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Biomedical subjects

C L Smith

Publications and source records attributed to C L Smith.

At least 289 records · Page 16Linked to original sources
PubMed1987

Megabase-scale mapping of the HLA gene complex by pulsed field gel electrophoresis.

In the study of the genetic structure of mammalian chromosomes, there exists a "resolution gap" between molecular cloning experiments and meiotic linkage analyses. This gap has discouraged attempts to construct full-scale genetic maps of mammalian chromosomes. The organization of the human major histocompatibility complex was examined within this range by pulsed field gel electrophoresis. The data obtained indicate that the complex spans over 3000 kilobases and enable the construction of a megabase-scale molecular map. These results indicate that the techniques employed in DNA extraction, enzymatic digestion, electrophoresis, and hybridization are suitable for the efficient analysis of megabase regions of mammalian chromosomes and effectively bridge the resolution gap between molecular cloning and classical genetics.

Animals↗
PubMed1987

Structure, expression, and molecular mapping of a divergent member of the class I HLA gene family.

A class I gene distinct from HLA-A, -B, or -C was identified in a cosmid clone and transfected into mouse L cells. The gene, placed adjacent to the polyoma enhancer, produced a full-length class I mRNA and high levels of a 43-kDa protein in the cytoplasm. The surface expression of the gene product required its association with human beta 2-microglobulin. The protein was recognized by a xenoantiserum raised against a mixture of human B- and T-cell lines. The product was also serologically reactive with the HLA framework monoclonal antibodies. The complete nucleotide sequence of the gene was determined and a specific oligonucleotide probe was synthesized. This probe was used to identify a full-length mRNA transcript in a B-lymphoblastoid cell line (JY). The gene was mapped within a 190-kilobase Not I restriction fragment located in the telomeric portion of the human major histocompatibility complex. Distinct features of the gene include the structure of the promoter, the position of the translation initiation site, a frameshift mutation at the carboxyl terminus, the insertion of an Alu repeat element in the eighth exon, divergence in the derived amino acid sequence, and the lack of expression of the gene in some cells.

Amino Acid Sequence↗
PubMed1987

Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors.

We have isolated and sequenced cDNAs for corticosteroid binding globulin (CBG) prepared from human liver and lung mRNAs. Our results indicate that CBG mRNA is relatively abundant in the liver but is also present in the lung, testis, and kidney. The liver CBG cDNA contains an open reading frame for a 405-amino acid (Mr 45,149) polypeptide. This includes a predominantly hydrophobic, leader sequence of 22 residues that precedes the known NH2-terminal sequence of human CBG. We, therefore, predict that the mature protein is composed of 383 amino acids and is a polypeptide of Mr 42,646. A second, in-frame, 72-base-pair cistron of unknown significance exists between the TAA termination codon for CBG and a possible polyadenylylation signal (AATAAA) located 16 nucleotides before the polyadenylylation site. The deduced amino acid sequence of mature CBG contains two cysteine residues and consensus sequences for the attachment of six possible N-linked oligosaccharide chains. The sequences of the human lung and liver CBG cDNAs differ by only one nucleotide within the proposed leader sequence, and we attribute this to a point mutation. No sequence homology was found between CBG and other steroid binding proteins, but there is a remarkable similarity between the amino acid sequences of CBG and of alpha 1-antitrypsin, and this extends to other members of the serpin (serine protease inhibitor) superfamily.

Amino Acid Sequence↗
PubMed1987

Haemodynamic effects of the i.v. administration of cimetidine or ranitidine in the critically ill patient. A double-blind prospective study.

The cardiovascular effects of i.v. cimetidine 200 mg or ranitidine 50 mg were investigated in a double-blind cross-over study of 20 critically ill patients in an intensive therapy unit. Both agents caused transient decreases in mean arterial pressure and systemic vascular resistance, although there was no significant change in heart rate, cardiac output, central venous pressure, pulmonary artery wedge pressure or pulmonary vascular resistance in either group. The hypotensive, systemic vasodilatory effect was more common after cimetidine than after ranitidine. Also, it was significantly greater after cimetidine. Both histamine H2-receptor antagonists may cause hypotension in the critically ill patient.

Adult↗
PubMed1987

Pre-oxygenation and the parturient patient.

The effects of pre-oxygenation were studied by continuous expired oxygen analysis in twenty pregnant patients and ten nonpregnant controls. The Magill system and a demand valve breathing system were both studied with tidal and vital capacity breathing. Rapid pre-oxygenation was possible with the demand valve system but the technique was associated with air leaks around the mask. Vital capacity breathing with the Magill system was inefficient in practice because of rebreathing and air leaks, and the recently proposed four vital capacity breath technique provided suboptimal alveolar oxygenation in pregnant subjects. Oxygenation in pregnant subjects was significantly faster than in nonpregnant controls and was achieved after just 2 minutes of tidal breathing from a standard Magill system with a prefilled reservoir. Care was necessary to ensure a gas-tight seal around the facemask.

