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Biomedical subjects

M Graham

Publications and source records attributed to M Graham.

At least 109 records · Page 6Linked to original sources
PubMed1989

Leukemic retinopathy. Relationship between fundus lesions and hematologic parameters at diagnosis.

The authors examined 117 consecutive patients with acute leukemia within a few days of diagnosis. Sixty-six patients had acute nonlymphocytic leukemia, and 51 had acute lymphocytic leukemia. Forty-two percent of the patients had abnormal ocular findings related to leukemia. The authors found an association between the presence of intraretinal hemorrhages and thrombocytopenia for all patients. In addition, patients with acute lymphocytic leukemia and intraretinal hemorrhages had lower hematocrit levels than did those without such hemorrhage. The presence of anemia was related to the findings of white-centered hemorrhages in patients with acute nonlymphocytic leukemia. The presence of cotton-wool spots was not associated with hematologic parameters. Intraretinal hemorrhages, white-centered hemorrhages, and cotton-wool spots were all found more frequently in adults than in children.

Adolescent↗
PubMed1989

Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study.

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Trace element deficiencies in inflammatory bowel disease.

Since the institution of successful parenteral nutrition, much has been learned about malnutrition and the effects and complications of nutritional therapy. A variety of patient groups suffer from malnutrition, and clinicians accept the fact that an extremely high incidence of hospitalized medical and surgical patients are malnourished. Perhaps the group we most frequently see suffering from malnutrition are patients with inflammatory bowel disease (IBD). This is especially true in Crohn's disease, in which a variety of nutritional disturbances have been described.

Humans↗
PubMed1988

RglB facilitated cloning of highly methylated eukaryotic DNA: the human L1 transposon, plant DNA, and DNA methylated in vitro with human DNA methyltransferase.

In vitro methylation of Bluescribe plasmid DNA (pBS) with human placental DNA methyltransferase to 6% 5-methylcytosine (mC) reduced transformation efficiencies in rglB+ host strains C600 and DS410 by almost 2 orders of magnitude. By contrast, the rglB- derivative of DS410 showed no reduction in transformation efficiency with methylation while the rglB- derivative of C600 was partially tolerant to methylation. Further, we show that the 1.8 kilobase (kb) and 1.2 kb KpnI fragments derived from the human L1 repeat have respectively 18.3% and 2.3% mC in vivo. Using these hyper- and hypo-methylated genomic segments ligated into the pBS plasmid, transformants with the highly methylated 1.8 kb L1 insert were recovered at 17 to 40 fold higher frequency with the rglB- host strains than with the rglB+ hosts. In addition, recombinant phage (lambda 2001) containing inserts of plant genomic DNA with 26.7% mC (from Petunia hybrida) when plated on rglB- hosts gave titres up to 222 times higher than on the rglB+ strains.

Cell Line↗
PubMed1988

Ultrasound screening for clinically occult abdominal aortic aneurysm.

In a review of the records of 74 patients who had undergone repair of an abdominal aortic aneurysm at a community hospital between 1977 and 1983 we found that the aneurysm had been undiagnosed before rupture in 35%; these patients had an operative death rate of 50%, whereas elective repair carried a death rate of 4%. The characteristic patient was an obese man over the age of 55 years with hypertension, coronary artery disease, cerebrovascular disease or peripheral vascular disease. Ultrasound examination was performed in 45 patients with these characteristics, and six aneurysms were diagnosed. Either surgery or computed tomography confirmed the diagnosis. The rate of false-negative results was estimated by review of the charts of 100 men over the age of 55 years who had undergone abdominal ultrasonography for other indications: no undetected aneurysms were discovered over 3 years of follow-up. Routine screening in this high-risk group would improve the rate of diagnosis of this potentially fatal condition before rupture and offer the patient the lower mortality rate associated with elective surgery.

Aged↗
PubMed1988

Nevus cell aggregates in the placenta. A histochemical and electron microscopic study.

This is a report of the histochemical and ultrastructural analysis of nevus cell aggregates in the placenta from a neonate with a giant pigmented nevus. Although the distinction between aberrant migration of neural crest elements and blood-borne metastasis from the giant pigmented nevus is not readily resolved, the authors favor the former as an explanation of this unusual placental lesion.

Biopsy↗
PubMed1988

The evolution and outcome of cavitating periventricular leukomalacia in infancy. A study of 46 cases.

