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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 253 records · Page 14Linked to original sources
PubMed1991

Cancer control and the older person. Prevention and detection in older persons.

Older persons are appropriate targets for a range of prevention and early detection interventions, however, greater emphasis should be given to structuring the delivery of prevention and detection services to the special needs of this population. This may require research and program development to reach older persons in the most effective and cost-effective manner. The American Cancer Society and other program efforts must accommodate the heterogeneity and special needs of segments of the older population. Racial and cultural minorities, impoverished persons, the cognitively impaired, and the physically impaired are four groups requiring special attention. Early detection guidelines specific to older persons should be developed.

Aged↗
PubMed1991

Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites.

The antitumor effects of two anti-CD22 ricin A chain-containing immunotoxin (IT) constructs were compared in mice with severe combined immunodeficiency disease with human Daudi cell tumors (SCID-Daudi mice). SCID-Daudi mice develop disseminated lymphoma that clinically resembles African Burkitt's lymphoma, i.e., extranodal disease including infiltration of the vertebral column and spinal canal. In the absence of treatment, the mean survival time of SCID-Daudi mice was 45.9 +/- 4.3 days. The mice was given injections of a dose of IT equal to 40% of the 50% lethal dose. The ITs consisted of either IgG or Fab' fragments of mouse anti-CD22 antibody coupled to deglycosylated ricin A chain (dgA). Both ITs were potent and specific and inhibited protein synthesis in Daudi cells in vitro by 50% at concentrations of 1.2 x 10(-12) (IgG-dgA) and 1.3 x 10(-11) M (Fab'-dgA). When administered to mice beginning 1 day after inoculation with tumor cells, both ITs extended the mean survival time, to 87.2 +/- 18.9 days (IgG-dgA) or 57.9 +/- 3.8 days (Fab'-dgA). The latter represented the killing of 2 logs of Daudi cells, and the former 4 logs. IgG antibody alone killed 1 log of tumor cells. The IgG-dgA had an antitumor effect even when administered 20-23 days after tumor inoculation. Gross and histological examinations of IT-treated tumor-bearing mice showed a marked decrease in the number and size of neoplastic foci in both lymphoid organs and extranodal sites.

Animals↗
PubMed1991

Decreased catalytic subunit mRNA levels and altered catalytic subunit mRNA structure in a cAMP-resistant Chinese hamster ovary cell line.

The mechanisms responsible for decreased levels of cAMP-dependent protein kinase activity in a mutant Chinese hamster ovary cell line have been examined. The cAMP-resistant Chinese hamster ovary 10260 cell line was found to possess only 20% of the cAMP-dependent protein kinase activity found in wild-type cells. The presence of decreased concentrations of the catalytic subunit in these cells was confirmed through binding studies using a radiolabeled, heat-stable inhibitor of the kinase. Cloned Chinese hamster ovary catalytic subunit cDNAs were isolated, characterized, and used as hybridization probes to examine the relative concentrations of catalytic subunit mRNAs in the wild-type and 10260 cell lines. A 40-50% decrease in the concentration of the mRNA for the C alpha isozyme of the catalytic subunit was observed in 10260 cells, as compared with wild-type. This decrease in catalytic subunit mRNA concentration probably accounts for a portion of the decreased kinase activity in the mutant cells. Further analysis of C alpha mRNA by polymerase chain reaction confirmed the decreased expression of C alpha mRNA in 10260 cells and further demonstrated the presence of two different species of C alpha mRNA in the 10260 cells. One species of C alpha cDNAs was indistinguishable from the wild-type cDNA, but the other species was shorter. Nucleotide sequence analysis of the amplified cDNAs led to the identification of a 191-base pair deletion in the shorter cDNA. Gene transfer studies using wild-type and 10260 C alpha cDNAs demonstrated that the longer cDNA from the 10260 cells produced wild-type activity, but the shorter cDNA was inactive. These studies suggest that at least two alterations in gene expression are responsible for decreased cAMP-dependent protein kinase activity in the 10260 cell line. One alteration results in an approximately 2-fold decrease in the concentrations of C alpha mRNA in the cells. The other change produces two species of C alpha mRNA; one of the C alpha mRNAs does not encode an active kinase.

Amino Acid Sequence↗
PubMed1991

Operation, formulary decision-making activities of a P & T Committee in a managed care setting.

