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Biomedical subjects

K Evans

Publications and source records attributed to K Evans.

At least 145 records · Page 8Linked to original sources
PubMed1985

Isolation of a clone coding for the alpha-subunit of a mouse acetylcholine receptor.

The mouse cell line BC3H-I synthesizes an acetylcholine receptor (AChR) with the pharmacological properties of a muscle nicotinic cholinergic receptor. We have purified mRNA from this cell line and used the size-fractionated poly(A)+RNA to produce a cDNA library of approximately 50,000 clones. The library was screened with a subclone containing genomic sequences coding for the putative acetylcholine-binding site of the alpha-subunit of chicken AChR. We obtained a plasmid, pMAR alpha 15, with a 1,717-base pair insert. The insert cDNA has 26 nucleotides at the 5'-end which code for a portion of the signal peptide followed by a single open reading frame of 1,311 nucleotides which code for a protein of 49,896 daltons. The insert has 377 bases of 3'-untranslated sequence with 3 polyadenylation sites. Radiolabeled plasmid DNA has been used to identify homologous RNA species of about 2 kilobases in Northern blot analyses of poly(A)+ selected RNA from BC3H-I cells. A similar size mRNA is seen in innervated mouse diaphragm and leg muscle, and both mouse and rat brain. Comparisons of the deduced amino acid sequence of the mouse AChR alpha-subunit with Torpedo marmorata, T. californica, chicken, human, and calf sequences show overall homologies of 80%, 80%, 86%, 96%, and 95%, respectively. More detailed analyses reveal a non-random distribution of amino acid substitutions in several structural domains. Based on the absolute conservation of cysteine residues, a new model for the arrangement of the disulfide bonds in the extracellular portion of the alpha-subunit is proposed.

Amino Acid Sequence↗
PubMed1984

Autoreactive rat T-cell lines: establishment and cellular characteristics.

Stable self-reactive T-cell lines were established from the draining lymph nodes of Buffalo rats primed with rat thyroglobulin (Tg) in complete Freund's adjuvant. Following two rounds of in vitro selection with Tg or with purified protein derivative (PPD) of Mycobacterium tuberculosis, Tg- or PPD-specific lines were selected. Self-reactivity, manifested by a potent proliferative response of these lines to syngeneic stimulators in the absence of the selecting antigen (Tg or PPD), emerged by 3-4 weeks after the establishment of the lines. This proliferation could not be attributed to reactivity against heterologous serum components. Despite this syngeneic mixed-leukocyte reaction (SMLR) which was readily detectable, specific stimulation by Tg or PPD over the level of the SMLR could still be demonstrated. These lines also responded to concanavalin A but not to allogeneic stimulator cells. More than 95% of T cells of these lines displayed the rat T-helper-cell-specific (W3/25) marker and they secreted a defined lymphokine, T-cell growth factor (TCGF), upon stimulation with syngeneic stimulator cells, independent of the presence of soluble antigen. T-Cell lines such as the ones described here will be useful in elucidating the biological significance of the AMLR/SMLR and its relation to nominal antigen reactivity.

Animals↗
PubMed1983

Carbohydrate malabsorption in infants with diarrhea studied with the breath hydrogen test.

Fermentation of malabsorbed carbohydrate (CHO) reaching the colon was studied by measuring peak breath hydrogen (H2) production between feedings in 28 H2-producing hospitalized infants with diarrhea. Patients who required fewer than six days of hospitalization had lower breath H2 values when tested soon after admission than those who required longer stays. Patients hospitalized for more than five days had lower H2 amounts at discharge than on admission. Peak breath H2 values decreased when glucose was substituted for glucose polymers in formulas, or when the formula was fed by continuous drip via a nasogastric tube instead of by orally administered bolus. Glucose-positive and acidic stools were encountered occasionally and were associated with decreased H2 levels. The responses of H2 levels, stool pH, and glucose excretion after changes in patient management or intestinal metabolism of CHO reflect alterations in the balance between proximal intestinal absorption and distal colonic fermentation. Malabsorbed CHO that reaches a competent colon is utilized via microbial conversion, as indicated by high H2 levels, in the absence of glucose-positive and acidic stools. The presence of glucose in the feces or acidic stools indicates an inability of the colon to completely metabolize and absorb CHO or its products of fermentation.

