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Biomedical subjects

L Simpson

Publications and source records attributed to L Simpson.

At least 181 records · Page 10Linked to original sources
PubMed1983

Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants.

From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. These patients were analyzed in May, 1982, for a minimum follow-up of 14 months. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. For those ANLL patients who underwent BMT while in remission (first, second, and third combined), relapse-free survival is 61% at 1 year compared with 40% for those patients who had their BMT at the time of relapse (greater than or equal to 10% blasts in marrow). On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as greater than 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Patients with ALL who had their BMT cytoreduction at the time of relapse have a survival equal to that of our remission patients, and greater than that of patients in relapse cytoreduced with a single dose as reported by others. However, patients with greater than or equal to 10% blasts have not fared as well, having only a 22% 1 year relapse-free survival compared with a 68% 1 year relapse-free survival for patients with less than 10% blasts. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

Adolescent↗
PubMed1983

Comparison of maxicircle DNAs of Leishmania tarentolae and Trypanosoma brucei.

The conserved portions of the maxicircle DNAs of Leishmania tarentolae and Trypanosoma brucei are organized in a basically colinear manner over a 15- to 17-kilobase region that is interrupted by two small less-homologous sequences. The most highly conserved regions are those encoding the 9S and 12S genes. An approximately 12-kilobase region directly upstream of the 12S gene in the L. tarentolae maxicircle showed no sequence homology with the T. brucei maxicircle and also was not transcribed. An approximately 6-kilobase region in the T. brucei maxicircle in the same relative location also showed no sequence homology with the L. tarentolae maxicircle. We propose that evolution of maxicircle DNA occurs mainly within this "divergent region."

Animals↗
PubMed1983

Evaluation of the chronic hepatic toxicity of 6-mercaptopurine in the wistar rat.

The ability of choline (C) to prevent hepatic toxicity due to chronic administration of 6-mercaptopurine (6-MP) was evaluated in male Wistar rats. Two dose levels of 6-MP and two dose levels of C were used. Choline did not prevent or diminish the hepatic accumulation of triglyceride when administered in combination with 6-MP. The 6-MP did impair the growth of the experimental animals, and this effect was antagonized by C administration. The data provided experimental support for the clinical observation of growth impairment in children treated with chronic antimetabolite therapy for acute lymphoblastic leukemia.

Animals↗
PubMed1983

The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Recovery from aspermia induced by low-dose radiation in seminoma patients.

Gonadal dosimetry and spermatogenic activity was monitored in patients given radiation therapy (RT) after unilateral orchiectomy for seminoma. The RT given was, with minor variations, 3200 rad in 16 fractions in four weeks to the para-aortic and ipsilateral pelvic inguinal lymphatics in order to include the orchiectomy scar. The incidental amount of radiation to the remaining testicle averaged 78.4 +/- 7.4 rad and ranged from 32-178 rad as determined by thermoluminescent dosimetry. Induction of aspermia was documented in ten out of 14 patients who received over 65 rad to the gonad. At lower doses, aspermia may not have occurred or was of short duration. Recovery of sperm in the semen occurred in 12 patients within 30-80 weeks after start of treatment. The data suggest that the time of recovery may be dose dependent within the range of 19-148 rad. During the period of recovery, patients with oligospermic semen may be fertile and should be so advised.

Adult↗
PubMed1982

Transcription of the maxicircle kinetoplast DNA of Leishmania tarentolae.

Numerous transcripts of the 30 kilobase maxicircle component of the kinetoplast DNA of Leishmania Tarentolae have been analyzed by the Northern blotting method. The transcripts range in size from 1.8 to 0.1 kb. RNAs arising from the cloned 6.6 kb region containing the presumptive miniribosomal RNA genes were shown to be transcribed in the direction 12 S to 9 S on the same strand. A preliminary transcriptional map was constructed and related to the distribution of AT-rich regions of the maxicircle DNA molecule.

Adenine↗
PubMed1982

Identification of maxicircle DNA sequences in Leishmania Tarentolae that are homologous to sequences of specific yeast mitochondrial structural genes.

Sequences homologous to the yeast mitochondrial structural genes for cytochrome oxidase subunits I and II, ATPase 6 and cytochrome b were identified on the kinetoplast DNA maxicircle molecule by low stringency hybridization of maxicircle blots with heterologous probes derived from mitochondrial DNA of yeast petite mutants. No hybridization was observed with the yeast ATPase 9 gene probe. The relative extent of base sequence mismatch was determined by melting of the heterologous hybrids. Candidates for the transcripts of these presumptive structural genes were proposed with reference to the transcriptional map of the maxicircle of Leishmania tarentolae. These results provide the first indication that maxicircle DNA specifies information for a limited number of conserved mitochondrial gene products similar to those already described for other eukaryotic cells.

Adenosine Triphosphatases↗
PubMed1982

Long-term survival determinants in Wilms' tumor.

