Search PubMed⌕ Search

Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 973 records · Page 54Linked to original sources
PubMed1988

Effect of uncouplers of oxidative phosphorylation on transmitter release in dystrophic mice.

Intracellular recording was used to study the effect of uncouplers of oxidative phosphorylation on miniature endplate potentials (m.e.p.p.s) in skeletal muscles from dystrophic mice and their clinically normal littermates. Control m.e.p.p. frequency in muscles from dystrophic mice was not significantly different from normal. In the presence of the inhibitors 2,4-dinitrophenol (10(-4) M) or guanidine (5 X 10(-3) M) m.e.p.p. frequency was increased less in muscles from dystrophic mice than that in muscles from normal littermates. In contrast, raising the extracellular calcium concentration, depolarising nerve terminals with potassium or motor nerve stimulation all caused a similar increase in m.e.p.p. frequency in normal and dystrophic muscles. It is suggested that there is a difference in the way in which calcium is stored in dystrophic nerve terminals but that their ability to regulate free calcium is normal.

Animals↗
PubMed1988

Dominance in lambda S mutations and evidence for translational control.

Phenotypic analysis of a collection of point mutations in the lysis gene S of bacteriophage lambda indicates that many of the S alleles exhibit at least partially dominant character, suggesting that the S gene product (gpS) must oligomerize to achieve its lethal membrane effect. Moreover, mutations found 5' to the coding sequence also show a dominant character and appear to define a site, designated sdi (structure directed initiation) where mRNA secondary structure controls the choice of initiation codons. We propose that formation of the sdi structure occludes the consensus Shine-Dalgarno sequence and results in initiation at the Met3 codon, generating a lethal 105 residue polypeptide. The model predicts that, in the absence of the sdi stem-and-loop, initiation occurs at the Met1 codon, generating a 107 residue polypeptide, which is a non-lethal inhibitor of lysis. In support of the model, alteration of the first codon was achieved using site-directed mutagenesis, resulting in an S allele that is more lethal and induces lysis significantly sooner than the wild-type.

Amino Acid Sequence↗
PubMed1988

The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis.

Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly decreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.

Aged↗
PubMed1988

Experimental continent diversion.

Urinary diversion utilizing a continence-maintaining ileal valve has been performed in 12 canines. This procedure offers a simple surgical procedure and uses the diversion's internal fluid pressure to maintain continence. Of 12 canines with this continence-maintaining ileal valve, 11 remained continent at sacrifice. Operative complications were minimal and late complications occurred in 2 dogs. Histological evaluation of the diversionary tissues revealed slight changes in the mucosa of the ileal valve, with some flattening of the villi. This procedure may have a clinical role in urinary diversion for patients with pelvic malignancy or patients who need urinary diversion for other reasons.

Animals↗
PubMed1988

Adriamycin-vitamin E combination therapy for treatment of prostate adenocarcinoma in the Nb rat model.

Adriamycin used in combination with vitamin E (Tocopherol) was evaluated in the treatment of Nb rat prostate adenocarcinoma. Vitamin E has been shown to enhance the growth-inhibitory effects of adriamycin on human prostatic carcinoma cells in vitro. The adriamycin-vitamin E treatment groups had the lowest average final tumor volume, but the mortality rate was 57% (17/30). These results suggest that vitamin E may play a role in enhancing the cytotoxic effects of adriamycin, but may not have any protective effect on normal cells as previously suggested through in vitro methods.

Adenocarcinoma↗
PubMed1988

The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells.

The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 micrograms of TCDD/kg body weight or corn oil carrier alone. Two-thirds hepatectomies were carried out at 1 or 7 days after injection and chromosomal aberrations and mitotic indexes of the regenerating hepatocytes were scored 54 hr after hepatectomy. Liver sections from additional intact mice were studied for TCDD-hepatotoxicity at 1, 7 and 30 days after injection. The three high doses of TCDD caused hepatotoxicity with necrosis of liver cells and focal architectural collapse by 30 days after injection. No evidence was obtained of an increase in the frequency of chromosomal structural aberrations at doses that allowed sufficient mitotic activity for cytogenetic evaluation. We conclude that TCDD is not a clastogen for mouse hepatocytes, although high doses cause marked hepatocellular necrosis.

Animals↗
PubMed1988

Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia.