Forty six infants with the ultrasonic diagnosis of cavitating periventricular leukomalacia (CPVL) have been reviewed. Follow up examination results allow correlation between the ultrasound appearances and subsequent neurodevelopmental and neurological deficits. The highest incidence of this condition was found in infants at and below 27 weeks gestation, and occurred in 15% of very premature infants surviving 14 days or more. Cavities developed 15 days after the onset of periventricular echodensity (median time). Ventricular dilatation occurred in 24% of the infants who developed cavities. Follow up information was available in 27 infants and 18 of these (67%) had significant neurodevelopmental handicap. The location of echolucent cavities were described as involving anterior, middle or posterior cerebral zones or any combination of these. Cerebral palsy was closely related to the presence of cavities, but there was little association between cavities and developmental delay. Four factors were found to predict cerebral palsy: cavities within the occipital zone, the involvement of multiple regions of the brain, lesions greater than 1 cm in diameter and cavities associated with subcortical leukomalacia. Lesions confined to the anterior or middle zones were unlikely to be associated with significant handicap. The presence of cavities per se was not associated with a higher incidence of severe developmental delay.

Cerebral Palsy↗
PubMed1988

Non-Hodgkin's lymphomas.

The non-Hodgkin's lymphomas are a group of diseases for which substantial progress has been made in understanding tumor biology and effectiveness of treatment during the last few years. These advances may provide insight into the development of neoplasms because of recognized association of lymphomas with viral infections and immunodeficiency. The prognosis for patients with non-Hodgkin's lymphomas continues to improve. As a result, current studies on treatment of lymphomas in certain favorable stages have concentrated on reducing the intensity of therapy. For patients with advanced disease, further improvements in treatment are being sought.

Adolescent↗
PubMed1987

Prediction of cerebral palsy in very low birthweight infants: prospective ultrasound study.

The value of regular cerebral ultrasound scanning in predicting cerebral palsy (CP) was assessed in very low birthweight infants. The infants were scanned before discharge, and their vision and hearing were assessed at age 9 months and neurodevelopment was assessed at 18 months. Ultrasound abnormalities, defined before the study, were periventricular haemorrhage (PVH), "prolonged flare" (echodensity persisting in the periventricular white-matter for more than 2 weeks without cavitating), and cystic periventricular leukomalacia (PVL). The incidence of these three conditions in surviving infants was 49%, 15%, and 8%, respectively. 158 infants survived to be discharged from hospital and 156 had neurodevelopmental assessment at 18 months of corrected age. All infants with PVH alone and confined to the lateral ventricles were normal at follow-up. The presence of cysts accurately predicted abnormal outcome (94%) and was highly specific (96%). Prolonged flare predicted adverse outcome but the accuracy (79%) was less good than for cystic PVL. 12 infants had CP, and 10 of these had ultrasound evidence of PVL. 8 of the 13 infants with cysts had spastic CP. 4 of these were walking independently and had mild CP. No infant with ultrasound evidence of a single cyst or with cysts confined to the frontal region or centrum semiovale had severe CP. Cysts involving the periventricular white-matter in the occipital region were associated with a poor prognosis. Echolucent cystic lesions detected by ultrasound in the neonatal period accurately predict adverse outcome, and if multiple and present in the occipital region, confer a very high risk of severe CP.

Cerebral Hemorrhage↗
PubMed1987

The indirect flight muscle of Drosophila accumulates a unique myosin alkali light chain isoform.

Mapping of the 5' and 3' ends of the Drosophila myosin alkali light chain (MLC-ALK) mRNA by S1 nuclease and primer extension assays has shown that the primary transcripts are identical irrespective of the time in development that the RNA was prepared. As shown by S1 nuclease experiments these transcripts are alternatively spliced in a tissue-specific fashion generating mRNAs that encode tissue-specific protein isoforms. Antibodies were raised to synthetic peptides identical in sequence to the unique portion of each protein. Western blots of one-dimensional polyacrylamide gels using the type-specific antibodies confirmed and extended the results obtained from the S1 nuclease experiments. The indirect flight muscle is the only tissue in the adult that accumulates the alternatively spliced mRNA. The choice between splicing pathways involves the use of a nonconsensus 3' splice junction in larvae and in the tubular muscles of adults, whereas in the indirect flight muscle of the adult only consensus sequences are utilized. The involvement of a trans-acting factor to activate the nonconsensus splice site in the myotubes of larvae and the tubular myotubes of adults is proposed.

Animals↗
PubMed1986

Chromosome 8 breakpoint far 3' of the c-myc oncogene in a Burkitt's lymphoma 2;8 variant translocation is equivalent to the murine pvt-1 locus.

