat droplets. Microgranulomas were associated with diseases of short duration and less architectural disturbance of the liver parenchyma. The presence of granulomas did not confer any prognostic implication over and above that of the associated disease.

Aged↗
PubMed1988

Down-modulation of high-affinity receptors for erythropoietin on murine erythroblasts by interleukin 3.

Erythropoiesis is regulated by the glycoprotein hormone erythropoietin (Epo) and by several other factors including interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor. The possibility that IL-3 and GM-CSF may act by modulating Epo receptor expression was investigated using erythroblasts purified from the spleens of phenylhydrazine-treated mice. AT 37 degrees C, in the presence of sodium azide to inhibit receptor internalization. 125I-labeled human recombinant Epo bound to a single class of high-affinity receptors on splenic erythroblasts (450 sites/cell, Kd = 700 pM). Autoradiographic studies indicated that 94% of specifically bound Epo was associated with erythroblasts, decreased Epo binding being observed with increasing erythroid cell maturation. Whereas recombinant mouse IL-3 and GM-CSF did not compete with 125I-Epo for binding to the Epo receptor, preincubation of cells with IL-3 resulted in a concentration-dependent loss of 125I-Epo binding without altering the affinity of residual receptors for Epo. Complete loss of Epo receptors was effected within 2 h at IL-3 concentrations above 2500 U/ml. Preincubation with recombinant mouse GM-CSF had no effect on binding, even at 100,000 U/ml. In comparison, preincubation of cells with Epo (50 U/ml) caused complete loss of 125I-Epo binding within 30-60 min, an effect not explained by receptor saturation with unlabeled Epo. Thus, in addition to trans-down-modulating growth factor receptors of the granulocyte-macrophage series, IL-3 also trans-down-modulates a growth factor receptor of the erythroid lineage.

Animals↗
PubMed1987

Transmitter localization and vesicle turnover at a serotoninergic synapse between identified leech neurons in culture.

An electron microscopic study has been made of chemical synapses that develop between identified nerve cells isolated from the CNS of the leech and maintained in culture. Structures resembling synapses were observed in pairs of Retzius cells and P sensory cells at which chemical transmission had been demonstrated by recording with microelectrodes. Vesicle recycling was shown by following the uptake of extracellular markers after stimulation. The membrane separation between the presynaptic Retzius cell (which is known to liberate serotonin) and the postsynaptic P cell was wider in synaptic than in extrasynaptic regions. The Retzius cell contained clusters of clear vesicles apposed to thickenings of the presynaptic membrane. These clear vesicle clusters were capped by a layer of dense core vesicles that did not contact the presynaptic membrane thickenings. Subsynaptic cisternae were found in the postsynaptic cell opposite the presynaptic membrane thickenings. Occasional slight postsynaptic membrane thickenings were seen. Extracellular material was observed within the synaptic cleft. Similar synaptic structures developed between pairs of Retzius cells in culture; even a single Retzius cell was able to form autapses upon itself. Structures resembling transmitter release sites were found in Retzius cells at a distance from any postsynaptic membranes. These are presumed to be locations for the diffuse release of transmitter. Presynaptic structures resembling release sites were never observed in P cells apposed to Retzius cells. Antibody to serotonin (5-HT) labelled with colloidal gold showed serotonin to be localized in the dense core vesicles in Retzius cells. Stimulation of pairs of Retzius and P cells by raised concentrations of K+ resulted in uptake of extracellular markers. Only Retzius cells became labelled. Ferritin was found in cisternae, in dense core vesicles, and in clear vesicles. HRP was found in cisternae and in clear vesicles. Colloidal gold was taken up by coated vesicles and was occasionally found in both clear and dense core vesicles. The uptake of extracellular markers following stimulation was blocked by high Mg++. These results show that structures develop between pairs of cells at which chemical transmission develops and that transmitter release leads to turnover of dense core and clear vesicles.

Animals↗
PubMed1987

Late effects of total body irradiation.

