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Biomedical subjects

J H Scott

Publications and source records attributed to J H Scott.

At least 19 recordsLinked to original sources

Lateral mass fusion for lower back pain.

Forty patients who underwent Wiltse's lateral mass fusion by two different surgeons for spondylolisthesis or degenerative disc disease have been independently reviewed. It was found at follow-up (mean 22 months +/- S.D. 14 months) that factors that affected the final result were the age of the patient, the presence of preoperative nerve root symptoms, previous disc surgery, and incomplete fusion. The duration of symptoms, length of follow-up, preoperative spondylolysis, and the extent of the fusion did not appear to affect the result. This series confirms the previous reports that Wiltse's mass fusion is a good technique for relieving pain in the majority of patients.

Adolescent

Specific antibody synthesis and biliary secretion by the rat liver after intestinal immunization with cholera toxin.

This study was designed to investigate the location, specificity, and significance of antibody-containing cells in the liver. After intestinal administration of cholera toxin, high numbers of specific antibody-containing cells appeared in the liver during the early priming period and after boosting. In contrast, a significant number of specific antibody-containing cells appeared in the lamina propria of the intestine only after boosting. In the liver, the specific antibody-containing cells were predominantly located in the sinusoidal region of zone 1 of the liver lobules. About 80% of the specific antibody-producing cells in the liver synthesized anticholera toxin antibody of the immunoglobulin A class. During the priming period, the concentration of immunoglobulin A anticholera toxin in bile paralleled the increase and decrease in the number of specific antibody-containing cells in the liver. Liver perfusion experiments indicated that during the priming period at least 70% of the biliary immunoglobulin A anticholera toxin antibody was synthesized within the liver, whereas 30% was synthesized in the liver after boosting. Thus, during the early immune response, the liver seems to be the major source for specific biliary antibody to intestinally administered cholera toxin.

Animals

Bone scintigraphy in symptomatic spondylolysis.

In 66 patients with back pain and suspected spondylolysis, the results of bone scintigraphy have been correlated with operative findings and clinical follow-up. Although bone scintigraphy is of little value for primary diagnosis, it helps to distinguish between those patients with established non-union of the defect, and those in whom healing is still progressing and who may benefit from immobilisation. We also found that increased uptake on the contralateral side to a unilateral spondylolysis is suggestive of impending fracture.

Adolescent

Induction of immune tolerance by administration of monoclonal antibody to L3T4.

Immune responses can be profoundly altered in mice by treatment with monoclonal antibodies (MAb) to L3T4, the mouse homologue for the CD4 antigen in humans. Treatment of mice with anti-L3T4 blocks both primary and secondary immune responses, delays allograft rejection, and retards autoimmunity. To determine whether anti-L3T4 could also be used to induce tolerance, we investigated the effect of treatment with rat MAb to L3T4 on the immune response to two other rat MAb: MAb to chicken egg ovalbumin (OVA) and MAb to T200, an antigen expressed on all mouse mononuclear blood cells. Treatment with anti-L3T4 prevented the primary humoral response to both of these MAb. Moreover, the anti-L3T4 MAb induced tolerance to itself, and it induced tolerance to the anti-OVA MAb when the two MAb were given concurrently. However, anti-L3T4 did not induce tolerance to the anti-T200 MAb when these MAb were given concurrently. These findings indicate that treatment with MAb to L3T4 may provide a new method for inducing tolerance to some, but not all, antigens. Because L3T4 in mice is homologous to CD4 in humans, our findings suggest that it may be possible to use anti-CD4 to induce tolerance to specific xenogeneic MAb, thereby facilitating their use as therapeutic agents in people.

Animals

Lytic spondylolysis. Repair by wiring.

A technique for repairing the defect in spondylolysis by wiring is presented together with the results achieved in seven patients; the follow-up ranged from 2 to 12 years. The relative simplicity of the technique is stressed; and the technical problems likely to be encountered, together with the modifications of the basic technique necessary to cope with them, are noted. When conservative methods have been tried without success and the patient has a lesion at one or more levels and is less than 30 years old at presentation, then the technique described will give predictable results with regard to union of the defect and patient function.

Adolescent

Rejection of skin grafts and generation of cytotoxic T cells by mice depleted of L3T4+ cells.

In mice, "helper/inducer" T cells can be depleted by treatment with a rat monoclonal antibody to the cell surface antigen, L3T4, which is homologous to the human antigen T4 (CD4). In order to examine the contribution of "helper/inducer" T cells to cellular immunity, C57BL/6 (H-2b) mice were treated weekly with 1 mg i.v. of a monoclonal antibody to L3T4. Three days after the first injection, the mice received skin grafts from BALB/c (H-2d) mice. The mice were then examined for skin graft rejection and for the development of cytotoxic cells. Treatment with anti-L3T4 prolonged skin graft survival from 9 to 18 days. Graft rejection was associated with the development of cellular cytotoxicity against H-2d targets. Cytotoxicity developed despite greater than or equal to 90% depletion of splenic L3T4+ cells. Allospecific cytotoxic T cells could also be generated in vitro from C57BL/6 spleen cells depleted of L3T4+ cells, when these were exposed in a mixed leukocyte culture to irradiated, T-cell-depleted, BALB/c spleen cells. In a mixed leukocyte culture using responder spleen cells from untreated C57BL/6 mice, both proliferation and interleukin 2 production were inhibited in the presence of antibody to L3T4 and, to a lesser extent, by antibody to Lyt-2. Complete inhibition was achieved by the presence of both antibodies. In a mixed leukocyte culture using responder spleen cells from C57BL/6 mice that had been treated with anti-L3T4, both proliferation and interleukin 2 production were inhibited largely by antibody to Lyt-2, although the presence of both anti-Lyt-2 and anti-L3T4 was most inhibitory. These findings indicate that graft rejection and cellular cytotoxicity can be generated in mice depleted of L3T4+ cells by methods that have previously been shown to abrogate humoral immunity. Cellular immunity appears to require few, if any, L3T4+ cells. These findings have implications for the clinical use of antibodies to "helper/inducer" T cells.