This is a retrospective report of 54 patients with the diagnosis of Wilms' tumor treated at Roswell Park Memorial Institute from 1946 to 1977. The age ranged from 1 month to 57 years with a mean of 7.2 years and a median age of 5 years. An analysis of the survival results showed that patients continued to die of disease until 66 months post-diagnosis, making the 5-year survival a much better evaluation criterion for this group than the traditional 2-year survival. Males fared significantly better in this series (p less than 0.01). This was not due to detectable differences in age group, or histology. While the older age group (more than 15 years old) showed a somewhat better survival outlook for the first 2 years post-diagnosis, this difference became negligible at 5 years post-diagnosis.

Adolescent↗
PubMed1982

Isolation and characterization of drug resistant mutants of Crithidia fasciculata.

Mutants of Crithidia fasciculata, resistant to Actinomycin D, Tubercidin, Crystal Violet, 6-Azauridine, and 5-Fluorouracil were obtained and characterized. The mutants were stable when maintained under nonselective conditions, and could be grouped in several subclasses on the basis of cross-resistance to other drugs. Actinomycin D- and Crystal Violet-resistant mutants appeared spontaneously whereas the others appeared only after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Analysis with a cell sorter indicated no large scale meiotic changes in ploidy under the various culture conditions employed. These mutants may provide suitable, selectable, genetic markers for use in studying the possibility of a sexual mating process in Crithidia.

Animals↗
PubMed1982

Erythrocytapheresis (red cell exchange).

Automated erythrocytapheresis (red cell exchange) was performed on two patients with sickle cell disease using the IBM 2997 Blood Cell Separator. Preoperative red cell exchange was performed on patient L.N. to prevent possible anterior ischemic syndrome during surgery. A red cell exchange procedure on patient A.Y. diminished her acute sickle crisis symptoms and resolved respiratory complications. For each patient, the instrument settings were varied in order to achieve the desired effect for the hematological needs of the individual patient.

Acute Disease↗
PubMed1980

Kinetoplast DNA and RNA of Trypanosoma brucei.

Kinetoplast DNA (kDNA) and kinetoplast RNA (kRNA) were isolated from bloodstream and procyclic culture forms of two clonal strains of Trypanosoma brucei. No differences were observed in kDNA (maxicircle) restriction profiles between bloodstream or procyclic culture forms of the same strain. Some differences were observed in kDNA maxicircle restriction sites between the two strains. Buoyant density analysis of Pst I digested kDNA showed the release of a minor low density band representing unit length linearized maxicircle DNA. Pst I or Bam H1-linearized maxicircle DNA was isolated by the Hoechst 33258 dye--CsCl method and a restriction enzyme map of the maxicircle was constructed. Closed monomeric minicircles released from kDNA networks by sonication sedimented with a molecular size of around 1100 base pairs. A substantial minor length heterogeneity was evident in acrylamide gel electrophoresis of once cut minicircles. Several minicircle sequence classes and two Hind III maxicircle fragments representing approx. 50% of the maxicircle were cloned in the bacterial plasmid, pBR322, in Escherichia coli. A purified kinetoplast-mitochondrion fraction was isolated from procyclic culture forms by the Renografin flotation method. The major kRNA components were two small RNAs which comigrated with Leishmania tarentolae 9 and 12 S kRNAs in denaturing gels. These RNAs hybridized to the maxicircle component of the kDNA, specifically to the smaller cloned Hind III maxicircle fragment. This cloned fragment had substantial sequence homology with the cloned maxicircle fragment from L. tarentolae which contains the 9 and 12 S RNA genes, implying an evolutionary conservation of the 9 and 12 S gene sequences. Identical kRnAs were observed in cultured bloodstream forms of T. brucei.

Animals↗
PubMed1980

Strains and clones of Trypanosoma cruzi can be characterized by pattern of restriction endonuclease products of kinetoplast DNA minicircles.

A simple method was developed for the characterization of different strains of Trypanosoma cruzi. T. cruzi stocks isolated from vectors or by hemoculture from patients with Chagas disease could be grouped in subpopulations having similar patterns of restriction endonuclease products of kinetoplast DNA minicircles. We designate such subpopulations by the term "schizodemes." Furthermore, it is shown that, from a given T. cruzi strain, clones with different biological properties can be isolated and identified by their restriction patterns.

Animals↗
PubMed1980

The kinetoplast DNA of the hemoflagellate protozoa.

The kinetoplast DNA of Leishmania tarentolae and Trypanosoma brucei was studied in terms of genetic organization and transcriptional activity. Several minor sequence classes of minicircles from L. tarentolae were cloned in a bacterial plasmid and were compared in terms of sequence organization. The cloned minicircles were characterized by the possession of a constant region of at least 91 nucleotides and a variable region. Minicircles from Trypanosoma brucei strain 366D were also cloned. Fragments of the maxicircle DNA from both species were also cloned in pBR322. No homology with the cloned minicircles was apparent. Several maxicircle transcripts, in addition to the 9 and 12s presumptive ribosomal RNAs, were observed in L. tarentolae. The 9 and 12s RNA genes were also mapped on the T. brucei maxicircle. Sequence homology between the L. tarentolae 9 and 12s RNA genes and the T. brucei 9 and 12s RNA genes was observed. A culture system was developed to study the developmental change of cultured bloodstream forms of T. brucei into procyclic forms. This developmental system is amenable for the study of the role of the kinetoplast DNA in the extensive mitochondrial biogenesis that occurs at this time.

Animals↗