Late effects of chemo-radiotherapy conditioning before bone marrow transplantation (BMT) are being increasingly recognised in long-term survivors, particularly children. They can be divided into two categories: those affecting hormonal status and those affecting specific organ function. All women treated develop ovarian failure with low levels of beta-oestradiol and raised values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In males, raised FSH and LH values are found with normal testosterone levels but most patients have azoospermia. In children, puberty is usually but not invariably delayed by treatment but can be induced by appropriate hormone replacement. Compensated hypothyroidism was found in 6/30 children. Growth hormone secretion may be impaired especially if previous cranial irradiation has been given. In children, a reduction in sitting height has been observed. Cataract has occurred in 20% of children between 3 and 6 years after treatment. Two second tumours have been observed. No other major organ toxicities have been encountered.

Adult↗
PubMed1984

Restorative proctocolectomy with a three-loop ileal reservoir for ulcerative colitis and familial adenomatous polyposis. Clinical results in 66 patients followed for up to 6 years.

The results of restorative proctocolectomy with a three-loop ileal reservoir were reviewed. Of 66 patients treated between 1976 and 1982, 52 had ulcerative colitis and 14 had familial adenomatous polyposis. The temporary ileostomy was closed between 2 and 78 months previously in 63 cases. Of these, three patients had had the reservoir removed and two were lost to follow-up. One other patient was subsequently found to have Crohn's disease. Function was assessed in 55 patients who had undergone closure of the ileostomy more than 8 weeks previously. Mean frequency of defecation was 3.7 per 24 hours (range 1-9.5) and 11 patients (20%) were taking antidiarrheal medication. Spontaneous defecation occurred in 22 patients (40%) while 29 (52.7%) had to use a catheter passed per anum. Four patients defecated spontaneously but sometimes used a catheter. Continence was normal in 36 (65.4%) and minor leakage once every 2 to 3 days occurred at night in 16 (29.1%). Three patients (5.4%) had some soiling during day and night. Troublesome perianal soreness (five patients, 9.1%) necessitated a defunctioning ileostomy in one. Fifty-four of the 55 patients assessed preferred their quality of life to that with an ileostomy.

Adult↗
PubMed1984

Development of markers for cholinergic neurones in re-aggregate cultures of foetal rat whole brain in serum-containing and serum-free media: effects of triiodothyronine (T3).

Development has been studied in re-aggregate cultures derived from the 16 day foetal rat brain and the effects of triiodothyronine (T3) investigated. Cultures were maintained in either a medium containing 10% serum (S+), or in serum-free culture medium (S-) or in serum-free medium containing 30nM T3. The muscarinic cholinoceptor, measured by specific binding of [3H]-quinuclidinyl benzitate ([3H]-QNB) at 9 and 14 days in vitro, was at a lower level in the serum-free cultured cells compared with those in serum-containing culture medium (S+). In cultures in the latter medium, receptor concentration at day 14 was of a similar magnitude to that in rat brain at an equivalent postnatal age. Binding increased with development from 9 to 14 days in vitro in the S+ medium but not in the S- medium. T3 treatment caused an 85% increase in [3H]-QNB binding compared with the cultures in S- medium at day 14 to a level equivalent to that found in the cells grown in S+ medium. This increase was reflected in the Bmax but not in the KD (approx. 0.1nM). Choline acetyltransferase (ChAT) activity developed more slowly in the S- medium than in the S+ medium where the specific activity approximated values obtained in vivo. T3 treatment of cultures grow in S- medium significantly enhanced the developmental rate of increase of ChAT activity. The characteristics of [3H]-choline uptake and metabolism in the cultures was examined. Uptake was strictly Na+-independent but was energy-dependent, and inhibited by 2, 4'-dinitrophenol (2, 4'-DNP) and cooling (0-4 degrees C). Neither iodoacetate nor ouabain had any effect on the amount of uptake. Hemicholinium (HC3) was a potent inhibitor of uptake (70% inhibition at 10 microM HC3). Metabolism studies showed virtually no conversion to [3H]-acetylcholine ([3H]-ACH) in reaggregates grown in either the S+, S- or T3 containing media. However, a small amount of [3H]-choline was incorporated into phosphorylcholine. T3 treatment had no effect on this metabolic profile. The kinetics of [3H]-choline uptake by the re-aggregates was also studied in the re-aggregate cultures (after 12 and 22 days in vitro) using [3H]-choline at 0.05-100 microM. Both Eadie-Hofstee transformation and least-squares analysis of the data showed that the uptake comprised only a single low-affinity component with an apparent Kt = approx. 50 microM. Unlike ChAT and [3H]-QNB binding, there appeared to be no difference between the uptake in the different culture conditions. 6 It is concluded that the differentiation of cholinergic neurones and muscarinic receptors in serum-free cultured re-aggregates from foetal rat brain is enhanced by thyroid hormone treatment. The development of [3H]-choline uptake does not seem to be associated with cholinergic cells under these culture conditions, and is unaffected by thyroid hormone treatment.

