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Biomedical subjects

A Terry

Publications and source records attributed to A Terry.

35 records · Page 2Linked to original sources

A common proviral integration region, fit-1, in T-cell tumors induced by myc-containing feline leukemia viruses.

Feline leukemia viruses carrying transduced v-myc genes (myc-FeLV) induce tumors of clonal origin, suggesting that activated myc alone is not sufficient for tumorigenesis. To investigate the hypothesis that insertional mutagenesis plays a role by activating genes which collaborate with v-myc, we looked for evidence of common proviral integration sites in these tumors. By inverse polymerase chain reaction we identified a 6-kb domain, designated fit-1, in which FeLV proviruses were inserted in four of nine (44%) T-cell tumors induced by myc-FeLV. The fit-1 locus was mapped to feline chromosome B2 and appears to be distinct from known oncogenes located on this chromosome. Fit-1 represents a novel common proviral integration region which may harbor a cellular gene which acts in concert with the myc gene in T-cell tumorigenesis.

Animals↗

Orbital meningoencephalocele manifesting as a conjunctival mass.

Orbital meningoencephalocele is a rare congenital abnormality caused by a defect of the cranio-orbital bones that usually manifests soon after birth as a soft, cystic fullness in the superomedial canthal area with associated exophthalmos. We managed an unusual case of congenital orbital meningoencephalocele that manifested as a cystic conjunctival mass without proptosis or periorbital changes. Preoperative computed tomographic scans failed to demonstrate a bone defect. After suture ligature of the posterior stalk, excision of the lesion yielded an ependymal cyst surrounded by neuroglial and meningeal tissue and filled with cerebrospinal fluid. The patient had normal results of ophthalmic and neurologic examinations after transconjunctival resection of the lesion after three years of follow-up. An orbital approach may be appropriate for a few selected cases in which no bone defect is found on computed tomography. Orbital meningoencephalocele should be included in the differential diagnosis of isolated congenital conjunctival cystic masses.

Conjunctival Diseases↗

Pathogenesis of feline leukemia virus T17: contrasting fates of helper, v-myc, and v-tcr proviruses in secondary tumors.

A naturally occurring feline thymic lymphosarcoma (T17) provided the unique observation of a T-cell antigen receptor beta-chain gene (v-tcr) transduced by a retrovirus. The primary tumor contained three classes of feline leukemia virus (FeLV) provirus, which have now been characterized in more detail as (i) v-tcr-containing recombinant proviruses, (ii) v-myc-containing recombinant proviruses, and (iii) apparently full-length helper FeLV proviruses. The two transductions appear to have been independent events, with distinct recombinational junctions and no sequence overlap in the host-derived inserts. The T17 tumor cell line releases large numbers of FeLV particles of low infectivity; all three genomes are encapsidated, but passage of FeLV-T17 on feline fibroblast and lymphoma cells led to selective loss of the recombinant viruses. The oncogenic potential of the T17 virus complex was, therefore, tested by infection of neonatal cats with virus harvested directly from the primary T17 tumor cell line. A single inoculation of FeLV-T17 caused persistent low-grade infection culminating in thymic lymphosarcoma and acute thymic atrophy, which was accelerated by coinfection with the weakly pathogenic FeLV subgroup A (FeLV-A)/Glasgow-1 helper. Molecularly cloned FeLV-tcr virus (T-31) rescued for replication by a weakly pathogenic FeLV-A/Glasgow-1 helper virus was similarly tested in vivo and induced thymic atrophy and thymic lymphosarcomas. Most FeLV-T17-induced tumors manifested either v-myc or an activated c-myc allele and had undergone rearrangement of endogenous T-cell antigen receptor beta-chain genes, supporting the proposition that the oncogenic effects of c-myc linked to the FeLV long terminal repeat are targeted to a specific window in T-cell differentiation. However, neither the FeLV-T17-induced tumors nor the T-31 + FeLV-A-induced tumors contained clonally represented v-tcr sequences. Only one of the FeLV-T17-induced tumors contained detectable v-tcr proviruses, at a low copy number. While v-tcr does not have a readily transmissible oncogenic function, a more restricted role is not excluded, perhaps involving antigenic peptide-major histocompatibility complex recognition by the T-cell receptor complex. Such a function could be obscured by the genetic diversity of the outbred domestic cat host.

Animals↗

The source of pulsatile secretion of progesterone during the human follicular phase.