Breath Tests↗
PubMed1982

Regional (14C) 2-deoxyglucose uptake during vibrissae movements evoked by rat motor cortex stimulation.

Repetitive left mystacial vibrissae movements were produced by electrical stimulation of right motor cortex (MI) were a bipolar electrode in the alert, unanesthetized rat. Regional increases of (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically during these left vibrissae movements. Uptake of 2DG increased in a 2-4-mm-diameter area about the stimulating electrode in right MI and in a smaller region in left MI cortex. Columnar increases of 2DG uptake occurred bilaterally in somatosensory cortex in the face region of somatosensory cortex (SI). Bilateral increases of 2DG uptake occurred subcortically in dorsolateral caudate-putamen (CP) and subthalamic nucleus. Primary right-sided increases of 2DG uptake occurred in other basal ganglia structures including dorsal globus pallidus (GP), posterior, entopeduncular nucleus (EPN), ventrolateral substantia nigra pars reticulata (SNr), and anterolateral substantia nigra pars compacta (SNc). Uptake of 2DG increased on the right side of the following thalamic regions: much of the ventrolateral (VL) nucleus, particularly dorsally; the anterodorsal reticular nucleus; dorsolateral posteromedial (POm) nucleus; the ventromedial nucleus; and dorsolateral parafasicular nucleus. The anterior and ventral posterior portions of VL were not activated. Caudal to thalamus right-sided 2DG uptake increased in the medial, ventral, and lateral pontine nuclei, deep layers of superior colliculus, lateral deep mesencephalic nucleus (DMN), and nucleus cuneiformis (NCU). UPtake of 2DG increased in right rostral parvocellular and red nucleus in a few animals. Discrete portions of the right internal capsule and right medial pyramidal tract increased 2DG uptake during MI stimulation. Uptake of 2DG increased on the left side of the brain during right MI stimulation in the left lateral nucleus (NL) of cerebellum and in several discrete regions of left cerebellar hemisphere granule cells including anterior paravermis, lobulus simplex, crus II, and the paramedian lobule. Uptake of 2DG increased in left nucleus of the spinal tract of the trigeminal nerve (ntV) ventrally in subnuclei interpolaris and oralis. Left lateral portions of the facial nucleus were activated in a few animals. The lateral portions of the facial nucleus are known to project to vibrissae musculature. All of the above structures may be involved in the motor-sensory processing responsible for vibrissae movements. Regions not previously suggested to play a major role in vibrissae movements include DMN and NCU. Though NCU has been called the "locomotor center" it may play a role in facial movements as well. Polysynaptic activation of GP, EPN, NL, and cerebellar hemisphere occurred since no connections between MI and these regions exist. A pathway from ntV to POm to MI and SI is suggested to provide proprioceptive input to motor-sensory cortex from the moving vibrissae since neither the principal trigeminal sensory nucleus nor the ventrobasal nucleus of the thalamus increased 2DG uptake during MI stimulation.

Animals↗
PubMed1982

Thiamine deficiency limits glucose utilization and glial proliferation in brain lesions of symptomatic rats.

The effects of thiamine (B1) deficiency on local CMRglu (LMCRglu) in the vestibular nuclei were studied with the 14C-2-deoxyglucose autoradiographic method in awake asymptomatic and symptomatic rats. Animals on the B1-deficient diet for 98 days developed symptoms of ataxia and opisthotonos. The results show that B1 deficiency produces: (1) bilateral vestibular nuclei lesions in symptomatic animals; (2) very low LCMRglu rates in these lesions; and (3) limitation of glial proliferation in the lesions. Giving B1 to B1-deficient symptomatic animals produced a cellular proliferation response consisting mostly of microglia in the lesioned areas of the vestibular nuclei and a high LCMRglu rate in the regions of microglial proliferation.

Animals↗
PubMed1982

Survivors of neuroblastoma and ganglioneuroma and their families.

The main purpose of this study was to see if the offspring of surviving neuroblastoma, ganglioneuroblastoma, or ganglioneuroma patients have themselves a risk for developing tumours. No such risk was found. There was a total of 45 liveborn children who were all healthy. These children have passed through about 37 lifetimes of risk for developing neuroblastoma and about six lifetimes of risk for developing ganglioneuroma. No excess of cancers was found among parents and sibs. It was interesting that there was a large female excess (35:12) among these survivors. One factor which may give rise to a better prognosis in females is the tendency of their tumours to mature to benign forms.