The colony-stimulating factors regulate growth, differentiation, and function of blood cells. The effect of granulocyte colony-stimulating factor (G-CSF) on myeloid leukemias is unique among colony-stimulating factors in driving the leukemic cells from a self-renewing malignant state to a mature differentiated phenotype with the concomitant loss of tumorigenicity. This property of G-CSF has led to suggestions that its absence is responsible for lack of differentiation of leukemic cells and that the therapeutic administration of G-CSF could reverse this defect and result in a cure for leukemia. Here we show that the gene coding for human G-CSF is localized to chromosome 17, bands q11.2-21. The translocation of the long arm of chromosome 17 at q12-21 to chromosome 15 is a specific abnormality occurring in a high proportion of, if not all, patients with acute promyelocytic leukemia, a disease characterized by undifferentiated myeloid cells and a dismal prognosis. Abnormalities of the regulation of a specific differentiation factor gene mediated by a specific chromosomal rearrangement may be directly implicated in the pathogenesis of human leukemia.

Chromosome Mapping↗
PubMed1988

Primary tumors and tumor-like lesions of the clavicle.

Fifty eight patients seen at Memorial Sloan-Kettering Cancer Center over a 50-year period were reviewed for lesions of the clavicle. A variety of malignant neoplasms, benign neoplasms, and tumor-like lesions were seen. There were 30 malignant neoplasms, the commonest of which were plasmacytomas, osteosarcomas, and Ewing sarcomas. There were five postradiation sarcomas. An unusual granulocytic sarcoma with dense sclerosis was described. Among the benign lesions were two osteochondromas, two hemangiomas, and a giant cell tumor secondary to Paget disease. The tumor-like lesions included six aneurysmal bone cysts and five eosinophilic granulomas. There were two patients with chronic sclerosing osteomyelitis and one each with sternocostoclavicular hyperostosis (Sonozaki syndrome) and condensing osteitis. An unusually large lesion of pseudogout and a large brown tumor were also included in the series.

Adolescent↗
PubMed1988

A microwell assay for anchorage independent cell growth.

We describe modifications of the conventional assay for anchorage independent growth of fibroblasts that enable the assay to be carried out in microwell plates, as opposed to the conventional Petri dishes. The microwell assay is a good discriminator of final EGF concentrations in the range 10-100 picograms/ml, and can be used to detect absolute amounts of EGF below 2 pg. Addition of TGF beta to EGF enhances colony formation in the microassay in the usual manner. We describe the use of this microassay to identify and map local production of transforming growth factor activity by the component pieces of individual chick embryos. Transforming activity was identified in all the stages tested (Hamburger and Hamilton stages 13-23). Highest levels were found near the mid-line of the embryo. No clear differences in the cranio-caudal axis have so far been identified. This technique will enable the spatial and temporal distribution of transforming activity throughout vertebrate embryos to be completely mapped. It seems likely that this mapping process will help elucidate the normal role of transforming growth factors in embryos.

Animals↗
PubMed1988

Heterogeneity in neoplastic cell populations in chronic lymphocytic leukaemia defined by immunoglobulin expression and secretion in vitro.

Neoplastic cell populations were prepared from peripheral blood and bone marrow samples of four patients with typical B-cell chronic lymphocytic leukaemia (CLL). Lymph node biopsies were also performed and used as a source of neoplastic cells for two of these patients. Using sensitive ELISA systems to determine unstimulated immunoglobulin (Ig) secretion of these tissue-derived populations in culture, a discrepancy between the nature of the secreted Ig products was found. Peripheral blood and lymph node-derived populations from each patient secreted both whole molecules of Ig and a large molar excess of Ig light chains (free LC), whereas all bone marrow-derived population secreted only free LC. The isotypic expression of intrinsic, cell-surface immunoglobulin (sIg), determined using immunofluorescence microscopy and flow cytometry, was, however, indistinguishable between different tissue-derived populations for any one patient. The absolute amounts of LC secretion were not markedly different between the tissue-derived populations (blood = 5.3 +/- 1.7; marrow = 3.5 +/- 1.3; lymph node = 11.5 ng per 2 X 10(7) cells per h) and thus failure of detection could not account for this discrepancy. Furthermore, the presence of sIgM and sIgD on each tissue-derived population indicated that all were at least capable of synthesizing whole Ig for membrane insertion. These results suggest that the assessment of a B-cell function, Ig secretion, is a valuable technique for determining small differences within neoplastic populations from individual patients. These functional differences may be related to the maturity of different cells within clonal populations.

B-Lymphocytes↗
PubMed1988

Transfer and maintenance of small, mobilizable plasmids with ColE1 replication origins in Legionella pneumophila.

