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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 469 records · Page 26Linked to original sources

Ingestion in fetal sheep and its relation to sleep states and breathing movements.

Swallowing was recorded electromyographically in unanaesthetized fetal sheep in utero during the last third of gestation. In control fetuses bouts of swallowing were, on average, 2.0 min in duration and occurred at intervals of 2.31 h. Swallowing bouts were associated with a low-voltage electrocorticogram, eye movements and, in 82% of instances, with phasic activity in the dorsal neck muscles. These data indicate that fetuses are not in quiet (non-rapid eye movement; n.r.e.m.) sleep when swallowing and also suggest that they are not in r.e.m. sleep as conventionally defined; we consider that fetuses may be in a state of heightened activity resembling wakefulness. Swallowing bouts were always accompanied by fetal breathing movements. When a swallow coincided with an inspiratory effort the diaphragm was briefly inhibited. Evidence was obtained that bouts of fetal ingestive activity were not dependent upon outpourings of fluid from the lungs and were not significantly influenced by volume information from the gastric compartments.

Animals↗

A calcified adenocarcinoma of the lung with very high CT numbers.

A case is reported of a man with a solitary pulmonary nodule that had an average CT number of 366 HU. Biopsy of the lesion demonstrated a primary adenocarcinoma of the lung with diffuse calcification. It is concluded that high CT numbers of solitary nodules do not ensure a benign lesion.

Adenocarcinoma↗

Breathing pattern of kittens during hypoxia.

In 19 pentobarbital sodium-anesthetized kittens aged 5-34 days, inspired O2 was reduced from 21 to 6-12%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.

Abdominal Muscles↗

The uptake by man of cadmium ingested in crab meat.

Seven male volunteers with normal iron stores ate the brown meat from crabs whose diet had contained radioactive cadmium-115m. Systemic uptake of cadmium by the volunteers, derived from measurements of their residual body radioactivity several weeks after intake, averaged 2.7 +/- 0.9 (se)%, essentially as found by others in studies with extrinsically labelled food.

Adult↗

Effect of embryonic treatment with oestradiol benzoate on reproductive morphology, ovulation and oviposition and plasma LH concentrations in female quail (Coturnix coturnix japonica).

Quail eggs were injected on Day 10 of incubation with 0, 5, 10, 20 or 40 micrograms oestradiol benzoate. Females hatching from these eggs were reared on a 16L: 8D photoperiod and egg laying was recorded. Blood samples were taken at 37, 40, 43, 46, 49, 52, 55, 58 or 61 days of age and LH concentrations were measured by a double-antibody radioimmunoassay. Birds were killed at 61 days of age; ovaries and oviducts were weighed and examined. Egg laying was greatly reduced by oestradiol benzoate treatment, but for birds that did lay, age at first oviposition was normal. LH levels were not affected by oestradiol benzoate treatment, and were highest at 40 and 49 days of age. Oestradiol benzoate had no effect on ovarian weight, number of follicles with diameter greater than 1 cm, or number of post-ovulatory follicles. Oestradiol benzoate had a dose-related effect on the likelihood that females would have two oviducts, and for those females that had retained the right oviduct, the left oviduct was smaller than normal. Oestradiol benzoate-treated females were more likely to have ovulated yolks in the body cavity. Embryonic treatment with oestradiol benzoate therefore appears to inhibit egg laying by causing oviduct abnormalities, rather than by (as happens in mammals) inhibiting ovulation.

Animals↗

The pharmacokinetics in man of SK&F 93319--a new antagonist of histamine H1 and H2 receptors.

SK&F 93319, a potent histamine H1- and H2-receptor antagonist, is rapidly absorbed with a low rate of plasma clearance primarily by metabolism. Excretion is divided evenly between urine and faeces (probable biliary elimination) with little unchanged drug in the urine. Serum protein binding at low concentrations is very extensive and appears to restrict distribution of SK&F 93319. At higher concentrations (higher dose levels) reduced protein binding results in a marked proportional increase in available free drug with a consequent increase in distribution and clearance. Bioavailability is reduced at higher dose levels. The importance of factors contributing to non-linear pharmacokinetics and the potential clinical consequences are demonstrated.

Adult↗

Effect of cytotoxic chemotherapy on hepatitis B viral markers in patients with hepatocellular carcinoma.

