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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 217 records · Page 12Linked to original sources

Selective expression of class-II MHC antigens during hemopoietic differentiation.

Human multipotential or "mixed" bone marrow colony-forming cells and lineage-restricted colony-forming progenitors have been analyzed by cell sorting (FACS) using a series of monoclonal antibodies. The latter all react with monomorphic class-II MHC glycoprotein determinants but differ in their reactivity or cross-reactivity with products of different loci, i.e., SB (DP), DC (DQ), DR. The results confirm that very few progenitor cells detectably express DC. Anti-DR monoclonals varied in their reactivity with progenitor cells. The majority of progenitors in all lineage categories express determinants that are shared or cross-reactive between DR and SB while fewer progenitors can be shown to bind antibodies specific for DR or SB.

Antibodies, Monoclonal↗

Signals involved in T cell activation. I. Phorbol esters enhance responsiveness but cannot replace intact accessory cells in the induction of mitogen-stimulated T cell proliferation.

The role of accessory cells (AC) in the initiation of mitogen-induced T cell proliferation was examined by comparing the effect of intact macrophages (M phi) with that of 4-beta-phorbol 12-myristate 13-acetate (PMA). In high-density cultures, purified guinea pig T cells failed to proliferate in response to stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or PMA alone. The addition of M phi to PHA or Con A but not PMA-stimulated cultures restored T cell proliferation. The addition of PMA to high-density T cell cultures stimulated with PHA or Con A also permitted [3H]thymidine incorporation, but was less effective than intact M phi in this regard. This action of PMA was dependent on the small number of AC contaminating the T cell cultures as evidenced by the finding that PMA could not support mitogen responsiveness of T cells that had been depleted of Ia-bearing cells by planning, even when these cells were cultured at high density. When PMA was added to T cell cultures supported by optimal numbers of M phi, catalase-reversible suppression of responses was noted. Even in cultures containing catalase, PMA failed to enhance responsiveness above that supported by optimal numbers of M phi. A low-density culture system was used to examine in greater detail the possibility that PMA could completely substitute for M phi in promoting T cells activation. In low-density cultures, mitogen-induced T cell proliferation required intact M phi. PMA could not support responses even in cultures supplemented with interleukin 1-containing M phi supernatants or purified interleukin 2 alone or in combination. Similar results were found in high-density cultures of T cells depleted of Ia-bearing cells. These results support a model of T cell activation in which AC play at least two distinct roles. The initiation of the response requires a signal conveyed by an intact M phi, which cannot be provided by either a M phi supernatant factor or PMA. The response can be amplified by additional M phi or M phi supernatant factors. PMA can substitute for M phi in this regard and can provide the signal necessary for amplification of T cell proliferation supported by small numbers of intact AC.

Adjuvants, Immunologic↗

Data acquisition using a scintillation detector interfaced to a personal microcomputer.

A method is described for interfacing a cadmium telluride semiconductor nonimaging detector to a personal microcomputer in order to store and display nuclear medicine data. There was virtual identity between the count rates stored in the computer and those recorded from the detector's display, demonstrating that the computer accurately acquired data from the probe without erroneous loss or addition of data. Interfacing a nonimaging detector to a microcomputer may provide an extremely versatile method of acquiring, storing, and displaying nuclear medicine data.

Computers↗

Psychoeducational and impulsivity correlates of platelet MAO in normal children.

The authors examined the relationship between the activity of platelet monoamine oxidase (MAO) and a variety of psychoeducational measures, as well as the scores on the Matching Familiar Figures Test (MFF), a psychological test of reflection-impulsivity, in 21 normal children (12 boys, 9 girls) who were admitted to a clinical research center and placed on a low monoamine diet. The children were divided into three equal groups (n = 7) based on their values of platelet MAO. There were no significant differences among the three groups in the psychoeducational measures. However, the high and low MAO groups made significantly more errors and had shorter latency periods on the MFF than the middle MAO group. These findings suggest that normal children with platelet MAO activity values in the high and low ends of the MAO distribution are more impulsive than the children with platelet MAO values in the middle range on the MFF Test of Impulsivity. The findings further suggest that there is no relationship between platelet MAO levels and intellectual abilities or scholastic achievement in normal children.

