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Biomedical subjects

D Patterson

Publications and source records attributed to D Patterson.

At least 199 records · Page 11Linked to original sources
PubMed1985

5-Amino-4-imidazolecarboxamide riboside (Z-riboside) metabolism in eukaryotic cells.

Metabolites of 5-amino-4-imidazolecarboxamide riboside (Z-riboside) have potential roles in the regulation of cellular metabolism and as pharmacological agents in several pathological situations. Before studying Z-riboside metabolism it was necessary to develop methods for identifying and quantitating 5(4)-amino-4(5)-imidazolecarboxamide metabolites. These studies utilized Chinese hamster ovary fibroblast auxotrophic mutants to identify and isolate compounds relevant to Z-riboside metabolism by a combination of high performance liquid chromatographic procedures. In order to study Z-riboside metabolism wild-type and mutant cells were cultured in Z-riboside. This ribosyl precursor to a purine de novo intermediate does not undergo any detectable phosphorolysis but rather is phosphorylated by adenosine kinase in an unregulated manner. This results in the intracellular accumulation of 5-amino-4-imidazolecarboxamide ribotide (ZMP), the levels of which control flow from Z-riboside to the following metabolites: 1) IMP and other purine nucleotides, 2) 5-amino-4-imidazole-N-succinocarboxamide ribotide (sZMP), and 3) 5-amino-4-imidazolecarboxamide riboside 5'-triphosphate (ZTP). At low ZMP concentrations, the predominant metabolic fate is IMP. Initially, IMP enters the adenylate and guanylate pools, but subsequently is hydrolyzed to inosine and this phosphorolyzed to hypoxanthine. At intermediate ZMP concentrations there is net retrograde flux through the bifunctional enzyme adenylosuccinate AMP lyase resulting in sZMP synthesis and antegrade flux leads to the accumulation of adenylosuccinate. At high ZMP concentrations, ZTP accumulates. In addition to these effects on purine metabolism, pyrimidine nucleotide pools are depleted when ZMP accumulates. These results are discussed in relation to the regulation of purine nucleotide synthesis and the use of Z-riboside as a pharmacological intervention in pathophysiological situations.

Adenosine Monophosphate↗
PubMed1985

Identification and localization of DNA alteration in Chinese hamster ovary cell mutants (Urd-) defective in the first three enzymes of de novo pyrimidine synthesis.

In animals, the first three enzymatic steps of de novo pyrimidine synthesis, carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase, comprise the multifunctional protein known as the CAD protein. Mutants of Chinese hamster ovary cells (CHO-K1, pro-) deficient in CAD protein activities require uridine for growth and are designated Urd-A mutants. To examine further the nature of the genetic alterations in Urd-A mutants and revertants, we have performed a detailed Southern blot hybridization analysis of DNA from wild-type, Urd-A, and revertant cells using as hybridization probes cDNAs complementary to CAD mRNA isolated from Syrian hamster. This has allowed us to identify an apparent alteration in the CAD gene in DNA from Urd-A cells. This alteration is in a region of the gene which appears to correspond to the region of the protein which is hypersensitive to proteases and which seems to be altered in the mutants. Only one of the two CAD alleles present appears to be altered in this way. Study of certain revertants of Urd-A strongly suggests that in some cases reversion has occurred by amplification of the mutant CAD allele.

Alleles↗
PubMed1985

Isolation and analysis of the 21q+ chromosome in the acute myelogenous leukemia 8;21 translocation: evidence that c-mos is not translocated.

Acute myelogenous leukemia (AML), subgroup M2, is associated with a nonrandom chromosomal translocation, t(8;21)(q22,q22). The oncogene c-mos also has been localized to the q22 band on chromosome 8. There is also evidence that genes on chromosome 21 may be important in the development of leukemia. To determine whether the c-mos oncogene has been translocated in AML-M2 with this translocation and to isolate DNA sequences and genes from these two chromosomes that may be important in malignancy, we constructed somatic cell hybrids between a Chinese hamster ovary cell (CHO) mutant defective in glycine metabolism and myeloblasts with an 8;21 translocation from a patient with AML. We isolated the 21q+ chromosome of this translocation in a somatic cell hybrid and showed that the c-mos oncogene had not been translocated to chromosome 21, ruling out the possibility that translocation of c-mos to chromosome 21 is necessary for development of AML-M2. In addition, there was no detectable rearrangement of the c-mos locus within a 12.4-kilobase region surrounding the gene, indicating that rearrangement of the coding region of the gene itself or alteration of proximal 5' or 3' flanking sequences is not involved. We used this hybrid to determine whether specific DNA sequences and biochemical markers from chromosomes 8 and 21 had been translocated in this case.

Animals↗
PubMed1985

Translocation of c-myc in the hereditary renal cell carcinoma associated with a t(3;8)(p14.2;q24.13) chromosomal translocation.