Managing drug benefits in a Health Maintenance Organization (HMO) is perhaps best accomplished through a formulary, as demonstrated by Kaiser Permanente of Colorado. According to Dr. Jim Adams and Ms. Jackie Richardson, the Chairman and Secretary, respectively, of Kaiser Permanente's P & T Committee, since the advent of their formulary only a few years ago, the cost of drugs has been kept well under control, without jeopardizing the quality of care. Both physician and patient education are critical to the success of a formulary in a managed care system--both monumental tasks for Kaiser Permanente of Colorado considering that prescribers exceed 300 and the number of patients they treat approaches 250,000. What is clear in this exclusive Hospital Formulary interview is that HMOs--long recognized for their ability to control costs--can also provide quality health care for patients who use their facilities.

Colorado↗
PubMed1991

Use of red blood cells older than five days for neonatal transfusion.

Sick neonates often require periodic small volume transfusions (10 mL/kg) to replace blood drawn for laboratory monitoring during their hospital stay. We use red blood cells (RBCs), stored as CPDA-1 whole blood, up to their expiration date, and are unaware of any clinical problems with this practice. We proceeded to confirm our clinical impression by reviewing the hospital records of 22 transfused neonates who received a median of 2.5 RBC transfusions (range 1 to 11) with a volume of 16 mL (range 5 to 38) each, and total volume of 60 mL (range 16 to 152). The RBCs were stored a median of 7 days (range 2 to 27). Following transfusion, there was an increase (P less than .05) in hemoglobin (mean 2.8 +/- 1.6 gm/dL [SD]) and hematocrit (9.0% +/- 4.7%). The bilirubin also rose (0.6 +/- 1.5 mg/dL, P less than .05), but this was not considered clinically significant. No significant change occurred in pH or bicarbonate. Paradoxically, RBCs over 10 days of age resulted in a fall in potassium (-0.9 +/- 0.8 mEq/L, P less than .01), but not below 3.4 mEq/L. We could find no evidence by clinical observation or laboratory indexes that small volume transfusion of RBCs more than 5 days old was deleterious to the newborns studied. By using RBCs up to their expiration date, the number of donor exposures and the potential risk of transfusion-transmitted diseases can be decreased.

Blood Preservation↗
PubMed1990

Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice.

A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B-17 SCID. Twenty-eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v. inoculation, tumors grew in the lungs, kidneys, ovaries and adipose tissue, and microscopic tumor infiltrates were observed in the spleen, bone marrow, spinal column and femur, whereas after i.p. injection, the tumors were localized in the abdomen, liver, spleen, ovaries and muscular tunics of the gut, but did not disseminate into the lung or bone marrow. The growth pattern and phenotype of the Daudi cells were similar whether the inoculated tumor cells were derived from the in vitro cell line or from in vivo passaged tumors. The survival time of the tumor-bearing animals was dependent on the dose of i.v.-administered Daudi cells; as few as 100 cells caused death. All mice injected i.v. showed paresis or paralysis of the hind legs just prior to death. This was associated with the presence of neoplastic nodules within the spinal canal. Two surface antigens on Daudi cells (CD19 and CD22) were stably expressed in all the neoplastic lesions. Radiolabelled anti-CD22 antibodies localized in organs infiltrated with tumor, but did not penetrate primary s.c. tumors. This model of disseminated vs. solid tumor should prove useful for evaluating the efficacy of different types and doses of therapeutic antibodies, immunoconjugates and immunotoxins prepared from anti-human B-cell antibodies.

Animals↗
PubMed1990

Biochemical and genetic analysis of the biosynthesis, sorting, and secretion of Dictyostelium lysosomal enzymes.

Dictyostelium discoideum is a useful system to study the biosynthesis of lysosomal enzymes because of the relative ease with which it can be manipulated genetically and biochemically. Previous studies have revealed that lysosomal enzymes are synthesized in vegetatively growing amoebae as glycosylated precursor polypeptides that are phosphorylated and sulfated on their N-linked oligosaccharide side-chains upon arrival in the Golgi complex. The precursor polypeptides are membrane associated until they are proteolytically processed and deposited as soluble mature enzymes in lysosomes. In this paper we review biochemical experiments designed to determine the roles of post-translational modification, acidic pH compartments, and proteolytic processing in the transport and sorting of lysosomal enzymes. We also describe molecular genetic approaches that are being employed to study the biosynthesis of these enzymes. Mutants altered in the sorting and secretion of lysosomal enzymes are being analyzed biochemically, and we describe recent efforts to clone the genes coding for three lysosomal enzymes in order to better understand the molecular mechanisms involved in the targeting of these enzymes.