The titre of HBsAg in the serum of patients with HBsAg seropositive hepatocellular carcinoma rose in 12 (80%) of 15 cases during chemotherapy with either adriamycin or etoposide and in five cases there was at least a four-fold rise in titre. Anti-HBs and anti-HBc status did not change and serum markers of HBV infection did not become apparent in the 32 patients who were seronegative at presentation. The chemotherapy-related rise in HBsAg titre did not appear to be responsible for deterioration in hepatocellular function and it was not associated with any change in HBeAg/anti-HBe status.

Adolescent↗

Bromoacetyl-L-carnitine: biochemical and antitrypanosomal actions against Trypanosoma brucei brucei.

One of the causative agents of the African Trypanosamiases, Trypanosoma brucei brucei is able to use high intracellular carnitine concentrations and a high carnitine acetyl transferase (CAT) activity to stimulate ATP production. This paper reports that a carnitine analogue, bromoacetyl-L-carnitine, is an irreversible inhibitor of CAT from T.brucei, non-competitively inhibits carnitine uptake by T.brucei and has a potent in vitro effect against T.brucei motility and infectivity. An in vivo action in T.brucei infected mice is also reported. These results represent a new area of investigation in the important search for new antitrypanosomal agents.

Acetylcarnitine↗

Fetal distress and the condition of newborn infants.

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth.

Acidosis↗

Structural analysis of the C-terminal region of chicken gizzard desmin.

The C-terminal sequence of chicken gizzard desmin has been examined by computer programs based on Chou-Fasman prediction of secondary structure, auto-correlation and Fourier analysis of hydrophobic residue distribution, and cross-correlation analysis of acidic and basic residues. These analyses indicate that, although parts of the desmin sequence are alpha-helical, the helical regions may not be as extensive as predicted previously. Detailed analysis of the distribution of the charged residues in the desmin sequence strongly suggests that it cannot form a tropomyosin-like coiled-coil double-helix because of the almost complete absence of stabilizing salt-bridge interactions between proximal pairs of acidic and basic residues. Although the desmin sequence does contain the tropomyosin-like hydrophobic residue distribution, differences exist in the overall distributions of hydrophobes, with clusters of these residues being found in certain regions of the desmin sequence. Analyses of the sequences of porcine desmin and vimentin reveal very similar structural characteristics for these molecules, although vimentin is predicted to have a different structure at its C-terminus.

Amino Acid Sequence↗

Intracellular pH and free calcium changes in single cells using quene 1 and quin 2 probes and fluorescence microscopy.

Photometric fluorescence microscopy has been used to measure intracellular pH (pHi) and free calcium concentrations [( Ca]i) in individual mouse thymocytes and 2H3 rat basophil leukaemic cells containing indicators for pH (quene 1) or calcium (quin 2). The pHi and [Ca]i measurements in individual 2H3 cells and mouse thymocytes and their responses to various stimuli were consistent with the corresponding data obtained from suspensions of these cells measured in a spectrofluorimeter. Photometric fluorescence microscopy of these indicators in individual cells provides a sensitive and fast method of following pHi and [Ca]i responses in individual cells.

Aminoquinolines↗

Carbocyanine dyes used as fluorescent triplet probes for measuring slow rotational diffusion of lipids in membranes.

A method for measuring the slow rotational diffusion of lipids or lipid domains in membranes has been developed. It covers the time range from 20 microseconds-5 ms, and has a greater than 5 x 10(4) molecules of probe. The method uses acyl-substituted carbocyanine dyes as fluorescent triplet probes and a laser-microscope combination for excitation and measurement of the triplet state. Rotation rates in dimyristoylphosphatidylcholine vesicles were sensitive to the liquid-to-gel transition. Slow rotations with relaxation times of about 100 microseconds were detected at the transition temperature region.

Carbocyanines↗

Diffusion characteristics of beta-aminopropionitrile in peripheral nerve.

beta-Aminopropionitrile (beta-APN), a lathyrogen, alters the physical characteristics of fibrous scar tissue and as such may have potential clinical use in treatment of injured spinal cord and peripheral nerve by reducing the physical barrier to axon regeneration. For beta-APN to exert its lathyrogenic effect, it must permeate the injury site and gain access to the developing collagenous scar. To investigate the diffusion characteristics, beta-[14C]APN solution was applied as an immersion bath to rat sciatic nerve using both in vivo and in vitro preparations for intervals of 15 to 90 min. The four experimental groups studied were (a) intact nerve, (b) hemisected nerve, (c) nerve with epineurium removed, and (d) nerve with both epineurium and perineurium removed. The isotope labeling index determined by autoradiography and scintillation counting indicated the perineurium as the primary barrier to significant diffusion of beta-APN in normal nerve. When perineurium was incised or removed, beta-APN entered the endoneurial matrix. beta-APN concentration in the epineurium and perineurium increased with increasing bathing time in vitro; but it decreased markedly after 15 min of in vivo bathing. These findings indicate that topical application of beta-APN to injured peripheral nerve would be a successful method of exposing fibrogenic intraneural tissue to the inhibitory effect on lysyl oxidase enzymes. Continuous application, however, will be necessary because of the rapid beta-APN removal documented in the vivo preparation.

