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Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

At least 199 records · Page 11Linked to original sources

Endoscopic screening for premalignant changes 25 years after gastrectomy: results of a five-year prospective study.

Sixty-three partial gastrectomy patients an average 20 years after surgery were reviewed by endoscopy and biopsy in 1977. No cases of invasive carcinoma were found. The patients were then divided into two groups. Those with moderate epithelial dysplasia (13 patients) were reviewed at 6-12 monthly intervals. One patient developed severe dysplasia but none developed an invasive carcinoma. The remaining patients with either no or mild dysplasia were offered endoscopy after 5 years and 24 agreed. Of the 12 patients with no dysplasia at the outset: 5 still had no dysplasia 5 years later, 3 had mild dysplasia and 4 now had moderate dysplasia. There were 12 with mild dysplasia at the first endoscopy, 9 remained unchanged at the review and 3 had moderate dysplasia. If dysplastic changes in gastric mucosa are pre-malignant, progression to invasive carcinoma would appear to be slow. Even 25 years after gastrectomy only a modest deterioration in the grade of dysplasia was found and no invasive cancer.

Aged↗

Age differences in water maze performance and swimming behavior in the rat.

This study was designed to determine the earliest age at which a water maze task could be used to measure learning in rats. In Experiment 1, 24 litters of Sprague-Dawley rats were used. Eight litters per group were tested beginning at 18, 28, or 38 days of age for their ability to learn a positional discrimination in a Y-shaped water maze. Results indicated that the 28 day olds were better able to learn the task than were the 18 or 38 day groups. Performance by the 38 day olds was impaired by an immobilization response. This response is known to be influenced by catecholaminergically-active drugs [18, 19, 20], and may result from ongoing maturation in these systems. The difference in learning abilities between the 18 day and 28 day groups was further investigated in Experiment 2. In this study, 24 litters of Sprague-Dawley rats were tested for acquisition of the discrimination at 18, 20, or 22 days of age. At each age, 8 litters were tested. Results showed that significant improvements in the ability to learn the Y-maze task occurred between 20 and 22 days of age. Results of both experiments suggest that this measure of learning may be employed in rats as young as 22 days of age, but should be avoided in 38 day old rats.

Age Factors↗

Vagal and gastric connections to the central nervous system determined by the transport of horseradish peroxidase.

Horseradish peroxidase (HRP, Sigma Type VI) crystals were encased in a parafilm envelope and applied to the transected central ends of the left and right cervical vagus nerves and the anterior and posterior esophageal vagus nerves of adult male hooded rats. Injections of 30% HRP were made into the muscle wall of the fundus and antrum regions of the stomach. After 48 hr survival time, animals were perfused intracardially with a phosphate buffer plus sucrose wash followed by glutaraldehyde and paraformaldehyde fixative. The brain stem, spinal cord and corresponding dorsal root ganglia, superior cervical sympathetic ganglion, and the nodose ganglion were removed and cut into 50 micron sections. All tissue was processed with tetramethylbenzidine (TMB) for the blue reaction according to Mesulum and counterstained with neutral red. Sequential sections were examined under a microscope. Labeled neurons and nerve terminals were identified using bright and dark field condensers and polarized light. In tissue from animals that had HRP applied to the cervical vagus nerves, retrogradely labeled neurons were identified ipsilaterally in the medulla located in the dorsal motor nucleus of the vagus (DMN) and the nucleus ambiguus (NA). Labeled cells extended from the DMN into the spinal cord in ventral-medial and laminae X regions C1 and C2 of cervical segments. Many neurons were labeled in the nodose ganglion. Anterogradely labeled terminals were observed throughout and adjacent to the solitary nucleus (NTS) dorsal to the DMN and intermixed among labeled neurons located in the DMN. In tissue from animals that had HRP applied to the esophageal vagus nerves, similar labeling was observed. However, fewer neurons were identified in the NA, the nodose ganglion, and only in laminae X of the cervical spinal cord segments C1 and C2. Also, very little terminal labeling was observed in and adjacent to the NTS. Labeled neurons in tissue from animals that had HRP injected into the stomach wall were observed bilaterally in the DMN, nodose ganglion, and only in laminae X at the C1 and C2 levels of the spinal cord. Labeled neurons also were observed in the dorsal root ganglia of the thoracic cord. These data indicate that cervical cord and NA neurons are important in the supradiaphragmatic motor innervation by the vagus. Also, many afferents to the NTS originate above the diaphragm. In addition, some afferents from the stomach enter the central nervous system via the thoracic spinal cord.