The 2;8 variant translocation of human Burkitt's lymphomas is closely related cytogenetically to the t(6;15) of murine plasmacytomas; both involve a reciprocal exchange between the Ig kappa locus and a band region indistinguishable from that bearing the c-myc oncogene. To define their molecular relationship, we have compared cloned chromosome 8 DNA from the t(2;8) breakpoint in the human Burkitt's lymphoma JBL2 with cloned DNA from the murine pvt-1 locus, the major chromosome 15 breakpoint region in murine t(6;15). DNA sequencing and Southern blot analysis shows that these two regions are homologous. Thus the t(2;8) in JBL2 is the molecular equivalent of many murine t(6;15). The murine pvt-1 locus lies an unknown distance 3' of c-myc; analysis of DNA from several tumours with c-myc amplification reveals that pvt-1 is co-amplified in at least one case, placing pvt-1 approximately 100-500 kb 3' of c-myc. The significance of these results with respect to the role of pvt-1 in tumorigenesis is discussed.

Animals↗
PubMed1986

An inexpensive microcomputer digital imaging system for densitometry: quantitative autoradiography of insulin receptors with 125I and LKB Ultrofilm.

This article describes a video digitizing system designed for measuring film optical density. The system, which is based on a 6-bit (64 gray level) digitizer, solid state video camera, and Apple II microcomputer, digitizes a rectangular area selected by the operator and converts the gray level values into preselected standard units. In order to develop autoradiographic standard curves for quantitative autoradiography with 125I-insulin, liver slices labeled with 125I-insulin and plastic sections containing known amounts of tritium were apposed to the same sheet of LKB Ultrofilm for exposures of 1-7 days. The results indicate that 3H plastic standards can be used to calibrate QAR of 125I-labeled ligands with LKB Ultrofilm. The Apple system was also used to measure binding of 125I-insulin to the external plexiform layer (EPL) in slices of the rat olfactory bulb. Results suggest that the EPL has two binding sites for insulin, a high affinity site with Kd = 1.0 X 10(-8) M and a low affinity site having a Kd = 1.4 X 10(-5) M.

Animals↗
PubMed1986

Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas.

Two loci independently implicated in T-and B-lymphocyte neoplasia are shown to be equivalent. The Mis-1 locus is a common proviral integration site in retrovirally induced rat T lymphomas, while the pvt-1 locus on murine chromosome 15 frequently translocates to the kappa locus in plasmacytomas bearing 6;15 translocations. By comparing cloned sequences, we show that pvt-1 is the murine homolog of Mis-1.

Animals↗
PubMed1985

Variant (6;15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72 kb from the c-myc oncogene.

The variant (6;15) translocations in murine plasmacytomas join the myc oncogene-bearing band of chromosome 15 and the immunoglobulin kappa band of chromosome 6. We recently cloned a region from chromosome 15 linked to C kappa and have now used probes from that region to define the major locus of plasmacytoma variant translocations, which we denote pvt-1. In five of nine plasmacytomas we analysed, the 6;15 translocation resulted from reciprocal recombination between the C kappa locus and a 4.5-kb region of pvt-1. Moreover, nearby we located the region shown by others to have undergone a complex (15;12;6) translocation in plasmacytoma PC7183. All the chromosome 6 breakpoints fell between 1 and 3 kb 5' to C kappa but only two were near J kappa genes. Thus the J kappa -C kappa region appears to be a recombination 'hot spot' in lymphocytes, but the breaks are unlikely to be mediated via V/J recombination enzymes. Comparison of a cloned 108-kb region across pvt-1 and another of 52 kb across c-myc established that the pvt-1 breakpoints lie at least 72 kb from the c-myc promoters. Since c-myc is expressed at a substantial level, the 6;15 translocation apparently activates c-myc. Activation may occur directly, at a remarkable distance along the chromosome, or indirectly, via a putative pvt-1 gene product.

Animals↗
PubMed1985

Diamond-Blackfan syndrome in adult patients.

Two adults with pure red cell aplasia are described. No extrinsic etiologic mechanisms were identified. Evidence of anemia was long-standing and varied in severity. Musculoskeletal abnormalities (webbed neck, Sprengel's and Klippel-Feil deformities, and hand abnormalities) were similar to those seen in the congenital form of red cell aplasia (Diamond-Blackfan syndrome). As in the congenital variety, adrenal cortical steroids resulted in hematologic repair. These observations suggest that congenital (Diamond-Blackfan) pure red cell aplasia may be first recognized in adulthood and that steroids provide a potential therapeutic modality.

Adult↗