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Biomedical subjects

P A Singer

Publications and source records attributed to P A Singer.

At least 163 records · Page 9Linked to original sources
PubMed1984

Eo: a history of a mutation.

Eighteen mouse t haplotype-carrying strains were found not to express cell-surface E molecules controlled by class II genes of the H-2 complex (= Eo strains). Northern and Southern blot analysis of these and other, non-t strains that also fail to express the E molecule, has revealed two kinds of defect. Three strains (CRO437, tw2, and presumably to) were found to transcribe the E alpha gene, but they were not able to convert the message into a functional protein. All other Eo strains fail to transcribe the E alpha gene because of a deletion encompassing the promoter region, the RNA initiation site, and the first exon. The length of the deletion is approximately 650 +/- 50 bp. These two defects closely resemble those found previously in standard inbred strains carrying the H-2f, H-2q (failure of E mRNA to be expressed functionally), H-2b, and H-2s (deletion of a part of the E alpha gene) haplotypes. In particular, the location and length of the E alpha deletion appear to be the same in the strains carrying this mutation. The E alpha deletion is in linkage disequilibrium with certain alleles at other H-2 loci in some of the strains. These observations, combined with the growing evidence that H-2 haplotypes associated with t chromosomes derive from a single ancestral haplotype, suggest that the E alpha deletion is an old mutation and that it has been disseminated in mouse populations by the t chromosomes.

Animals↗
PubMed1983

Fasting increases glucose and leucine uptake during regeneration of the hypoglossal nerve in the rat.

Glucose uptake is increased during motoneuron regeneration. Since this glucose is probably used as an energy source for axonal regeneration we postulated that hypoglycemia might interfere with motoneuron regeneration. In order to partially test this hypothesis we attempted to induce moderate hypoglycemia by fasting rats for 3 days between the time of hypoglossal nerve transection and the time of [14C]2-deoxyglucose (2-DG) and [14C]leucine measurement. We transected one hypoglossal nerve, leaving the other intact, and measured the glucose uptake quantitatively or leucine uptake semiquantitatively in the hypoglossal nucleus. We found that both glucose and leucine uptake were increased in the hypoglossal nuclei during regeneration of the nerve in the fasted animals above that in the normally fed animals. This suggests that fasting creates a deficit of glucose and perhaps leucine which induces increased uptake.

Animals↗
PubMed1982

Blockade of retrograde axonal transport delays the onset of metabolic and morphologic changes induced by axotomy.

Axotomy-induced increase in 2-deoxyglucose (2-DG) uptake by motor nuclei and neuronal chromatolytic changes were studied after subepineural injection of colchicine into the motor nerve. Hypoglossal nuclei of either cats or rats were axotomized bilaterally, while one of the nerves was injected with colchicine or saline proximal to the site of nerve transection and the other was left intact or injected with saline. Colchicine abolished or decreased the uptake of 2-DG by axotomized nuclei and delayed the onset of chromatolysis. The decrease in 2-DG uptake was observed in rat hypoglossal nuclei between 24 and 48 hr but not 5 days after drug treatment. In turn, a delay in the onset of chromatolysis was observed in cat hypoglossal nuclei at 14 days but not 30 days after treatment. Saline did not prevent chromatolysis nor the increased uptake of 2-DG. Colchicine injected intraneurally in intact preparations did not result in chromatolysis or in increased 2-DG uptake. Following colchicine injection, the drug remained localized near the site of injection and blocked retrograde axonal transport of horseradish peroxidase in the hypoglossal nerve. These findings suggest that the onset of chromatolysis and of the increase in 2-DG uptake after axotomy are partly dependent upon retrograde axonal transport.

Afferent Pathways↗
PubMed1981

Retrograde axonal transport mediates the onset of regenerative changes in the hypoglossal nucleus.

