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Biomedical subjects

J Craig

Publications and source records attributed to J Craig.

At least 19 recordsLinked to original sources

Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophilia. Report of two cases.

Two cases are described with the rare combination of inv(16)(p13q22), strongly associated with acute myelomonocytic leukemia with eosinophilia, M4Eo, and the Philadelphia translocation, t(9;22)(q34;q11), hallmark of chronic myeloid leukemia (CML) and rarely found, (less than 1%), in acute nonlymphocytic leukemia. The patients were: case 1, a 9-year-old girl presenting with a white blood cell count (WBC) 42 x 10(9)/L with 32% blasts and bone marrow with blasts and eosinophil precursors consistent with M4Eo, and case 2, a 25-year-old man with WBC 34.7 x 10(9)/L with 13% blasts and bone marrow with features of M4Eo and basophilia. Both patients achieved remission but died following bone marrow transplantation in first remission (case 1) or in relapse (case 2). Cytogenetic findings were: case 1, at diagnosis, 46,XX,inv(16)(p13q22)(21)/46,XX,t(9;22) (q34;q11),inv(16)(8)/46,XX(10), and case 2, at diagnosis, 46,XY,t(9;22) (q34;q11),inv(16)(p13q22) (16) and in remission, 46,XY,t(9;22)(q34;q11) (1)/46,XY (24). Investigation of the breakpoint on 22 in case 1 with Southern blotting and the polymerase chain reaction demonstrated the presence of a p190 mRNA and a breakpoint typical of acute leukemia. Thus a diagnosis of M4Eo was supported by clinical and cytogenetic sequelae in each case; the Ph in case 1 was apparently secondary to inv(16), in case 2 the Ph probably preceded inv(16) in the etiology of the leukemia.

Adult

Soluble dietary fiber and cholesterol influence in vivo hepatic and intestinal cholesterol biosynthesis in rats.

Ninety-six male Sprague-Dawley rats were randomly assigned to eight dietary treatments. Rats were fed, with ad libitum access, diets containing 10% dietary fiber as cellulose (control), pectin, psyllium or oat bran with or without 0.3% added cholesterol for 3 wk. Among cholesterol-fed rats, liver total cholesterol was significantly lower in rats fed diets supplemented with either pectin or psyllium compared with those fed cellulose. In contrast, rats fed oat bran with cholesterol had significantly higher liver cholesterol concentrations compared with cellulose-fed animals. Liver total lipid concentrations were significantly lower in groups fed pectin and psyllium with or without dietary cholesterol compared with cellulose-fed controls. Pectin feeding with or without dietary cholesterol significantly lowered plasma total cholesterol compared with cellulose feeding. Oat bran had no effect on plasma total cholesterol compared with control diets. Hepatic sterol synthesis was significantly greater for animals fed soluble dietary fibers compared with those fed cellulose, but the effect on intestinal sterol synthesis was less pronounced.

Animals

Human immunodeficiency virus (HIV) seroprevalence surveys.

The seroprevalence surveys being conducted in the Kansas City area have to date tested 15,778 persons and resulted in 85 seropositive HIV tests. The sexually transmitted disease (STD) surveys and women's surveys fall in the lowest quartile of the combined national surveys. The drug treatment (IVDU) survey data were comparable to the median national seroprevalence of 3.8%. Seroprevalence rates in the STD surveys were 41 times that of women's surveys, and the IVDU surveys were 104 times that of the women's surveys. Based on three years of data from clinics with stable populations presenting for treatment, no trends in the demographics of those being found seropositive were identified to be statistically significant. This lack of trends has been presented as the normal findings of surveys nationally. The data does not show an acceleration of new infections based on seropositives being identified in the survey sites.

Community Health Centers

The postoperative cardiac infant: physiologic basis for neonatal nursing interventions.

The care of the postoperative cardiovascular neonate is complex and multifaceted. A comprehensive understanding of physiology, pathology, and appropriate interventions is necessary for a successful outcome. The neonatal nurse plays a pivotal role in the collaborative management of these neonates to support delivery of quality care.

Body Temperature Regulation

A phase I trial of taxol given by a 6-hour intravenous infusion.

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

Alkaloids

Human immunodeficiency virus (HIV) sero-prevalence in sexually transmitted disease clinic populations.

Two HIV sero-prevalence surveys conducted during 1989 in public sexually transmitted disease clinics in the Kansas City SMSA tested 1,561 males and 1.043 females. There were 23 sero-positive males; no sero-positive females. The rate for males using the Missouri clinic was nearly triple that of males using the Kansas clinic. Among males the sero-prevalence rate for white males was 8.4 times that for black males. Of the 14 HIV sero-positive males for whom risk factor information was available, 12 were gay or bisexual and two were heterosexual intravenous drug users.

Adult

Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus.

BACKGROUND AND METHODS: Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM: The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined. RESULTS: The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM: Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM: CONCLUSIONS: NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM:

Age Factors

The int-1 proto-oncogene is transcriptionally activated during neuroectodermal differentiation of P19 mouse embryonal carcinoma cells.

We have used the P19 line of mouse embryonal carcinoma (EC) cells to initiate studies on the putative role of the int-1 proto-oncogene during neuronal differentiation. P19 cells are induced to differentiate into neurons, astrocytes and fibroblast-like cells following exposure to retinoic acid (RA). Treatment of the same P19 cells with dimethyl sulfoxide (DMSO) leads to differentiation into mesodermal derivatives, including skeletal and cardiac muscle. Northern blot analysis showed that int-1 RNA was not present in the EC cells but appeared 48 h after RA exposure and could be detected for at least the next 8 days. No int-1 RNA was detected in P19 cells induced to differentiate with DMSO. Nuclear run-on transcription assays showed that int-1 expression in RA-treated P19 cells was induced at the transcriptional level. Immunofluorescent staining with an antibody directed against an int-1 peptide identified immunoreactive material in cytoplasmic granules of fibroblast-like cells in RA-treated P19 cultures. Thus the P19 cell line is a suitable experimental system to study int-1 gene expression and function during neuroectodermal development.