Adult↗
PubMed1982

A three generation family study of cleft lip with or without cleft palate.

A family study of cleft lip, with or without cleft palate, was based on those treated by operation at The Hospital for Sick Children, London, between 1920 and 1939 in order to give information on the proportion affected of children and grandchildren. The probands were those who had survived, were successfully traced, and found to have had at least one child. Care was taken to exclude patients who were traced through a child, whether normal or affected, and not through the usual tracing procedure. Patients with recognised syndromes were also excluded. Because the series was based on patients who had survived and reproduced it was biased in favour of those with milder degrees of the malformation, and against those with any severe associated malformation. The proportion affected of children of probands was 3.15% (+/- 0.56), of sibs 2.79% (+/- 0.52), and of parents 1.18% (+/- 0.37), respectively. The lower proportion of parents affected is attributed to reduced reproductive fitness of patients born two generations ago. The proportion affected of nephews and nieces, aunts and uncles, and grandchildren was 0.47% (+/- 0.18), 0.59% (+/- 0.13), and 0.8% (+/- 0.6) respectively. The proportion affected of first cousins was 0.27% (+/- 0.08). The birth frequency of cleft lip (+/- cleft palate) is estimated to be about 0.1% in England. There were two first cousin and one second cousin marriages among the marriages of the parents. There was no increase of cleft palate among the relatives of the probands. The proportion of sibs affected increased with increasing severity of the malformation in the proband, where the proband was female, and where the proband had an affected parent or already had one affected sib. It was not, however, increased where a more remote relative was affected. The proportion of children affected was not increased when the proband had an affected parent or sib, but few families provided information. The most economical hypothesis to explain the findings is the multifactorial threshold model. The birth frequency of the malformation and the family patterns found make it improbable that one single mutant gene makes a major contribution to the liability to develop the condition.

Adult↗
PubMed1982

A family study of isolated cleft palate.

A family study was based on 245 boy and 329 girl patients treated surgically for non-syndromic cleft palate between 1920 and 1929; 86 and 81 respectively were traced and had had children. These 167 were the probands for the family study and were interviewed in their homes. None was born to a consanguineous marriage. Altogether they had had 384 children of whom 11 had cleft palate (2.9 +/- 0.9%). They had 398 sibs of whom five had cleft palate, 117 grandchildren of whom one was affected, and 517 nephews and nieces of whom one was affected. This is the largest series yet available on which to base an estimate of the risks to children of patients with non-syndromic cleft palate. The risk is probably increased where a parent or sib of the proband is affected and increased to a lesser degree where a second or third degree relative is affected. The family patterns in these and other studies suggest that the aetiology of cleft palate is heterogeneous, with some families showing modified dominant inheritance. This is in contrast to cleft lip (+/- cleft palate) where the data are consistent with a multifactorial threshold model.

Adult↗
PubMed1982

Local cerebral glucose utilization in the symptomatic thiamine-deficient rat: increases in fornix and pyramidal tract.

Local cerebral glucose utilization (LCGU) was measured in asymptomatic rats on a thiamine (B1)-deficient diet for 70 days and in symptomatic rats on a B1-deficient diet for 98 days. LCGU increased in postcommissural fornix (F), pyramidal tracts (P), and inferior internal capsule (CAI) of symptomatic, compared with asymptomatic B1-deficient rats but decreased in thalamic nuclei, auditory structures, and lesioned vestibular nuclei. B1 administration to symptomatic rats improved symptoms; decreased LCGU in F. P, and CAI; increased LCGU in the lesioned vestibular nuclei; but decreased LCGU in mammillary nuclei, anteroventral nucleus of thalamus, and medial raphe. The results indicate that B1 deficiency symptoms correlate with LCGU changes in F and P and vestibular nuclei.

Animals↗
PubMed1981

Per rectal ultrasound in the investigation of prostatic disease.