Achievement↗

Mixed beam radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study.

Three hundred and twenty-two patients with inoperable squamous cell carcinomas of the head and neck were entered on a randomized study comparing "mixed beam" radiation therapy with photon radiation therapy. Patients with histologically proven tumors of T-stage T2, T3, or T4 and any N-stage originating in the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were eligible. One hundred forty-five patients were randomized to photon treatment and 177 were randomized to mixed beam treatment. No significant differences could be demonstrated between the experimental and control groups for primary tumor control or overall survival, although there was an advantage for mixed beam treatment over photon treatment for patients with metastatic cervical adenopathy (69 vs. 55% complete response rate in the nodes, p = .024). It is concluded that mixed beam radiation therapy does not offer a significant advantage over photon radiation therapy for patients with advanced squamous cell carcinomas of the head and neck.

Aged↗

Postnatal development of the bronchiolar Clara cell in rats.

We studied aspects of perinatal rat bronchiolar Clara cell development. We found that the volume density (Vv) of glycogen areas decreased 10-fold between postnatal days 1 and 2 and that the Vv of secretory granules, rough endoplasmic reticulum (RER), and mitochondria increased markedly during the 1st postnatal wk. Compared with pups of dams allowed food ad libitum during gestation, pups from dams underfed during gestation had a higher Vv of glycogen areas for the first 2 postnatal days but a lower Vv of secretory granules and RER for the time studied (to age 7 days). Glucagon injected, in utero, into fetal rats at 21.5 days of gestation resulted in a 40% decrease in the Vv of the glycogen areas within 4 h. We conclude that 1) bronchiolar Clara cells are immature at birth and undergo marked early postnatal maturation, 2) prenatal events (maternal undernutrition) affect postnatal maturation of the Clara cells, and 3) exogenous glucagon leads to glycogen depletion in Clara cells of fetal rats of 21.5 days gestation.

Animals↗

Decarboxylation of glycine by serine hydroxymethyltransferase in the presence of lipoic acid.

Serine hydroxymethyltransferase and the glycine cleavage system are both present in liver mitochondria and both bind glycine to form a pyridoxal 5'-phosphate carbanionic quinoid species. Lipoic acid has been shown to have the ability to intercept the carbanionic intermediate formed from the binary complex of serine hydroxymethyltransferase and glycine and form an intermediate adduct which is ultimately processed to yield CO2 and a methylamine adduct. Kinetic studies have shown that the lipoic acid-dependent decarboxylation of glycine catalyzed by serine hydroxymethyltransferase proceeds through a sequential mechanism. This lipoic acid-dependent decarboxylation catalyzed by serine hydroxymethyltransferase is similar to the initial reaction of the glycine cleavage system and to the lipoic acid-dependent decarboxylation of glycine by the P-protein alone suggesting that both enzymes could serve in lieu of each other.

Animals↗

2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s: novel antihypertensive agents.

A series of 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine]s (IV) and 2,3-dihydro-3-(1-pyrryl)spiro[benzofuran-2,3'-pyrrolidine]s (V) was synthesized and evaluated for cardiovascular activity. The majority of the compounds displayed good antihypertensive activity in the spontaneous hypertensive rat model at 50 mg/kg po. Compounds 5 (2,3-dihydro-1'-methyl-3-(1-pyrryl)spiro[benzofuran-2,4'-piperidine] ) and 12a (2,3-dihydro-1'-ethyl-3-(1-pyrryl)-spiro[benzofuran-2,4'-piperidine] ) were selected for a more detailed cardiovascular evaluation in the renal hypertensive rat and for standard cardiovascular challenges in anesthetized dogs and the sinoaortic-deafferented dog.

Animals↗

Variegate porphyria and heavy metal poisoning from ingestion of "moonshine".

A patient with cavitary tuberculosis, hepatic cirrhosis, bullous skin lesions over sun-exposed surfaces, disorientation, and a chronic, as well as recent, history of illicit alcohol consumption was found to have acute variegate porphyria by characteristic fecal and urinary porphyrin studies. Elevated levels of lead and arsenic were found in serum and urine without evidence of heavy metal storage in hair and liver. We suspect that the variegate porphyria was precipitated by the ingestion of heavy metals contained in illicit alcohol. In a patient with disorientation, bullous skin lesions, and a history of illicit alcohol ingestion, one must consider heavy metal intoxication and secondary porphyrin abnormalities.