Acid Phosphatase↗
PubMed1990

Significance of fever in hospital employees.

Hospital employees are exposed to a variety of occupationally related hazards that can be categorized as infectious or noninfectious. Lost work time often results from these problems. Infection control practitioners receive many telephone calls of inquiry about these employees in terms of their transmissible infections. Little has been written concerning fever in the employee health setting. To determine the frequency of febrile illness in hospital employees, we conducted a prospective study of the employee health service from January to December 1987. Winthrop-University Hospital is a 533-bed community teaching hospital with approximately 2400 employees. During 1987, 2974 visits were made to the employee health service. Of these, 879 (30%) were for occupationally related illness or injury. Oral temperatures of greater than or equal to 100 degrees F were noted in 25 (2.8%) of the 879 visits. Fever occurred predominantly in employees with infections. Upper respiratory tract infection accounted for 268 of 544 (49%) visits for infection. In addition, 11 of 22 (50%) febrile episodes were related to upper respiratory tract infections. A total of 963 work days were lost because of illness or injury. Of these, 743 (77%) were related to an infectious illness; 67 sick days (7%) were attributed to infections with a febrile response. We conclude that fever is uncommon in our employee health care population and that upper respiratory tract infections were the single most common cause of fever. When an employee had a febrile illness, the lost work time was 9% of the total time loss because of infection.

Fever↗
PubMed1990

Abnormalities of carbohydrate metabolism and of OCT gene function in the Rett syndrome.

The pathogenetic basis of the Rett syndrome (RS) is unknown: an X-linked dominant, male-lethal gene defect is thought likely. We present a girl with RS who has defects both of the urea cycle and of carbohydrate metabolism resulting in fasting hypoglycaemia, post-prandial hyperlactataemia and excess urinary orotic acid excretion after alanine load. Her sister has a similar clinical picture, but less marked metabolic anomalies. The mother of these sisters has abnormal urinary orotic acid excretion; she transmitted opposite ornithine carbomoyltransferase (OCT) alleles to the two girls. Another girl with RS has similar metabolic responses to fasting and to carbohydrate load. We conclude that RS may be an aetiologically homogeneous condition, but that it includes a variable pattern of metabolic anomalies, and that the gene defect is distinct from the OCT locus.

Adolescent↗
PubMed1990

Role of arginine 180 and glutamic acid 177 of ricin toxin A chain in enzymatic inactivation of ribosomes.

The gene for ricin toxin A chain was modified by site-specific mutagenesis to change arginine 180 to alanine, glutamine, methionine, lysine, or histidine. Separately, glutamic acid 177 was changed to alanine and glutamic acid 208 was changed to aspartic acid. Both the wild-type and mutant proteins were expressed in Escherichia coli and, when soluble, purified and tested quantitatively for enzyme activity. A positive charge at position 180 was found necessary for solubility of the protein and for enzyme activity. Similarly, a negative charge with a proper geometry in the vicinity of position 177 was critical for ricin toxin A chain catalysis. When glutamic acid 177 was converted to alanine, nearby glutamic acid 208 could largely substitute for it. This observation provided valuable structural information concerning the nature of second-site mutations.

Animals↗
PubMed1990

Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures.

Chorioretinal neovascular membranes are a recognised but rare cause of late visual loss in eyes suffering contusional injuries. A series of eight cases is presented all with indirect choroidal ruptures involving the perifoveal region. Two main patterns of 'at risk' rupture were noted: a temporally situated rupture passing almost directly through the fovea, and a rupture which curves inferior or superior to the optic disc stopping just short of the fovea. In six of eight cases there was only a partial thickness rupture of the choroid. These neovascular membranes may present at any time after the original injury, either early (within six months of the injury), which could be related to persistence of the normal reparative neovascular response, or late (at least one year after the injury), which are more likely to have resulted from a secondary breakdown of the outer blood-retina barrier.

Adolescent↗