The hypoglossal nucleus was assayed for [14C]2-deoxyglucose uptake 24 h after axotomy with and without colchicine injections into the nerve proximal to the nerve transection. Colchicine effectively blocked the usual increase in [14C]2-deoxyglucose uptake seen after axotomy. The drug also blocked the transport of horseradish peroxidase from the tongue muscles to the hypoglossal nucleus which otherwise occurred within this time period. Distribution of [3H]colchicine showed that the drug remained localized within the nerve close to the injection point. These results suggest that retrograde axoplasmic flow is involved in the mechanism which initiates hypoglossal neuron regeneration.

Animals↗
PubMed1980

Different species of messenger RNA encode receptor and secretory IgM mu chains differing at their carboxy termini.

Biosynthetic studies in the presence of an inhibitor of glycosylation indicate that individual human lymphoma-derived cell lines can synthesize both membrne receptor and presumptive secretory forms of IgM mu chains. The receptor form has a larger polypeptide chain than the secretory form and possesses a different C-terminus, but similar N-terminus, consistent with the presence of a C-terminal hydrophobic "tail" for integral membrane binding. Messenger RNA isolated from these cells directs the synthesis of both forms of mu chains in a wheat germ translation system, indicating the presence of independent mRNAs for each form. It is proposed that the synthetic pathways for receptor and secretory IgM diverge at the post-transcriptional level, possibly by differential RNA splicing to give mRNA molecules with or without a translatable "tail" segment.

Amino Acid Sequence↗
PubMed1980

Cell surface immunoglobulin mu and gamma chains of human lymphoid cells are of higher apparent molecular weight than their secreted counterparts.

Selected human lymphoma-derived and lymphoblastoid cell lines have been characterized and shown to be useful model systems for the expression of either cell surface Ig, or secretory Ig, or both simultaneously. Daudi and Raji cell lines were shown to express surface IgM with no secretion of IgM. The lymphoblastoid cell lines Tay-3 and RPMI 1788 are high-rate secretors of IgM. The lymphoma cell line BJAB synthesizes both cell surface IgM and secretory IgM. In the secreting cells, we have identified an intracellular mu chain with an apparent molecular weight approximately 2000 less than secreted mu chain. In cells synthesizing surface IgM, a surface mu chain has been identified which has an apparent mol. wt. of approximately 2000 more than secreted mu chain. The intracellular mu chain in these cells is indistinguishable in size from the mature surface mu chain; the Daudi cell line is exceptional in that surface deposition of the intracellular mu chain is preceded, or accompanied, by an increase in apparent mol. wt. The lymphoblastoid cell line Bec-11 synthesized both cell surface IgG and secretory IgG. In Bec-11 cells, a surface form of gamma chain, having a higher apparent mol. wt. than secreted gamma chain, has been resolved. There is no detectable difference between L chains associated with any of the different forms of H chain. A biosynthetic relationship between the different forms of H chain is proposed.

Cell Membrane↗
PubMed1979

A novel interaction involving a polypeptide chain (P33) in covalent linkage with IgM on the surface of a Burkitt lymphoma cell line (Daudi).

The surface IgM of Daudi Burkitt lymphoma cells has been shown to consist of mu chains and kappa chains covalently linked, by disulfide bonding, to a novel polypeptide chain of approximate molecular weight 33,000. This novel polypeptide chain (P33) is similar in several properties to the heavy chain of the Ia antigen: glycoprotein nature; apparent molecular weight; isoelectric behavior and cysteine content. The linkage of P33 to surface immunoglobulin has not been observed with any other human lymphoma or lymphoblastoid cell lines.

Binding Sites↗
PubMed1978

Transient TRH deficiency after prolonged thyroid hormone therapy.