A translocation between chromosomes 3 and 8, t(3;8)(p14.2;q24.13), has been reported in a family with hereditary renal cell carcinoma. Using somatic cell hybrids, we have isolated, separately, both derivative chromosomes. We find that the c-myc oncogene (8q24.1) has been translocated to the derivative 3 [der(3)]. We have not detected a rearrangement within an approximately equal to 21-kilobase region around the c-myc gene using restriction enzyme digestion and Southern blot hybridization analysis. The translocated c-myc gene should provide a probe to the chromosome 3p14 region, which appears to be important not only in renal cell carcinoma but also in small cell carcinoma of the lung. These hybrids have also been useful for the regional mapping of the Chinese hamster ovary cell Gly-B defect to 8q22.1----q24.13 and support the regional assignment of acylase I to 3p21.

Animals↗
PubMed1985

Angina.

Ideas about the aetiology and pathology of angina have changed considerably. The "dynamic" nature of coronary arteries is now well recognized. Treatment is beginning to respond to these developments. In particular, the old "medical" versus "surgical" argument is inappropriate--treatment should be tailored to the patient's individual need.

Adrenergic beta-Antagonists↗
PubMed1985

Children's knowledge of diabetes and implications for self-care.

Fifty-seven children with diabetes (mean age = 12.0 years) were given a forced choice questionnaire to assess their knowledge of the disorder. Parents of 81% of these children completed a second questionnaire to determine how responsible children were for their own self-care. Children were also observed drawing up their own insulin. The data suggest that children who were responsible for their own injections were adequately informed about this aspect of treatment (chi 2 = 9.98, df = 1, p less than 0.05) but those who were felt to be responsible for their own diets were not well informed in this regard (chi 2 = 2.08 N.S.) The data are discussed in terms of the implications for teaching children about diabetes and the insight they give into the effects of diabetes on family life.

Adolescent↗
PubMed1985

[Colony-stimulating activity of bone marrow preparations in patients with different pathology of the blood].

The authors offer a method for cultivating trepanobiopsies in the agar drop-liquid medium system to measure the intramedullary colony-stimulating activity (CSA) in patients with different pathological conditions of the blood system. In patients with chronic idiopathic neutropenia and aplastic anemia, the CSA of the whole bone marrow tissue ranges within normal. In patients with recurrent acute myelo- and leukoblastic leukemias, the CSA of trepanobiopsies is lowered. During a remission, in these patients and in those with hemopoietic dysplasia the CSA of the whole bone marrow tissue ranges within normal. There is a positive correlation between the CSA of trepanobiopsies and the number of mature granulocytes in the peripheral blood of patients with acute myeloleukemia and lymphoblastic leukemias and a negative correlation between the CSA and the number of blast cells in the blood and bone marrow of patients with acute lymphoblastic leukemia. It has been thus shown that intramedullary level of the CSA plays a great part in regulation of granulomonocytopoiesis in health and different pathological conditions. It is assumed that stromal elements of the bone marrow may release a factor that is triggered by the colony-stimulating factor or by this factor-synthesizing cells.

Agar↗
PubMed1985

Binding of Al by protein in plasma of patients on maintenance hemodialysis.

Gel filtration of plasma from hemodialysis patients, with use of reagents and apparatus with carefully minimized background Al concentrations, reproducibly showed a single peak for Al, corresponding exactly to the elution position of transferrin. The Al/transferrin molar ratio in adjacent fractions was constant (mean 0.126, SE 0.006) in replicate experiments. In contrast, the association of Al with albumin varied. Using both equilibrium dialysis and gel-filtration techniques, in the presence and absence of calcium or phosphate, we could demonstrate no significant binding of Al by human albumin at Al concentrations of 1 to 12 mumol/L. We saw no Al peak in pooled, concentrated, low-molecular-mass fractions of plasma gel-filtered on Sephadex G-50. Evidently, transferrin is the sole Al-binding protein in plasma of hemodialysis patients.

Aluminum↗
PubMed1984

Children's perceptions of hospital: a preliminary study.

Three groups of children (5-6, 7-8 and 9-10 years) were interviewed about their knowledge and attitudes towards hospitals. Children were asked what they thought happened in hospitals, why people were admitted and how they became better. They were also asked the worst and best things about being in hospital. The responses of the 5-6 year old group were very inadequate, but children's perceptions of hospital varied as a function of age. The results have implications both for preparing children prior to hospitalization and dealing with emergency admissions.

Age Factors↗
PubMed1984

Factors affecting the nurse as a teacher and practicer of breast self-examination.

The purpose of this study was to compare the knowledge, attitudes, confidence and practice of breast self-examination of a group of hospital-employed nurses and non-nurses, in an attempt to understand the factors which influence why nurses do not teach or practice breast self-examination more significantly. A 41-item questionnaire administered to 380 female hospital employees compared data on demographics, risk factors, practice, knowledge, perceived susceptibility and reasons for and against practice. The findings show significant differences in knowledge levels and confidence between the nurse and non-nurse group. The differences between the two groups in frequency of practice, however, are extremely small. The significance of these findings to nursing education is discussed.

Attitude to Health↗
PubMed1984

Diabetes and developing knowledge of the body.