Animals

Expression of the human cardiac actin gene in differentiating rat skeletal myoblasts.

The human cardiac-actin (CH-actin) gene was transfected into rat L6 skeletal myoblasts and stable transformants were isolated. The level of the CH-actin transcript varied between clones but changed little during the differentiation of myoblasts into multinucleate myotubes. Chimeric genes were constructed in which the CH-actin promoter, first non-coding exon (44 bp), and first intron (about 700 bp) were linked to the Herpes simplex virus thymidine kinase (tk) coding region. Clones of L6 cells transformed with these chimeric genes contained variable levels of actin-tk mRNA which changed little during differentiation. Thus, the activity of the CH-actin promoter appeared not to be up-regulated upon differentiation of myoblasts into myotubes. In clones of cells expressing the actin-tk mRNA, the TK protein was not detected in myoblasts but appeared in differentiating multinucleate myotubes. We interpret these results as suggesting developmentally regulated translation of the actin-tk mRNA. Since the first 44 nucleotides of the actin-tk mRNA were derived from the 5'-untranslated region of the CH-actin mRNA. These experiments suggest that translation of the actin-tk mRNA may be controlled by this region.

Actins

AIMS ratings--repeatability.

In the present study, two raters, a psychologist and a nurse, each made five independent ratings of 30 different video-recorded patient-examinations. Having thus excluded patient fluctuation, individual-rater consistency and between-rater agreement over the 6 weeks of the study are examined. While between-rater agreement was apparently being maintained, mean AIMS scores steadily increased. In the hands of these raters, AIMS items 2 and 4 emerged as very reliable, while items 1, 6, and 7 showed high variability. Some patients appeared to be hard to rate. Differences between the study raters and the author JB highlight the issue: how reproducible is an AIMS rating?

Dyskinesia, Drug-Induced

Differentiation and maturation of embryonal carcinoma-derived neurons in cell culture.

We have previously shown that retinoic acid-treated cultures of the P19 line of embryonal carcinoma cells differentiate into neurons, glia, and fibroblast-like cells (Jones-Villeneuve et al., 1982). We report here that the monoclonal antibody HNK-1 reacts with the neurons at a very early stage of their differentiation and is, therefore, an early marker of the neuronal lineage. Cells in differentiated P 19 cultures synthesized acetylcholine but not catecholamines, suggesting that at least some of the neurons are cholinergic. The neurons also carry high-affinity uptake sites for GABA but not for serotonin. In long-term cultures, neuronal processes differentiated into axons and dendrites, which formed synapses. This biological system should prove valuable for examining the development and maturation of cholinergic neurons, since their differentiation occurs in cell culture.

Acetylcholine

Improved separation of multi-locus hypervariable DNA restriction fragments by field inversion gel electrophoresis and fragment detection using a biotinylated probe.

DNA probes to multiple hypervariable human genomic loci are potentially highly informative as regards individual genome identification and parentage studies. However the resultant Southern blot patterns are generally highly complex and their interpretation difficult, with one important limitation being the extent of fragment separation and resolution. The separation of large DNA restriction fragments in agarose gels may be improved, in comparison to separations obtained by conventional electrophoresis, by the use of field inversion techniques. This is demonstrated by the analysis of the complex human Satellite III related DNA polymorphism. Detection of the Satellite III related restriction fragments is achieved either by using a [35S]-labelled probe (228S) or by using the same probe in a convenient non-isotopic form constructed by the photobiotin process. In addition, the probe 228S is useful for sexing the human genome, by the identification of a Y-specific restriction fragment.

Biotin

The role of aggregation in embryonal carcinoma cell differentiation.

Cultures of the P19 line of embryonal carcinoma cells differentiate into various cell types including cardiac muscle when aggregated and exposed to medium containing 1% dimethylsulfoxide (DMSO). DMSO-treated aggregates became completely covered with an epithelial cell type 3 to 4 days following drug exposure. This epithelial cell was tentatively identified as primitive extraembryonic endoderm by its ultrastructural appearance and its possession of cytokeratin intermediate filaments. Muscle cells developed within the interior of DMSO-treated aggregates. They first became apparent 5 to 6 days after DMSO exposure and were characterized by the presence of striated muscle-specific myosin, immature myofibrils, and intercalated discs. We determined the proportion of cells developing into epithelium and muscle in aggregates of various sizes and showed that the proportion of epithelium was highest in small aggregates whereas muscle cells developed only in aggregates of relatively large size. The muscle was usually associated with necrotic areas which developed within the interior of large aggregates. Our results suggest that cardiac muscle differentiation in the aggregates requires both the DMSO-induced formation of an epithelial cell coat and one other condition which may be the proximity to necrotic areas.

Cell Aggregation

Methotrexate (MTX) concentration in tumors following low-dose MTX.

Methotrexate (MTX) is a folate analog competitive with reduced folates for cellular transport and metabolism. Since the normal plasma folate concentration is only 10(-8) M, we tested the possibility that there may be a saturable uptake of MTX by proliferating tumor tissue at plasma MTX concentrations of only 10(-7) to 10(-6) M. Patients with advanced malignancies, refractory to accepted therapy, were given low-dose oral MTX (30-60 mg/m2 total dose in four to eight divided doses). Tumor tissue was biopsied 18-24 h after the last oral dose of MTX. The concentrations of MTX and its polyglutamated derivatives were measured in these samples. Forty-eight percent of the drug in the tumor samples was present as a polyglutamated derivative.

Administration, Oral