Animals↗

Effect of nolinium bromide on vascular smooth muscle.

Nolinium bromide inhibits gastric acid secretion and gastrointestinal smooth muscle contraction. While the compound's gastric antisecretory action has been attributed in part to inhibition of gastric adenylate cyclase and the gastric proton-transport ATPase, the mechanism of nolinium bromide's relaxant effect on smooth muscle has not been elucidated. We have determined that nolinium bromide inhibits contraction of vascular smooth muscle, using isolated rabbit aortic strips. This report characterizes the specificity of this inhibition (by using several agonists) and its Ca2+ dependence (by using contractile conditions of known dependence on various Ca2+ pools). Nolinium bromide (50-200 microM) was a reversible, insurmountable inhibitor of contractions induced by Ca2+ (in 40 mM KC1 depolarizing medium) and norepinephrine, with IC50 values of 96 and 118 microM, respectively, for suppression of maximum contractile force. Contractions in response to Asn1Val5-angiotensin II in both 2.5 mM Ca2+ and 0 mM Ca2+ medium were also inhibited (IC50 value = 110 microM under both conditions). Initial contraction rates for all these conditions were depressed by nolinium bromide. Nolinium bromide inhibited equally the phasic (internal Ca2+-dependent) and tonic (external Ca2+-dependent) components of norepinephrine-induced contractions. These results extend the muscle relaxant profile of nolinium bromide to include, albeit with low potency, vascular smooth muscle, and show that its potency is similar in inhibiting the contractile response to three different stimuli: angiotensin II, Ca2+, and norepinephrine.

Angiotensin II↗

Red-cell amino acid transport. Evidence for the presence of system ASC in mature human red blood cells.

The properties of Na+-dependent L-alanine transport in human erythrocytes were investigated using K+ as the Na+ substitute. Initial rates of Na+-dependent L-alanine uptake (0.2 mM extracellular amino acid) for erythrocytes from 22 donors ranged from 40 to 180 mumol/litre of cells per h at 37 degrees C. Amino acid uptake over the concentration range 0.1-8 mM was consistent with a single saturable component of Na+-dependent L-alanine transport. Apparent Km and Vmax. values at 37 and 5 degrees C measured in erythrocytes from the same donor were 0.27 and 0.085 mM respectively, and 270 and 8.5 mumol/litre of cells per h respectively. The transporter responsible for this uptake was identified as system ASC on the basis of cross-inhibition studies with a series of 42 amino acids and amino acid analogues. Apparent Ki values for glycine, L-alpha-amino-n-butyrate, L-serine and L-leucine as inhibitors of Na+-dependent L-alanine uptake at 37 degrees C were 4.2, 0.12, 0.16 and 0.70 mM respectively. Reticulocytes from a patient with inherited pyruvate kinase deficiency were found to have a 10-fold elevated activity of Na+-dependent L-alanine uptake compared with erythrocytes from normal donors. Separation of erythrocytes according to cell density (cell age) established that even the oldest mature erythrocytes retained significant Na+-dependent L-alanine transport activity. Amino acid transport was, however, a more sensitive indicator of cell age than acetylcholinesterase activity. Erythrocytes were found to accumulate L-alanine against its concentration gradient (distribution ratio approx. 1.5 after 4 h incubation), an effect that was abolished in Na+-free media. Na+-dependent L-alanine uptake was shown to be associated with L-alanine-dependent Na+ influx, the measured coupling ratio being 1:1.