Adult↗
PubMed1987

Vecuronium infusions in patients with renal failure in an ITU.

The use of an infusion of vecuronium is described in seven patients with renal and respiratory failure in an intensive therapy unit. Neuromuscular function was monitored throughout using the train-of-four twitch technique. A bolus dose of vecuronium (0.1 mg/kg) was given, followed immediately by a continuous infusion (0.05 mg/kg/hour). The infusion rate was adjusted until the first twitch of the train was below 20% of control and then run at a constant rate. There was a marked variation in the dose of vecuronium administered (0.01-0.065 mg/kg/hour [corrected]). Two patients, who appeared to be most sensitive to the drug, were both receiving metronidazole. Recovery of neuromuscular function was extremely prolonged and widely variable (6-37 hours) on stopping the infusion. No adverse cardiovascular effects or evidence of histamine release were seen as a result of administration of the drug. Vecuronium is probably more suitable for administration in bolus doses rather than by infusion in patients with renal and respiratory failure.

Acute Kidney Injury↗
PubMed1987

Prolonged paralysis following an infusion of alcuronium in a patient with renal dysfunction.

The case is described of a patient who underwent artificial ventilation in an intensive therapy unit and received an infusion of alcuronium 10 mg/hour for more than 4 days, in the presence of significant renal (and later, some degree of hepatic) impairment. Prolonged and profound neuromuscular block persisted despite haemodialysis (5 hours on each of 3 days) followed by 72 hours of continuous haemofiltration; it appeared to resolve only after plasma exchange (4 litres). The total of persistent block, for 9 days after the infusion had been stopped, is thought to be the longest period ever reported after administration of alcuronium. Neuromuscular block was monitored throughout this period using the train-of-four twitch technique. The potentiating effects of concurrent aminoglycoside therapy and hepatic dysfunction on the degree of paralysis are discussed.

Alcuronium↗
PubMed1987

Patterns of acid reflux in complicated oesophagitis.

Oesophageal manometry and 24 hour ambulatory pH recordings from the distal oesophagus were carried out in 25 patients with complications of oesophagitis (stricture, Barrett's oesophagus or oesophageal ulcer) and compared with 25 patients with uncomplicated oesophagitis. Acid reflux was more severe in the complicated group with 26.2% of time below pH 4 compared with 11.3% in uncomplicated patients (p less than 0.01). This difference was most marked at night, when complicated patients had long periods of acid reflux with 35.6% time less than pH 4 compared with 5.2% uncomplicated (p less than 0.001). The mean duration of nocturnal acid reflux was 15.4 minutes (2.1 minutes uncomplicated, p less than 0.001). Oesophageal motility was markedly abnormal in all groups, but with no demonstrable differences in lower oesophageal sphincter pressure or peristalsis between the groups. Patients with complications of oesophagitis have different patterns of acid reflux from uncomplicated patients, with prolonged nocturnal bathing of the oesophageal mucosa, which may be the cause of stricture formation, metaplasia, or ulceration.

Adolescent↗
PubMed1987

H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response?

Ambulatory oesophageal pH, oesophageal manometry and fasting serum gastrin concentrations were carried out on 28 patients with reflux oesophagitis, before and during treatment with ranitidine 300 mg bd. Fourteen patients healed endoscopically at six weeks (group A) and 14 had residual oesophagitis (group B). Group A were characterised by a lower serum gastrin concentration before treatment (4.52 pmol/l; 2.4-10: mean and range) than group B (11.1 pmol/l; 3.5-21: p less than 0.05) and showed a marked reduction in acid reflux on treatment to near normal values. Mean per cent time below pH4 fell from 14.9 to 4.2 in group A (p less than 0.05) but was not affected in group B (14.2-15.6, not significant). Abnormal oesophageal motility was found in 13 patients from each group. This did not inhibit the response to ranitidine, and was not improved by healing of oesophagitis.

Adolescent↗
PubMed1987

Inflammatory bowel disease: the in vitro effect of sulphasalazine and other agents on prostaglandin synthesis by human rectal mucosa.