Aminopropionitrile↗

Interactions of beta-adrenoceptor agonists and antagonists with the 5-hydroxytryptamine2 (5-HT2) receptor.

The effect of beta-adrenoceptor agonists and antagonists on the binding of [3H]-spiperone in the frontal cortex of the rat has been examined to determine their possible interaction with the 5-hydroxytryptamine2 (5-HT2) receptor. Methysergide and the putative 5-HT2 antagonist, pirenperone, had IC50 values in the low nanomolar range whilst 5-HT and quipazine had micromolar IC50 values. Non-selective beta-adrenoceptor antagonists ((-)-propranolol, (-)-alprenolol) had similar IC50 values to 5-HT whilst selective (beta 1- or beta 2-)antagonists, (+)-propranolol and the beta-adrenoceptor agonists, clenbuterol and dobutamine, had values at least ten-fold higher. It is suggested that inhibition of 5-HT-mediated behaviour by non-selective beta-adrenoceptor antagonists results from their action at 5-HT2 receptors while clenbuterol does not enhance 5-HT-mediated behaviours by acting at this site.

Adrenergic beta-Agonists↗

Sister chromatid exchange: variation by age, sex, smoking, and breast cancer status.

Variation in sister chromatid exchange (SCE) frequency in lymphocytes of 125 persons was compared using a multivariate general linear model. The study was performed to determine whether SCE frequency differs with respect to age, sex, smoking, and breast cancer status. Study subjects were divided into: members of two branches of families having an excess of cancer (primarily breast) including a brother and sister in one family who developed nonbreast malignancies within 1 yr of the study; women in both families successfully treated for breast cancer (all at least 5 yr posttreatment); and women from the general population with confirmed breast cancer. Controls consisted of spouses who married into the high-risk kindreds, hospital personnel, and others (primarily tradesmen without history of occupational exposure). Results show that: (1) Women with active breast cancer have a significantly higher mean SCE frequency than control women or women greater than 5 yr posttreatment for breast cancer; (2) Cigarette smokers show a significantly higher number of SCEs than was observed in nonsmokers; (3) The increase in SCE level in smokers is dose-related to exposure as measured by cumulative pack-years; (4) SCE values in both high-risk families are not significantly different from controls; (5) Neither the age nor sex of the individual affects SCE frequency; and (6) The observed distribution of exchanges agrees with that expected based on the proportion of the genome represented by each chromosome group.

Adult↗

Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex.

The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatments enhanced the carbidopa/5-hydroxytryptophan (5-HTP)-induced head-twitch response at all doses of 5-HTP examined, producing a parallel shift in the dose-response curve. A single ECS administration or single dose of desmethylimipramine had no effect. Only repeated ECS enhanced the locomotor response to injection of apomorphine. The dose-response curve shift was not parallel. A single ECS had no effect. A 6-hydroxydopamine lesion of brain dopamine terminals also enhanced the apomorphine response, but again did not produce a parallel shift in the dose-response curve. Both repeated ECS and repeated desmethylimipramine administration to rats increased the number of 5-HT2 receptor sites in rat brain. Clenbuterol had no effect. The enhancing effects of repeated ECS and clenbuterol administration on the 5-HTP-induced head-twitch response were additive. Enhanced 5-HT-mediated behavioural responses are seen in both mice and rats after these treatments. If it is assumed, therefore, that similar receptor changes occur in both species it appears that there is no relationship in either behavioural system between the ability of the treatment to alter receptor number and the change in the dose-response curve (parallel or non-parallel). All three antidepressant treatments (ECS, a tricyclic and a beta-adrenoceptor agonist) increase 5-HT-mediated behavioural responses although clenbuterol did not increase 5-HT2 receptor number. Only ECS increased dopamine-mediated responses.

5-Hydroxytryptophan↗