This study was designed to establish the normal pattern of serum progesterone and the origin of its secretion during the follicular phase of the normal menstrual cycle. In the first study, 12 normal women were studied on 3 occasions each at different times during a single follicular phase. Serum samples were collected every 10 min over 8 h, for 6 h before and 2 h after an injection of naloxone (5 mg iv). The mean serum progesterone remained constant (0.9 nmol/L) across the follicular phase until just before ovulation; individual subjects showed pulsatility of progesterone (1-6 pulses/6 h) but there was no relationship of this to LH pulsatility and no variation of progesterone pulsatility across the follicular phase. Naloxone caused an increase in the mean serum progesterone in the early follicular phase to 1.9 +/- 0.7 nmol/L and in the mid and late follicular phase to 2.1 +/- 0.7 nmol/L and 3.4 +/- 2.5 nmol/L, respectively. The second study was performed to assess the contribution of the residual corpus luteum and the developing follicle to the pulsatile secretion of progesterone. Seven anovulatory women with low levels of serum LH and absent LH pulsatility were studied before and after clomiphene (100 mg/day for 5 days) by collecting blood samples every 15 min for 6 h before GnRH (10 mg iv) and for 2 h afterwards. The anovulatory women had comparable mean serum concentration of progesterone (0.9 +/- 0.5 nmol/L) to normal women and similar frequency of progesterone pulsatility (2.1 +/- 1.1 pulses/6 h). After administration of clomiphene, there was no significant change in progesterone pulsatility (1.7 +/- 1.0 pulses/6 h) despite a substantial increase in LH pulsatility (from none to 3.0 +/- 1.0 pulses/6 h). There was no significant increase in serum progesterone after clomiphene or GnRH which both caused a substantial increase in serum LH. The third study involved eight normal women studied before and after treatment with dexamethasone (2 mg/day for 2 days) to assess the adrenal component of progesterone secretion. Blood samples were collected every 10 min for 6 h before and 2 h after naloxone (5 mg iv). Dexamethasone reduced serum progesterone to below assay sensitivity (less than 0.2 nmol/L) and obliterated progesterone pulsatility. The increase in serum progesterone and cortisol induced by naloxone was blocked by dexamethasone; the naloxone-induced rise of serum LH was not affected by dexamethasone. We conclude that neither the preceding corpus luteum nor the developing follicle are important contributors to the serum concentration of progesterone during the normal follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Activity Cycles↗

Liver transplantation in Langerhans' cell histiocytosis (histiocytosis X).

Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious osteolytic lesions at the time of transplantation. The histologic examination of the excised liver showed features consistent with primary sclerosing cholangitis. The two patients had an excellent recovery with no evidence of progression of LCH or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years after organ transplantation.

Adolescent↗

Comparison of CT scan muscle measurements and isokinetic trunk strength in postoperative patients.

The present study compared the computed tomography (CT) scan muscle area/muscle density and isokinetic trunk strength of a group of spinal surgery patients (35 males and 11 females) 3 months postoperatively. Analyses showed trunk strength means to be below 50% of gender-specific "normal" values obtained by evaluating a normative sample. Extensor strength was more significantly affected than flexors. Single-cut CT scans performed at the time of isokinetic trunk strength assessment demonstrated psoas and erector spinae atrophy through a significant decrease in muscle density, with only a trend towards decreased cross-sectional area. Findings also indicated that there was a significant correlation between increased mechanical trunk strength performance and greater muscle density on CT scan. Strength was significantly lower for the male patients undergoing spinal fusion compared with those undergoing disc excision. However, no significant difference was found in strength measures between: males with high versus low pain level and working versus nonworking males at the time of evaluation.

Adult↗

Pain provocation and disc deterioration by age. A CT/discography study in a low-back pain population.

The computed tomography (CT)/discograms and discographic pain provocation reports of 291 clinical patients, 790 discs (mean age, 38; range, 17-79) were collected. The CT/discograms were classified separating anular disruption and degeneration and recording the pain provoked during discography as no pain, dissimilar, similar, or exact reproduction of the patient's clinical pain. Nondegenerated discs usually were found to be painless, and deteriorated discs painful. The proportion of severely degenerated but painless discs increased with age, as did the discs producing dissimilar pain. This may help explain the poor correlation of low-back pain with radiographic degenerative changes reported in previous epidemiologic studies.

Adult↗

Quantifying postoperative deficits of physical function following spinal surgery.

This study evaluates the degree of objectively quantified physical deconditioning of spinal surgery patients. The object is to evaluate the data in terms of the pain and disability claimed by 35 male and 11 female patients three months after spinal surgery. Among the males, two subgroups (i.e., disc excision or spinal fusion) were evaluated. All patients reported subjective indices of pain/disability and completed quantified tests of lumbar motion, sagittal trunk strength, lifting capacity, and bicycle ergometry. In general, true lumbar motion was markedly restricted to 50%-60% and trunk strength means were below 50% of gender-specific normative values. There were similar deficits for lifting capacity. Those who had spinal fusions tended to perform poorly, with a relatively high incidence of pain/disability. There were no differences found between the male group and subgroups who were gainfully employed or had a brief period of disability prior to surgery or had low subjective pain/disability. These results indicate that a patient's subjective pain/disability were not a reliable measure of functional capacity by three months postoperatively. Regardless of working status, pain level, or brevity of disability, there was a significant loss of performance ability and risk of persistent dysfunction after surgical treatment.