Alanine↗

Demonstration of active potassium secretion in the late distal tubule.

Studies were performed in the rat, under steady-state conditions, to determine the mode of potassium transport in the late distal tubule. In these experiments the potential difference and potassium activity were measured simultaneously in steady-state fluid droplets in control rats, during acute infusion of KCl, and in potassium-deficient rats. The results demonstrate active potassium secretion in the late distal tubule of the control and KCl-infused animals, since the observed potassium activity of 11.14 +/- 1.39 in control animals and 25.26 +/- 2.96 meq/liter in potassium-loaded animals was significantly greater than the predicted values of 7.75 +/- 0.59 and 14.01 +/- 0.94 meq/liter in the same groups, respectively. In potassium-deficient animals, however, the observed potassium activity in luminal fluid of 4.03 +/- 0.55 meq/liter was not different from the predicted value of 4.26 +/- 0.32. In summary, this study demonstrates that potassium secretion in the late distal tubule of the rat occurs by an active process and fails to demonstrate active absorption in the same tubular segment.

Animals↗

Phosphate content of mammalian neurofilaments.

The phosphate content of neurofilaments from bovine spinal cord and of their constituent polypeptides was determined. Neurofilament preparations, as isolated, contained substantial amounts of phosphate, having between 65 and 98 nmol of phosphate/mg of protein. When the polypeptides of the neurofilament were assayed for phosphate individually, the 210,000-and 160,000-dalton polypeptides were found to possess large numbers of phosphate groups, while the 68,000-dalton polypeptide had less than 1 mol of phosphate/mol of polypeptide. The 210,000-dalton polypeptide had about 104 mol of phosphate bound/mol of polypeptide, and the 160,000-dalton polypeptide had about 26 mol of phosphate/mol of polypeptide. This distribution of phosphate among the polypeptides of the neurofilament preparation was qualitatively confirmed when sodium dodecyl sulfate-polyacrylamide gels of the preparations were stained for phosphate. Bands corresponding to the 210,000- and 160,000-dalton polypeptides were readily detected. No other phosphate-stained bands were seen, even on heavily loaded gels.

Animals↗

Social crowding enhances aversiveness naloxone in rats.

If endorphins mediate various behavioural states including reactions to stress and social affect, then experimental manipulation of such states should alter the stimulus properties of opioid antagonists. The results of experiments in which the aversiveness of naloxone was increased by chronic environmental stress produced by rearing and maintaining male rats under conditions of severe social crowding, support this theoretical proposition. All rats acquired aversions to flavoured solutions that had been presented for 15 min immediately prior to a systemic injection of naloxone. The degree of the conditioned aversion was greater in rats maintained in crowded conditions. Transferring rats from crowded conditions to individual accommodation 3 weeks before the start of aversive conditioning did not attenuate the increased aversiveness of the antagonist. It is suggested that social interaction under conditions of chronic crowding induces a prolonged increase in the level of tonic activity in endorphinergic systems.

Animals↗

Effect of haemorrhage on renin concentration in superficial and deep venous outflows of the cat kidney.

1. Plasma renin concentration is significantly higher in the subcapsular venous outflow, which drains the superficial cortex, than in the deep venous outflow, which drains the inner half of the cortex and medulla of the cat kidney. The purpose of these experiments was to observe whether this pattern is preserved or disrupted by a stimulus to renin release. 2. Plasma renin concentration in arterial samples and in the superficial and deep renal venous outflows was measured before and after haemorrhage which produced a 24 +/- 6.7% drop in mean blood pressure in 13 cats. 3. After haemorrhage, total kidney plasma flow and glomerular filtration rate (GFR) did not change significantly. There was a rise in arterial plasma renin concentration. Venous minus arterial plasma renin concentration increased significantly in the deep venous outflow, but not in the superficial outflow. 4. The results suggest that both superficial and deep cortical venous drainage of the cat kidney should be considered when measuring renal renin release. In addition, they suggest that there may be differences in the response of superficial and deep juxtaglomerular apparatuses to haemorrhage.