With the mutagenesis of specific, virulence-associated genes of Legionella pneumophila as the eventual goal, methods for gene transfer to these bacteria were developed. Following the observations of others that conjugative, broad-host-range plasmids could be transferred from Escherichia coli to L. pneumophila at low frequency, we constructed a small mobilizable vector, pTLP1, which carries oriV from pBR322, oriT from pRK2, Kmr from Tn5, and an L. pneumophila-derived fragment to permit chromosomal integration. In triparental matings including an E. coli with a conjugative (Tra+) helper plasmid, kanamycin-resistance was transferred from E. coli to L. pneumophila. Southern hybridization of L. pneumophila transconjugants showed that pTLP1 was replicated autonomously. Additional matings of plasmids having deletions or substitutions of pTLP1 sequences confirmed that replication in L. pneumophila requires oriV only. pTLP1 was maintained in L. pneumophila with passage on medium containing kanamycin but was rapidly lost after passage on nonselective medium. This plasmid instability in L. pneumophila is most likely due to rapid generation of plasmid-free segregants because of plasmid multimerization and low plasmid copy number. We conclude that mobilizable pBR322-derived plasmids can be used as shuttle vectors to transfer cloned genes to L. pneumophila, a feature that can be exploited for the purposes of mutagenesis or genetic complementation.

Blotting, Southern↗
PubMed1988

The dexamethasone suppression test in relation to symptomatology: preliminary findings controlling for serum dexamethasone concentrations.

A diagnostically heterogeneous sample of psychiatric inpatients (n = 52) was administered the 1 mg dexamethasone suppression test (DST) shortly after hospital admission. Each was also assessed using the Hamilton Rating Scale for Depression (HRSD) and selected items of the Present State Examination (PSE) representing psychomotor retardation and anxiety. A potent determinant of postdexamethasone serum cortisol concentrations was found to be the level of serum dexamethasone concentration achieved following the oral dose. No relationship was found between postdexamethasone cortisol concentration and the scores on either the HRSD or an anxiety scale derived from selected PSE items. However, symptoms of psychomotor retardation were significantly related to postdexamethasone serum cortisol concentration, particularly when the serum dexamethasone concentrations were taken into account. It may be that DST nonsuppression in psychiatric patients is in part a reflection of the presence of psychomotor retardation, a phenomenon that cuts across diagnostic categories.

Adolescent↗
PubMed1988

Insulin and insulin-like growth factor-I can trigger the differentiation of catecholaminergic precursors in cultures of dorsal root ganglia.

Avian sensory ganglia contain a population of normally latent autonomic-type precursors with noradrenergic potentialities. Their differentiation in vitro into cells expressing tyrosine hydroxylase immunoreactivity is acutely dependent on the presence of one or more substances found in chick embryo extract (CEE). We have used cultures of dissociated dorsal root ganglia from embryonic quail as a model system in which to assay factors promoting catecholaminergic differentiation, the latter being appreciated quantitatively in terms of the number of tyrosine hydroxylase-positive cells present after 6 days in vitro; over a large range of concentrations, the number of such cells is directly proportional to the amount of CEE in the medium. In the course of attempts to replace CEE by defined bioactive molecules, we found that epidermal growth factor, fibroblast growth factor or nerve growth factor possessed negligible, or only marginal, noradrenergic differentiation-promoting activity. In contrast, insulin, at nanomolar levels, triggered expression of the catecholaminergic phenotype as well as did CEE. Insulin-like growth factor-I, at similar concentrations, had an analogous effect. It is suggested that an insulin-like molecule may play a role in the normal differentiation of sympathoblast precursors in vivo.

Animals↗
PubMed1988

Arterial helium embolism from a ruptured intraaortic balloon.

A 67-year-old man sustained a sudden global neurological deficit immediately following rupture of an intraaortic balloon catheter. Considerable improvement in his neurological function occurred during and after three hyperbaric oxygen treatments.

Aged↗
PubMed1988

Characteristics of protein sparing effect of total parenteral nutrition in the surgical infant.

To determine the best formula to prevent protein depletion, 31 surgical infants on intravenous (IV) diet were studied. The study was divided into two phases. Phase I diet included 5% glucose and 1.5% or 2% amino acid infusion; phase II diet consisted of 5% glucose and 1.5% or 2% aminoacid plus 10% Intralipid. In each phase, oxygen consumption, carbon dioxide production, and energy expenditure were determined. The utilization of carbohydrate, fat, and protein was calculated from urinary nitrogen excretion and nonprotein respiratory quotient. The mean caloric intake during phase I and phase II was 62 and 94 kcal/kg/d, respectively. A positive nitrogen balance was obtained in infants receiving fat-free total parenteral nutrition (TPN) with a mean protein intake of 2.6 g/kg/d and a mean energy intake exceeding the energy expenditure by 24%. Infusion of more calories as Intralipid (phase II) caused a significant reduction in protein oxidation, thus protein contribution to the energy expenditure and an increase in protein retention. We conclude that supplementation of low-calorie TPN diets with Intralipid increases protein sparing and is preferable to the administration of very high glucose loads.

Amino Acids↗