Adult↗

Induction of kappa light chain synthesis in 70Z/3 B lymphoma cells by chemically defined lipid A precursors.

The murine B cell lymphoma 70Z/3 is a tumor line that resembles an early B cell. It responds to lipopolysaccharide by synthesizing kappa light chains, resulting in the appearance of surface IgM. We now demonstrate that this effect is triggered by the lipid A domain of lipopolysaccharide since a defined tetraacyl disaccharide 1,4'-bisphosphate precursor of mature lipid A, designated lipid IVA (Raetz, C. R. H., Purcell, S., Meyer, M. V., Qureshi, N., and Takayama, K. (1985) J. Biol. Chem. 260, 16080-16088), is fully active in stimulating kappa chain mRNA synthesis. In contrast, the monosaccharide lipid A precursor, lipid X, shows only slight activity; but a large excess of lipid X appears to complete with lipid IVA, partially blocking its effects. Mutants of the 70Z/3 line that are unresponsive to lipopolysaccharide also fail to respond to lipid IVA. The somatic cell system described here, coupled with the use of chemically defined agonists and antagonists, offers a new approach to understanding the early events in lipopolysaccharide/animal cell interactions.

Animals↗

Receptor-mediated leukaemogenesis: hypothesis revisited.

The discovery of the first example of retroviral transduction of an immunological effector molecule has led us to reconsider the possible importance of cell surface receptors of the immune system in leukaemia development. Antigen receptors on lymphoid cells not only bind external ligands but are crucial in the control of cellular proliferation. The concept of autocrine stimulation in oncogenesis is already well established and we see no reason to exclude the possibility of analogous mechanism operating through antigen receptors. At present, we are investigating the oncogenic function of the retrovirus (FeLV-T17) carrying a T-cell receptor gene (v-tcr). In addressing the general concept of oncogenesis by ligand/receptor interactions in the immune system we face the problem of the diversity and, for T-cell antigen receptors, the complex nature of receptor-ligand interaction. Nevertheless, the implications of the model encourage us to continue to search for new experimental tools and approaches to the question.

Animals↗

Interviewing the elderly about their health: validity and effects on family doctor contacts.

Health-related questions in a large interview schedule (designed to examine relationships between customary physical activity, physical and psychological well-being among the elderly) were found to be repeatable (overall agreement was 93%) when used by two independent interviewers. The sensitivity and specificity of the interview in discriminating between people with and without health problems were 80% and 92%, respectively, when compared with a physician's independent assessments. Family doctor case notes under-recorded many of the common health problems of elderly people and could not be used to validate the interviewees' responses. Comparisons between 41 interviewees and 75 age-, sex- and practice-matched controls demonstrated that interviewees were only slightly more likely to consult or request a repeat prescription in the week following the interview (19%) than controls (11%). The 95% confidence intervals of this 8% difference were wide (-6% to 22%) and it might well have occurred by chance. Practices intending to use screening or research interviews with elderly people should be reassured such activities are not associated with large increases in demand for their services.

Aged↗

Nocturnal intragastric therapy in type I glycogen storage disease: effect on hormonal and amino acid metabolism.

The acute hormonal and amino acid responses to differing food substrates were examined in type 1 glycogen storage disease. Ingestion of a glucose load or a glucose-plus-beef meal caused an acute fall in the initially elevated plasma glucagon, alanine, proline, and lactate. Ingestion of beef alone caused a sharp rise in these parameters. Long term nocturnal intragastric therapy of a high carbohydrate and moderate amino acid content resulted in a similar fall in these parameters as well as a fall in the elevated plasma glutamate, uric acid, triglycerides, and RBC-reduced glutathione. A remarkable clinical improvement and growth spurt accompanied the improvement in these biochemical values. The possible relation between the disturbed plasma hormonal and amino acid findings and growth failure and hyperuricemia is discussed.

Adolescent↗

Effect of expansion of extracellular fluid volume on renal phosphate handling.

To examine the specific effect of extracellular fluid (ECF) volume expansion on phosphate excretion studies were performed in thyroparathyroidectomized dogs receiving saline solution intravenously. The natriuresis resulting from ECF volume expansion was consistently accompanied by an increase in phosphate excretion. The possible role of increased filtered load of phosphate was eliminated in experiments in which the filtered load of phosphate was reduced by acute reduction in the glomerular filtration rate. Despite considerable reductions in filtered phosphate, ECF volume expansion resulted in a consistent increase in phosphate excretion. Furthermore, the possible contribution of alteration in blood composition was investigated in experiments in which saline was infused during thoracic inferior vena cava constriction. In these experiments saline infusion failed to increase sodium or phosphate excretion. Cessation of saline infusion and release of caval constriction resulted in a prompt natriuresis and increased phosphate excretion. It is concluded from these studies that extracellular fluid volume expansion results in an increased phosphate excretion in the parathyroidectomized dog. This effect is the specific consequence of ECF volume expansion and is not due to increase in the filtered load of phosphate or alterations in blood composition.

Animals↗