Animals↗
PubMed1983

Structural and functional analysis of synaptic transmission between identified leech neurones in culture.

The fine structure and physiological properties of chemical synapses that develop between identified leech neurones in culture have been studied by electron microscopy and by quantal analysis. Earlier work has shown that the transmitter liberated by isolated Retzius cells, serotonin, evokes chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s) in P sensory cells, and also in Retzius cells. When pairs of Retzius cells or Retzius and P sensory cells were placed in close apposition in culture for a few days, their somata extended numerous fine processes which came into contact and interdigitated. In the region of interdigitation, only narrow spaces, approximately 20-25 nm wide separated the membranes. The appearance of the cytoplasm of the two neurones was distinctive: in particular, Retzius cells contained agranular vesicles, as well as abundant dense core vesicles which were not as prevalent in P cells. Structures resembling synapses developed by 4 days, with characteristic vesicles clustered in terminals of the Retzius cell apposed to the post-synaptic membrane. In the presence of raised Mg or lowered Ca in the culture medium, the i.p.s.p. in the P cell evoked by an impulse in the Retzius cell became diminished in amplitude. The time-to-peak and half-time of decay were unchanged. Under these conditions, with repeated stimulation, quantal fluctuations of these post-synaptic potentials and failures were observed. In addition, there occurred spontaneous events which resembled miniature synaptic potentials and had amplitudes and time courses similar to those of the unitary events evoked by presynaptic impulses. The amplitudes of evoked synaptic potentials in raised Mg were distributed in accord with the Poisson equation. The agreement was good when either the spontaneous miniature potentials or the failures of evoked release were used to calculate m, the mean number of quanta per trial. With larger values of m the results were distributed as predicted by the binomial equation. These morphological and electrophysiological experiments together indicate that the inhibitory potentials observed in P cells result from quantal units of transmitter released by presynaptic terminals of the Retzius cell which are in close apposition to the post-synaptic membrane.

Action Potentials↗
PubMed1981

Disseminated infection with mycobacterium chelonei in a haemodialysis patient.

M. chelonei ssp. chelonei was isolated over a period of 5 months from abscesses on various sites of hands and feet of a patient on maintenance dialysis. The organism was resistant in vitro to a greater number of antimicrobials and treatment in turn with gentamicin, vancomycin, erythromycin, doxycycline and co-trimoxazole had to be supplemented by surgical drainage of abscesses. Examination of the dialysis circuit revealed repeatedly the presence of M. chelonei and M. fortuitum in the water softener resin and other sites. The significance of this finding is discussed.

Abscess↗
PubMed1980

The 4-methylumbelliferone sulphate sulphatases of human tears.

The properties of human tear 4-methylumbelliferone sulphate sulphatase (EC 3.1.6.1) have been investigated. More than 80% of the enzyme activity behaved as the acidic A isoenzyme on isoelectric focusing and DEAE-cellulose ion exchange chromatography. The distribution of enzyme activity in a normal population has been investigated. The least interindividual variation was seen when enzyme activities were calculated as units per mg tears. The alpha-galactosidase, beta-N-acetylglucosaminidase and sulphatase enzyme activities in human tears varied independently of each other. The use of tear sulphatases for the detection of metachromatic leukodystrophy (McKusick 24980) is discussed.

Acetylglucosaminidase↗