1. Prostaglandin (PG) E2 and F2 alpha synthesis in vitro by human rectal mucosa was significantly greater in patients with Inflammatory Bowel Disease (IBD) than in controls. 2. The addition of 250 microM sulphasalazine (SASP) significantly increased synthesis by rectal mucosa from patients with IBD, (ulcerative colitis and Crohn's disease) and controls after 1 h of incubation in Krebs' solution at 37 degrees C. 3. Flurbiprofen, indomethacin, sodium salicylate and 5-aminosalicylic acid decreased PGE2 and F2 alpha synthesis. 4. Sodium carbenoxolone decreased PGF2 alpha synthesis but had no effect on PGE2. Disodium cromoglycate, sulphapyridine, salicylazosulphadimidine and methylsulphasalazine had no effect on PG synthesis. 5. The data show marked variations in effect on PG synthesis in vitro of substances that have been investigated clinically for their actions on IBD.

Aged↗
PubMed1987

Peripheral specification of sensory neurons transplanted to novel locations along the neuraxis.

Thoracic dorsal root ganglia in bullfrogs contain sensory neurons that innervate the skin of the trunk and have synaptic connections in the dorsal horn of the spinal cord. The ganglion that innervates the forelimb contains, in addition to cutaneous afferents, many muscle afferents that project more ventrally in the spinal cord and make monosynaptic connections with motoneurons. In the present study, we have transplanted thoracic sensory neurons to the brachial level in tadpoles to discover whether they can innervate forelimb muscles and, if so, whether they form central connections characteristic of forelimb muscle afferents. The ganglion that normally supplies the forelimb was removed from tadpoles and replaced with 2 thoracic ganglia. After the tadpoles completed metamorphosis, the peripheral and central connections of the transplanted thoracic sensory neurons were examined with anatomical and electrophysiological techniques. When the ganglia were transplanted at stage XIV or earlier, transplanted sensory neurons innervated the forelimb and projected into the brachial spinal cord. Electrical stimulation of forelimb muscle nerves evoked impulses in the dorsal root, indicating that some centrally projecting sensory neurons were muscle afferents. Furthermore, muscle afferents were also activated by stretching muscles which suggest that they terminated on spindles. HRP labeling of the central projections revealed that transplanted sensory neurons terminated at sites characteristic of both cutaneous and muscle afferents. The pattern of synaptic connections was assessed by recording intracellularly from motoneurons. Stimulation of muscle afferents produced monosynaptic EPSPs in motoneurons. As in normal frogs, triceps muscle afferents projected more strongly to triceps motoneurons than to subscapularis and pectoralis motoneurons, while subscapularis afferents projected to all 3 types of motoneurons. Thus, the transplanted sensory neurons formed central connections appropriate to their novel peripheral targets. These observations suggest that interactions between sensory neurons and their targets may be important in determining their central connections.

Animals↗
PubMed1987

Evaluation of factors involved in calcium stone formation.

The role of urinary calcium oxalate supersaturation in the initiation of calcium stone formation is unclear since 24-hour urine collections from both stone-formers and nonstone-formers are supersaturated for calcium oxalate. Urinary supersaturation for calcium phosphate, uric acid, and monosodium urate or decreased excretion of inhibitors of stone formation, citrate and magnesium, may also contribute to calcium stone formation. To assess these possibilities we studied variations within 24 h of determinants for calcium stone formation. Six consecutive 4-hour urine specimens were collected from stone-formers (n = 15) and nonstone-formers (n = 11) during their usual diet and activities. Compared to nonstone-formers, urine from stone-formers had increased calcium concentrations, while pH and oxalate, phosphorus, uric acid, magnesium and citrate concentrations were not different. Urine from both stone-formers and nonstone-formers was always supersaturated for calcium oxalate, uric acid and monosodium urate with no difference between the groups. Urine from stone-formers was always supersaturated for calcium phosphate as brushite, while urine from nonstone-formers was mostly undersaturated for brushite. In addition to these physicochemical studies, we reviewed the composition of 235 stones containing calcium oxalate and analyzed it by crystallography. The center of 67% of these stones contained calcium phosphate. These physicochemical and stone analysis data suggest that precipitation of a calcium phosphate crystal nidus may contribute to the initiation of many calcium stones.

Adult↗
PubMed1987

An antegrade surgical uterine flush technique for ova collection in the ewe.

A surgical uterine flush technique was evaluated for percentage of ova/corpora lutea (CL) collected and development of reproductive adhesions in 79 superovulated ewes. The median collection rate for ova/CL was 70%, and 47 of 79 ewes had greater than or equal to 67% ova/CL. At 50 to 80 days after uterine flushing, celiotomies were performed on 50 of the 79 ewes to evaluate the reproductive tract for adhesions. Adhesions of the reproductive tract were not found. Thirty ewes were given prostaglandin F2 alpha, were mated, and became pregnant. The ova collection rates were comparable with rates reported in ewes in which oviductal flush methods were used; however, adhesions did not develop and reproductive function was maintained after surgery.

Animals↗