Animals↗

Inactivation or elimination of potentially trypanolytic, complement-activating immune complexes by pathogenic trypanosomes.

Trypanosoma brucei subsp. brucei and T. congolense incubated in homologous antibody at 0 degrees C for 30 min were lysed by subsequent addition of guinea pig complement. Trypanosomes incubated in antibody at 37 degrees C before complement treatment remained intact. Parasites bearing adsorbed antibody also remained intact when incubated at 37 degrees C before complement treatment. The proportion of cells which survived complement treatment decreased with increasing antibody concentration. Parasites which survived complement treatment continued to express antigens which could bind complement-activating antibody, but did not bear complement-activating immune complexes. Virtually all cells in T. brucei populations exposed to antibody at 37 degrees C, but only 10(-3) to 10(-5) of the cells in populations exposed to antibody at 0 degrees C before complement treatment, remained infective for X-irradiated mice. Only 10(-6) to 10(-7) of T. brucei populations exposed to antibody at 0 or 37 degrees C before complement treatment infected mice immunized with homologous antigens. Serotype analysis of substrains and of T. brucei populations isolated from mice infected with antibody and complement-treated parasites suggested that variant-specific antigens participated in trypanolysis and that T. brucei which survived complement treatment could undergo antigenic variation. Mechanisms by which trypanosomes may inactivate or eliminate surface immune complexes and the possible significance of this phenomenon in trypanosomiasis are discussed.

Animals↗

Regional renin release by the cat kidney in vitro and in vivo.

Differences in the rate of renin release by superficial and deep areas of the cat kidney cortex were studied in vitro and in vivo. Renin release in vitro by outer cortical slices was significantly higher than by their inner counterparts: 19.6 +/- 2.3 vs. 12.8 +/- 1.95 ng angiotensin I-h-1-mg fresh tissue-1-h of incubation-1. In vivo blood was sampled from subcapsular (outer cortical) and deep (inner cortical and medullary) renal venous circulation from anesthetized cats. Renal venous minus arterial plasma renin concentration was respectively, 4.3 +/- 1.12 and 1.9 +/- 1.04 ng angiotensin I-ml-1-h-1 (P less than 0.01). By assuming that in these experiments renal blood flow distribution was approximately equal to each of the two areas of venous drainage, as reported in the isolated perfused cat kidney, we infer from the regional differences in arteriovenous concentration that the rate of renin release of the outer cortex is higher than that of the innder cortex in the cat kidney in vivo. Tissue content of renin was found to decrease toward the deep cortex. The results support the concept that the rate of regional renin release correlates with tissue renin content, at least under the conditions of the present experiments.

Animals↗

Non-clostridial gas gangrene in the diabetic lower limb.

Three cases of non-clostridial gas gangrene in diabetic lower limbs are reported. This rare condition occurs only in diabetes with peripheral neuropathy and is invariably fatal unless treated surgically. The clinical picture is deceptive with a slow, but insidiously progressive course, and the late appearance of skin necrosis. Antibacterial therapy is ineffective in preventing death. A serious delay may be fostered by inconclusive bacteriological investigations. Urgent radical amputation is required to save the patient's life.

Adult↗

Behçet's syndrome with perforations of the colon.

A case of Behçet's syndrome with mucosal ulcerations of the ascending colon and three perforations of the caecum is described. It is the first documented case of this syndrome where colitis has occurred without concomitant rectal lesions. The reported cases of Behçet's syndrome with associated colonic lesions make up a heterogeneous group. It is suggested that the different patients may have suffered from pathogenetically different diseases.

Adult↗