Primary prostatic disease is usually assessed by digital palpation of the prostate. This method lacks objectivity and has been shown to be inaccurate, especially in the staging of primary prostatic cancer. This paper describes the investigation of 200 subjects using per rectal ultrasound. Of 70 patients with histological evidence of carcinoma of the prostate, 96% were correctly diagnosed ultrasonically and 87% correctly diagnosed by digital palpation. Of the 37 patients with ultrasonic evidence of a capsular breach, only 65% were diagnosed as such by digital palpation. A study of 10 cadaver specimens confirmed the accuracy of per rectal ultrasound as a technique for staging primary prostatic cancer . The ultrasonic appearances of the prostate, seminal vesicles and bladder base are described. Per rectal ultrasound is acceptable to patients, and its use is recommended in all cases where accurate assessment of primary prostatic cancer is required.

Adult↗
PubMed1981

A comparison between digital examination and per-rectal ultrasound in the evaluation of the prostate.

Three hundred and fifty-two patients have been examined by per-rectal ultrasound and histological confirmation of the diagnosis was obtained in 242 cases. Per-rectal ultrasound compared favourably with digital palpation both as a method of diagnosing prostatic cancer and also as a method of staging a primary tumour. Confirmation of the accuracy of this technique as a method of staging was gained by a study involving the use of cadaver material. Repeat examinations on patients with prostatic carcinoma have shown that per-rectal ultrasound is an ideal method for monitoring response of the primary tumor to treatment.

Humans↗
PubMed1981

Children of those treated surgically for Hirschsprung's disease.

The risk of recurrence of Hirschsprung's disease in sibs is reasonably well established. Survivors of early successful operations (rectosigmoidectomy) are now reaching adult life and are asking about risks to their children. The authors report a preliminary study on which to base a risk estimate. Studies on sibs show that for short segment index patients the risk to brothers is about 1 in 20 and for sisters about 1 in 100. For long segment patients the risk is about 1 in 10 irrespective of sex. In the present study it was found that one son in 52 was possibly affected, and one daughter in 47 was certainly affected, of short segment index patients. Of long segment index patients one son in three was probably affected, and the one daughter was certainly affected. One long segment patient had a child with a short segment affected and one short segment patient had a child with a long segment affected. This confirms the impression, given by single case reports of parent and child affected, that there is less likelihood of concordance in length of aganglionic segment in parent and child than in sibs. For the present it is appropriate to give an estimated risk of about 2% for offspring of short segment index patients, but a relatively higher risk for offspring of long segment index patients.

Female↗
PubMed1981

Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits.

We made simultaneous recordings from 48 bipolar electrodes to obtain epicardial isochronal maps during induced ventricular arrhythmias in dogs 3-5 days after ligation of the left anterior descending artery. There was strong evidence of a reentrant circuit (RC) that was discernible largely on the epicardial surface in 21% of ectopic beats that were analyzed. Epicardial recordings were of limited value in analyzing the arrhythmia in other beats. The reentrant circuit consisted of an arc of conduction block around which the activation front advanced in a circular fashion at slow but uneven speeds while the rest of the ventricle was activated by radial spread. The arc of conduction block around which the RC was formed was usually functional in nature, since the same area of myocardium was excitable at relatively long cardiac cycle lengths. Both the length of the arc of conduction block which defines the length of the reentrant circuit and the degree of conduction delay were crucial factors for the occurrence of reentry. A premature beat that initiated reentry resulted in a longer arc of conduction block and slower conduction compared to one that failed to induce reentry.

Animals↗
PubMed1981

An X-linked disease of the nervous system with disordered copper metabolism and features differing from Menkes disease.

We studied 2 of 4 affected boys with a new disease associated with abnormalities of copper metabolism. The four cases occurred in two generations of a family. This syndrome was similar to Menkes disease in some respects: X-linked recessive inheritance, marked psychomotor retardation with seizures, low serum copper and ceruloplasmin levels, and a block in gut copper absorption. There were also striking differences from Menkes disease. Patients had normal birthweight at term, no hypothermia, and survived beyond the usual Menkes age group with static neurologic disease including hypotonia and choreoathetosis. In addition, general examination of both children was unremarkable apart from undescended testes and growth retardation. The hair, facies, and skin were normal and there was no radiologic evidence of bony changes. Detailed studies of copper absorption were performed.

Brain Diseases, Metabolic↗