Fifty seven diabetic children were compared with healthy children for knowledge of their bodies and causes of diabetes. Diabetic children were more likely to include the pancreas and less likely to include the brain or stomach in drawing their bodies. The data have implications for understanding how illness affects psychological development.

Adolescent↗
PubMed1983

Resistance of Chinese hamster ovary cell chromatin to endonuclease digestion. I. Reversal by cAMP.

A portion of the DNA within intact nuclei of a spontaneously transformed Chinese hamster ovary cell line (CHO-Kl) is relatively resistant to digestion by pancreatic deoxyribonuclease, as compared to nuclei from primary cultures of Chinese hamster ovary fibroblasts. Treatment of CHO-Kl cells with derivatives of 3',5' cyclic AMP (cAMP) under conditions which effect the reverse transformation (RT) of these cells, results in restoration of the increased sensitivity of their DNA to hydrolysis by pancreatic deoxyribonuclease, to the level characteristic of an untransformed, morphologically normal Chinese hamster fibroblast cell line. Dibutyryl (db-)cAMP and 8-bromo-cAMP (Br-cAMP) yielded similar results. The cAMP derivatives employed had no effect on the normal fibroblasts.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Isolation and characterization of a Chinese hamster ovary cell mutant which accumulates UDP glucuronic acid and requires uridine for growth.

The isolation and characterization of a new pyrimidine requiring mutant of Chinese hamster ovary cells (CHO-Kl, pro-) is described. This mutant (P192) shows an absolute requirement for uridine for growth but is fully capable of pyrimidine nucleotide synthesis. P192 cells accumulate exceedingly large amounts of a compound identified by a variety of chromatographic, chemical, and labelling criteria as UDP glucuronic acid (UDPglcUA). This compound comprises approximately 60% of the acid-soluble nucleotides of P192 cells. Possible genetic mechanisms leading to the phenotype of P192 are examined, and the role of UDPglcUA in cellular metabolism is discussed.

Animals↗
PubMed1983

Structural gene coding for multifunctional protein carrying orotate phosphoribosyltransferase and OMP decarboxylase activity is located on long arm of human chromosome 3.

In humans, deficiency in the last two enzymes of UMP biosynthesis, orotate phosphoribosyltransferase (OPRT) and OMP decarboxylase results in the inborn error of metabolism hereditary orotic aciduria, type 1. In this manuscript, we present immunologic, molecular, biochemical, and genetic evidence that the gene coding for this set of enzymatic activities is located on the long arm of human chromosome 3. The evidence presented here is consistent with both these activities being carried on the same multifunctional protein in mammalian cells. These studies allow further genetic analysis of human chromosome 3, confirming that human markers ACY-1, previously assigned to 3p21, and beta-gal, previously assigned by others to the region 3(p21-q21), must be in the region 3 (cen-p21) and confirming the regional assignment of a human DNA segment, D3S1, to 3q12. The significance of these studies to genetic analysis of genes on human chromosome 3, some of which appear to play a role in some forms of malignancy, is discussed.

Carboxy-Lyases↗
PubMed1983

Two-dimensional electrophoresis of peptides from human-CHO cell hybrids containing human chromosome 21.

Peptide expression influenced by human chromosome 21 was examined by comparing two-dimensional electrophoretograms of a human-hamster hybrid cell containing human chromosome 21 with its parent hamster cell and a revertant of the hybrid which had segregated the chromosome 21 genes for SOD-1, GARS, and a cytotoxic cell-surface antigen. Certain peptides were found in the hybrid but not in the hamster cell. Some, but not all, of these peptides segregated with markers for chromosome 21. Hamster peptides were also found which apparently were suppressed in the hybrid. Finally, one peptide was identified which was unique to the revertant cell. These findings may be of potential relevance to Down's syndrome.

Animals↗
PubMed1983

Cholestasis due to compression of the common bile duct by pancreatic pseudocysts.

We studied 10 patients with pancreatitis who had persistent cholestasis secondary to compression of the common bile duct by a pancreatic pseudocyst. Elevation of the serum bilirubin or alkaline phosphatase levels, or both, (sensitive indicators of cholestasis) was present in each of our patients. The diagnosis of a pancreatic pseudocyst is best made by CAT scan and ultrasonography. These techniques will delineate the small intrapancreatic pseudocyst that otherwise may be difficult to recognize on inspection at operation. Endoscopic retrograde cholangiography and pancreatography are desirable because they delineate the anatomic alterations of the pancreatic and common bile ducts and may contribute information pertaining to the possibility of common duct obstruction by pancreatic fibrosis. In our opinion, cholestasis secondary to bile duct compression by a pseudocyst is an indication for operation. Each of our 10 patients had drainage of their pseudocysts. Cystoduodenostomy, performed in seven patients, was the method most commonly used. If there is concern regarding the patency of the common duct after drainage of the cyst, intraoperative cholangiography should be performed. This was carried out in three patients. In each patient, the preoperative elevations of serum alkaline phosphatase and serum bilirubin levels returned to normal limits after operative decompression of a pancreatic pseudocyst alone without an accompanying or subsequent bilioenteric bypass being required.

Cholestasis↗