Animals

Purification of synexin by pH step elution from chromatofocusing media in the absence of ampholytes.

Synexin can be purified to virtual homogeneity by a modification of the conventional chromatofocusing technique. Ampholytes are omitted from the procedure altogether and the protein is eluted by a specific pH step chosen on the basis of the pI of the protein. This modification of the conventional method eliminates the separation of ampholytes from the purified protein, an insurmountable problem in our case, and reduces the cost of purification profoundly.

Adrenal Medulla

Synexin binds in a calcium-dependent fashion to oriented chromaffin cell plasma membranes.

Oriented plasma membrane fragments from chromaffin cells, isolated on polylysine-coated polyacrylamide beads, bind synexin in a calcium dependent manner. Synexin binding was also detected on beads coated with chromaffin granule membranes, but not to beads coated with erythrocyte membranes or to uncoated beads. Synexin binding to plasma membrane coated beads showed a specific requirement for calcium (K1 2 = 200 microM) and was insensitive to other divalent cations such as magnesium, strontium and barium. Synexin binding to either plasma membrane or granule membrane coated beads was saturable, was partially reversible by EGTA and was directly observed by SDS-polyacrylamide gel electrophoresis.

Adrenal Medulla

An osmotic mechanism for exocytosis from dissociated chromaffin cells.

Dissociated chromaffin cells from bovine adrenal medulla were stimulated to secrete epinephrine and dopamine beta-hydroxylase with a variety of secretagogues in a study designed to test the hypothesis that the chemiosmotic lysis reaction of isolated chromaffin granules might in some way be related to the mechanism of release during exocytosis. Increasing the osmotic strength of the incubation medium with either NaCl or sucrose led to suppression of secretion of epinephrine from the cells regardless of whether secretion was induced with veratridine or acetylcholine. Suppression of secretion was approximately exponential with respect to osmotic strength. Epinephrine secretion occurred only if the medium contained a permeant anion such as chloride, and secretion induced by veratridine was suppressed when Na isethionate replaced NaCl in the medium. In an extensive study with different monovalent anions veratridine supported epinephrine secretion according to the following activity series: Br-, I-, NO3- greater than methylsulfate, SCN- greater than Cl greater than acetate much greater than isethionate. A similar series, except for the potency of NO3-, was observed with A23187 as agonist. In general, the anion series for granule lysis was analogous. However, there was a poor quantitative correlation between the anion dependence of chemiosmotic granule lysis and the anion dependence of cell secretion. Anion transport inhibitors such as probenecid and pyridoxal phosphate also inhibited secretion while the stilbene disulfonates were inactive. The ineffectiveness of the stilbene disulfonates further distinguished chemiosmotic granule lysis from cell secretion. Secretion of catecholamines, induced by veratridine or nicotine, a cholinergic agonist, was suppressed when NaCl in the medium was replaced by isosmotic sucrose and unexpectedly low levels of dopamine beta-hydroxylase were observed in some cases. In sum, these properties of secreting chromaffin cells resembled some properties of isolated chromaffin granules incubated in ATP and Cl-, but were different in a number of instances. We, therefore, have interpreted our data to indicate that while some mechanistic relationships may indeed exist between the release event in exocytosis from chromaffin cells and the chemiosmotic lysis reaction characteristic of isolated chromaffin granules, an understanding of the energetics of exocytosis awaits the discovery of reasons for the quantitative differences between the two systems.

Adrenal Medulla

Inhibition of synexin activity and exocytosis from chromaffin cells by phenothiazine drugs.

Synexin activity was found to be inhibited by low concentrations of the phenothiazine drugs, trifluoperazine and promethazine. Both drugs were also similarly effective at blocking nicotine and veratridine-induced catecholamine secretion from cultured chromaffin cells. These data thus indicate that synexin may be a target of phenothiazine drugs when they block secretion from chromaffin cells.

Adrenal Medulla

The management of testicular torsion in the acute pediatric scrotum.

From July 1976 through June 1981, 51 children with acute scrotal pain and swelling underwent surgical exploration. Testicular torsion (27 cases) and torsion of an appendage (18 cases) were the most common diagnoses. In the group with testicular torsion 5 testes were considered unsalvageable and these were removed. The remaining 22 testes, including those of questionable viability, were left in place. The early salvage rate of 81 per cent decreased to 50 per cent due to testicular atrophy found in the late followup period. The attempt to salvage all testes except those with obvious necrosis resulted in minimal morbidity. This approach is discussed in view of recent reports of long-term damage to the contralateral testis when an ischemic testis is not removed initially.

Acute Disease

Abnormal urinalysis in appendicitis.

In a retrospective review of 100 consecutive patients (50 adults and 50 children) with acute appendicitis we correlated abnormal urinalysis (positive occult blood and more than 4 red or white blood cells per high power field) with the operative findings. Abnormal results on urinalysis were noted in 18 adults and 12 children. All urine specimens were collected by the clean-catch method. Abnormal findings were found more frequently in female patients. A majority of patients (53 per cent) with abnormal results on urinalysis had a ruptured or inflamed appendix in proximity to the urinary tract.

Acute Disease