A patient who had been treated with large doses of thyroid hormone for several years developed features of secondary hypothyroidism after thyroid hormone withdrawal. These findings were low serum T4 (3.8 micrograms/dl), T3 (23 ng/dl), and a failure of serum TSH to rise after TRH injection. Serum PRL values rose normally after TRH administration, and evaluation of other pituitary hormones was normal. When retested 3 months later, at which time the serum T4 was 5.5 micrograms/dl, the patient was somewhat less hypothyroid and there was an exaggerated TSH response to exogenous TRH, indicating recovery of pituitary TSH reserve. Indirect assessment of endogenous TRH reserve capacity was consistent with impairment of endogenous TRH activity. Repeat studies performed 7 months later indicated some improvements in this indirect assessment of endogenous TRH reserve capacity but a continued exaggerated TSH response to exogenous TRH administration. Further testing at 28 months revealed a serum T4 value of 7.8 micrograms/dl and a serum T3 value of 141 ng/dl. At this time, the TSH response to TRH was normal and the patient was considered fully recovered. A causal relationship between high doses of thyroid hormone and the presumptive impairment of endogenous TRH reserve is suggested.

Adolescent↗
PubMed1976

A hot wire device for cutting tissue culture flasks.

A small hot wire device for cutting plastic culture was can be constructed of steel rod, brass screws, nichrome wire and acrylic plastic sheeting and tubing. The nichrome wire is heated using a variable power transformer. Four sequential cuts are made in the culture flask bottom and the bottom separated from the remainder of the flask. Cultures can be stained, air-dried and cover slips affixed with PVP or epoxy resin. This method of cutting culture ware avoids the formation of small bits of polystyrene generated by rotating discs or saws.

Culture Techniques↗
PubMed1976

Associated systemic factors in cerebrovascular ischemia.

Systemic disorders (eg, cardiac, hematologic) are commonly recognized as predisposing and sometimes actual precipitating events in cerebral ischemia. From available studies, the incidence of precipitation is not clear. To determine this, we undertook a comprehensive investigation of all patients with ischemic brain disease for a one-year period. Results reveal that brain ischemia is more commonly precipitated by systemic illness than usually supposed, particularly transient ischemic attacks of the vertebrobasilar circulation and completed infarcts in the carotid distribution. Cardiac disorders outnumber all other precipitating events. As they are more amenable to therapy than atherosclerosis, a diligent search for such precipitating events is warranted in patients with ischemic symptoms.

Aged↗
PubMed1975

Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines.

Three Abelson virus-transformed lymphoma cell lines were established in tissue culture and the immunoglobulin biosynthesis by these cell lines was studied. Two of the cell lines (ABLS-1 and ABLS-5) were found to synthesize monomeric IgM molecules which were deposited in the cell membrane, probably to serve as an antigen receptor. The third cell line (ABLS-8) was found to synthesize membrane-associated IgM as well as cellular IgG molecules. In addition, these cell lines were found to synthesize a protein of 35,000 molecular weight which is also membrane-associated and which has the capability to bind the immunoglobulin (MAID). It is speculated that this protein might play a role in adapting the receptor immunoglobulin molecule to the hydrophobic environment of the cell membrane. The kinetics of amino acid incorporation into immunoglobulins by these cell lines show that they produce immunoglobulins at a rate which is two orders of magnitude smaller than plasmacytoma cells (MOPC 104E). These results suggest that Abelson virus transforms thymus-independent lymphocytes in various stages of maturation and these lymphocytes might be of B cell origin. The T lymphoma (P1798) used as a control cell line was found occasionally to produce minute amounts of immunoglobulin.

Cell Line↗
PubMed1975

A human lymphoid cell line secreting immunoglobulin G and retaining immunoglobulin M in the plasma membrane.

A selected clone, LA 85.2, of a human lymphoid cell line produces, mu gamma, and light chains. The cells secrete IgG but not IgM. Assembly of mu chains and light chains produces 8S IgM which is retained in the plasma membrane. IgM is produced at a slow rate and in lesser amounts than IgG. LA 85.2 cells produce a plasma membrane protein which can bind to antibody-antigen precipitates. It is suggested that this protein plays a role in holding the surface IgM in the plasma membrane.

Antigen-Antibody Complex↗