Aged↗

Selective pigment medium for Streptococcus agalactiae.

Increased awareness of the importance of Streptococcus agalactiae (Group B streptococcus) in neonatal morbidity and mortality has demonstrated the need for a selective and differential primary plating medium. In this report we describe a selective pigment medium containing colistin and nalidixic acid that allows presumptive identification of S. agalactiae from the primary plate, even when specimens are polymicrobic. A preliminary study compared the value of three media for pigment production by 137 known S. agalactiae strains. This was followed by a clinical laboratory trial using the best of these pigment media at an obstetric hospital in which 581 specimens from neonates, female reproductive tracts, and urinary tracts were screened. Subsequent to the clinical laboratory trial, an epidemiological investigation using the selective pigment medium was conducted on a mother/infant population. Of the 1,331 specimens screened for S. agalactiae, 75 (5.6%) were positive on 5% sheep blood agar and 79 (5.9%) were positive on the selective pigment medium.

Adult↗

The influence of immunoglobulin (IgG) on the assembly of fibrin gels.

The presence of immunoglobulin is shown to alter the network structure of gels formed from purified fibrinogen. Turbidity measurements were used to calculate the effect of increasing concentrations of immunoglobulin on the mass-length ratio of fibrin fibers composing the gels. Normal pooled, human IgG was found to reduce the mass-length ratio of fibrin fibers composing the gel from 7 X 10(12) daltons/cm with no immunoglobulin to 1 X 10(12) in the presence of 40 mg/ml. Monoclonal IgGk was found to be more effective in the reduction of the mass-length ratio than normal IgG. This observation indicates that the immunoglobulin must decrease lateral association of fibrin protofibrils. As the mass-length ratio decreased, the rigidity of the gels increased as the immunoglobulin concentration was elevated (1.2 dynes/cm2 with no immunoglobulin to 2.9 at 15 mg/ml). Since the fibrin fiber diameters were decreased, the number of interfiber crosslinks must have been increased to explain the increase in rigidity. Antifibrinogen, antifibrin intermediate, and antithrombin antibody activity of the immunoglobulins were proved unlikely.

Antibodies, Monoclonal↗

[(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids. A new diuretic series.

A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best diuretic activity (13i, 13q, and 13ff) were substituted with a 2-fluorophenyl group at the 3 position and chlorine or bromine at the 7 position. Compound 13ff, [(7-bromo-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid (HP 522), was found to be moderately uricosuric in chimpanzees and was selected for further development.

Animals↗

Altered regulation of isoleucine-valine biosynthesis in a hisW mutant of Salmonella typhimurium.

Control of isoleucine-valine biosynthesis was examined in the cold-sensitive hisW3333 mutant strain of Salmonella typhimurium. During growth at the permissive temperature (37 degrees C), the isoleucine-valine (ilv) biosynthetic enzyme levels of the hisW mutant were two- to fourfold below these levels in an isogenic hisW+ strain. Upon a reduction in growth temperature to partially permissive (30 degrees C), the synthesis of these enzymes in the hisW mutant was further reduced. However, synthesis of the ilv enzymes was responsive to the repression signal(s) caused by the addition of excess amounts of isoleucine, valine, and leucine to the hisW mutants. Such a "super-repressed" phenotype as that observed in this hisW mutant is similar to that previously shown for the hisU1820 mutant, but was different from the regulatory response of the hisT1504 mutant strain. Moreover, by the use of growth-rate-limiting amounts of the branched-chain amino acids, it was shown that this hisW mutant generally did not increase the synthesis of the ilv enzymes as did the hisW+ strain. Overall, these results are in agreement with the hypothesis that the hisW mutant is less responsive to ilv specific attenuation control than is the hisW+ strain and suggest that this limited regulatory response is due to an alteration in the amount or structure of an element essential to attenuation control of the ilv operons.

Acetolactate Synthase↗